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Evaluating the Safety and Tolerability of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • HIV-1 infection
  • CD4+ T cell count greater than 350 cells/mm^3 within 45 days prior to study entry
  • Documented virologic suppression defined as HIV-1 RNA level below the limit of quantification (eg, less than 40, less than 50, or less than 75 copies/mL, depending on the assay) using an FDA-approved assay with a quantification limit of 75 copies/mL or lower for at least 48 weeks prior to study entry
  • Screening HIV-1 RNA level below the limit of quantification
  • Tuberculosis (TB) screening within 365 days of the screening visit diagnosed by tuberculin skin test or interferon gamma release assay
  • Currently on continuous ART for at least 730 days prior to study entry, defined as continuous ART for the 730 days period, inclusive, prior to study entry with no ART interruption longer than 7 consecutive days. NOTE: The current regimen must include TDF/FTC, TAF/FTC, TDF+3TC, or ABC/3TC; plus a nonnucleoside reverse transcriptase inhibitor or integrase strand transfer inhibitor (NNRTI or INSTI, not containing cobicistat) for at least 60 days, inclusive, prior to study entry.

  • The following laboratory values obtained within 45 days prior to entry:

    • Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3
    • Hemoglobin greater than 12.0 g/dL for men and greater than 11.0 g/dL for women
    • Platelets greater than or equal to 140,000/mm^3
    • Calculated creatinine clearance (CrCl) greater than or equal to 70 mL/min (by Cockcroft Gault equation)
    • Aspartate aminotransferase (AST) (SGOT) less than or equal to 1.5x upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) (SGPT) less than or equal to 1.5x ULN
    • Alkaline phosphatase less than or equal to 1.5x ULN
  • For females of reproductive potential, a negative serum or urine pregnancy test with a sensitivity of 25 mIU/mL within 72 hours, inclusive, prior to study entry
  • All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization)
  • All participants of reproductive potential, who were participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception while receiving the study drugs and for 7 weeks after stopping the medications
  • Ability and willingness of participant or legal representative to provide written informed consent and attend study visits as scheduled at a participating site

Exclusion Criteria:

  • A current or past history of progressive multifocal leukoencephalopathy
  • Breastfeeding or pregnancy
  • Use of strong inhibitors or inducers of CYP3A4 including a protease inhibitor, cobicistat or entry inhibitors as part of the current ART regimen or other concomitant therapy
  • Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Acute or serious illness or infection requiring systemic treatment and/or hospitalization within 60 days prior to entry
  • Vaccinations (other than influenza) less than or equal to 45 days prior to the study entry visit.
  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy or investigational therapy less than or equal to 60 days prior to study entry

  • Any current diagnosis or past history of a significant cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, neuropsychiatric, psychiatric, or other serious illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data or affect the participant's ability to participate in the study. Diagnoses that would lead to exclusion include, but were not limited to the following:

    • CDC category C AIDS-indicator conditions
    • NOTE A: Except HIV encephalopathy, HIV wasting, esophageal candidiasis, or pneumocystis pneumonia without dissemination.
    • NOTE B: List available: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm
    • Herpes zoster (dermatomal or non-dermatomal).
    • NOTE C: A history of prior chickenpox was not exclusionary.
    • Lymphoproliferative malignancy
    • Chronic liver disease of any etiology and any degree of severity
    • Chronic hepatitis, except for hepatitis C that has been cured (defined as a Sustained Virologic Response, which is an undetectable HCV-RNA at 12 weeks or more after completing treatment measured by a sensitive, qualitative, or quantitative HCV-RNA assay)
    • Disseminated fungal infection of any type or duration that is not limited to cutaneous or mucocutaneous surfaces
    • A medical disorder that predisposes to bleeding
  • Change in the ART regimen within 12 weeks, inclusive, prior to study entry or intended modification of ART during the study.
  • History of untreated latent tuberculosis infection (LTBI) diagnosed by tuberculin skin test or interferon gamma release assay. LTBI treatment would consist of 9 months of isoniazid or an equivalent therapy completed at least 4 weeks prior to study entry.

Sites / Locations

  • Alabama CRS
  • UCLA CARE Center CRS
  • UCSD Antiviral Research Center CRS
  • Ucsf Hiv/Aids Crs
  • Northwestern University CRS
  • Washington University Therapeutics (WT) CRS
  • Weill Cornell Chelsea CRS
  • Weill Cornell Uptown CRS
  • University of Rochester Adult HIV Therapeutic Strategies Network CRS
  • Cincinnati Clinical Research Site
  • Case Clinical Research Site
  • Penn Therapeutics, CRS
  • The Miriam Hospital Clinical Research Site (TMH CRS) CRS
  • Vanderbilt Therapeutics (VT) CRS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Arm A: Ruxolitinib

Arm B: No Study Treatment

Arm Description

Participants received ruxolitinib twice a day for 5 weeks. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.

Participants did not receive any study treatment. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.

Outcomes

Primary Outcome Measures

Percentage of Participants on the Ruxolitinib Arm Who Experienced Any Safety Milestone Events While On-Treatment
Events defined as safety milestones are listed below and together makeup the composite endpoint. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Discontinuation of Ruxolitinib due to thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity related to study drug Percent experiencing a safety milestone will be reported.
Percentage of Participants Who Experienced Any Safety Milestones On-study From Entry to Week 5
Events defined as safety milestones are listed below and together makeup the composite endpoint. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Occurrence of Grade 2 or higher thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing a safety milestone will be reported.
Percentage of Participants Who Experienced Each Safety Milestone That Occurred On-study From Entry to Week 5
Events defined as safety milestones are listed below. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Occurrence of Grade 2 or higher thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing each safety milestone will be reported. Safety milestone categories are not mutually exclusive.
Number of Participants With Premature Discontinuation of Study Treatment in the Ruxolitinib Arm
Number of participants with premature discontinuation of study treatment are summarized.
Fold Change in the Level of Plasma Interleukin 6 (IL-6) From Baseline to Week 4/5
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Fold change was calculated as the value at Week 4/5 divided by the value at Baseline.

Secondary Outcome Measures

Percentage of Participants on the Ruxolitinib Arm Who Experienced Any Safety Milestone Events During Total Follow-up
Events defined as safety milestones are listed below and together makeup the composite endpoint. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Discontinuation of Ruxolitinib due to thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity related to study drug Percent experiencing a safety milestone will be reported.
Percentage of Participants Who Experienced Any Safety Milestones On-study From Entry to Week 12
Events defined as safety milestones are listed below and together makeup the composite endpoint. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Occurrence of Grade 2 or higher thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing a safety milestone will be reported.
Percentage of Participants Who Experienced Each Safety Milestone That Occurred On-study From Entry to Week 12
Events defined as safety milestones are listed below. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm3 (for participants with entry CD4+ T cell count < 700 cells/mm3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Occurrence of Grade 2 or higher thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing each safety milestone will be reported. Safety milestone categories are not mutually exclusive.
Number of Participants Who Experienced a Protocol-defined Reportable Adverse Event at Any Post-entry Time Point.
Protocol-defined reportable adverse events include: all diagnoses regardless of grade, Grade 3 or higher sign/symptoms or laboratory values, any signs/symptoms or laboratory values that led to a change in treatment or met ICH, EAE, or SAE guidelines. See the Protocol Section References for links to the EAE manual. This is a subset of the events reported in the Adverse Events section.
Creatinine Clearance
Creatinine clearance was calculated using the Cockcroft Gault equation. The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Change in Creatinine Clearance Values From Entry
Creatinine clearance was calculated using the Cockcroft Gault equation. The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Creatinine
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Change in Creatinine Values From Entry
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Absolute Neutrophil Count (ANC)
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Change in Absolute Neutrophil Count (ANC) Values From Entry
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Hemoglobin
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Change in Hemoglobin Values From Entry
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Platelet Count
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Change in Platelet Counts From Entry
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Aspartate Aminotransferase (AST) (SGOT)
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Change in Aspartate Aminotransferase (AST) (SGOT) Values From Entry
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Alanine Aminotransferase (ALT) (SGPT)
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Change in Alanine Aminotransferase (ALT) (SGPT) Values From Entry
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Fold Change in the Level of Plasma Interleukin 6 (IL-6)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Week 10/12 is defined as the geometric mean of the Week 10 and Week 12 values. Fold change was calculated as the value at Week 10/12 divided by the value at Baseline and the value at Week 4/5 divided by the value at Week 10/12.
Fold Change in the Level of Soluble CD14 (sCD14)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Fold change was calculated as the value at Week 4/5 divided by the value at Baseline, the value at Week 12 divided by the value at Baseline, and the value at Week 12 divided by the value at Week 4/5.
Change in CD4+ T Cell Count
Baseline is defined as the average of pre-entry and entry. Absolute change was calculated as the value at Week 2 minus the value at Baseline, the value at week 5 minus the value at baseline, the value at week 12 minus the value at baseline, and the value at week 5 minus the value at week 12.
Number of Participants With Plasma HIV-1 RNA Level Above the Limit of Quantification
Participants were required to be virally suppressed, with a plasma HIV-1 RNA level below 40 copies/mL. The number of participants with plasma HIV-1 RNA level above the limit of quantification is reported at each time point.
Relative Risks of HIV-1 RNA by Single Copy Assay (SCA) < 0.4 Copies/mL
HIV-1 RNA was measured via Single Copy Assay Using Primer in Integrase (iSCA), results were reported as below or above the assay limit of detection (LOD) (LOD = 0.4 copies/mL). GEE models for binary data were used to calculate the relative risk of having HIV-1 RNA by iSCA <0.4 copies/mL (Week 5 compared to Entry, Week 12 compared to Entry, and Week 12 compared to Week 5).
Fold Change in the Level of Plasma Tumor Necrosis Factor Alpha (TNF Alpha)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in the Level of Plasma Interleukin 1 Beta (IL-1 Beta)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in the Level of Plasma Interleukin 7 (IL-7)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in the Level of Interleukin 1 Alpha (IL-1 Alpha)
Laboratory testing was not performed so the data are not available.
Fold Change in the Level of Interferon Gamma-induced Protein 10 (IP-10)
Laboratory testing was not performed so the data are not available.
Fold Change in the Level of Macrophage Colony-stimulating Factor
Laboratory testing was not performed so the data are not available.
Fold Change in the Level of Neopterin
Data not available because the testing lab reported that the values were unreliable.
Fold Change in the Level of Plasma Interleukin 10 (IL-10)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in the Level of Plasma Interleukin 15 (IL-15)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in the Level of Plasma Interleukin 18 (IL-18)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in the Level of Plasma Transforming Growth Factor Beta 1 (TGF Beta-1)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in the Level of Plasma Transforming Growth Factor Beta 2 (TGF Beta-2)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in the Level of Plasma Transforming Growth Factor Beta 3 (TGF Beta-3)
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Change in (CD3+CD4+) CD38+HLADR+
Absolute change in the percent of parent cells (CD4+) that express CD38+HLADR+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD8+) CD38+HLADR+
Absolute change in the percent of parent cells (CD8+) that express CD38+HLADR+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD4+) CD25hi+
Absolute change in the percent of parent cells (CD4+) that express CD25hi+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD8+) CD25+
Absolute change in the percent of parent cells (CD8+) that express CD25+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD4+) CD127+
Absolute change in the percent of parent cells (CD4+) that express CD127+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD8+) CD127+
Absolute change in the percent of parent cells (CD8+) that express CD127+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD4+) Ki67+
Absolute change in the percent of parent cells (CD4+) that express Ki67+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD8+) Ki67+
Absolute change in the percent of parent cells (CD8+) that express Ki67+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD4+) Bcl2+
Absolute change in the percent of parent cells (CD4+) that express Bcl2+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD8+) Bcl2+
Absolute change in the percent of parent cells (CD8+) that express Bcl2+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD4+) a4b7+
Absolute change in the percent of parent cells (CD4+) that express a4b7+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD8+) a4b7+
Absolute change in the percent of parent cells (CD8+) that express a4b7+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD4+) CX3CR1+
Absolute change in the percent of parent cells (CD4+) that express CX3CR1+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in (CD3+CD8+) CX3CR1+
Absolute change in the percent of parent cells (CD8+) that express CX3CR1+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in CD69
Data not available because the team decided they were no longer clinically relevant, so samples were not tested for CD69.
Change in PAR-1
Data not available because the team decided they were no longer clinically relevant, so samples were not tested for PAR-1.
Change in Classical Monocytes (CD14+CD16-)
Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Classical Monocytes (CD14+CD16-) Expressing CD163+
Absolute change in the percent of classical monocytes (CD14+CD16-) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Classical Monocytes (CD14+CD16-) Expressing CCR2+
Absolute change in the percent of classical monocytes (CD14+CD16-) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Classical Monocytes (CD14+CD16-) Expressing CX3CR1+
Absolute change in the percent of classical monocytes (CD14+CD16-) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Inflammatory Monocytes (CD14+CD16+)
Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CD163+
Absolute change in the percent of inflammatory monocytes (CD14+CD16-) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CCR2+
Absolute change in the percent of inflammatory monocytes (CD14+CD16+) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CX3CR1+
Absolute change in the percent of inflammatory monocytes (CD14+CD16+) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Patrolling Monocytes (CD14dimCD16+)
Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CD163+
Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CCR2+
Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CX3CR1+
Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Fold Change in Cellular HIV-1 DNA
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Fold Change in Cellular HIV-1 Total RNA
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Percentage of Participants With Detectable CMV Shedding
Level of CMV shedding was summarized by study week and arm as the percentage of those above and below the assay limit of detection. Detectable CMV shedding was defined as CMV level > 0 copies/ml of elution. The percentage of participants with detectable CMV at any on-treatment time point (ever shedding at weeks 1, 2, 4, or 5) and any post-treatment time point (ever shedding at weeks 10 or 12) was contrasted between study arms.
Ruxolitinib Systemic Clearance (CL/F) From 2-compartment Pharmacokinetic (PK)
Ruxolitinib plasma concentrations were fitted to a population 2-compartment distribution model, assuming first-order input, distribution and elimination from the plasma compartment, using nonlinear mixed-effects modeling software. We estimated parameter geometric means and proportional variabilities between subjects (IIV when feasible) and the variability in drug absorption between occasions (IOV week 1 and week 4/5), and related distribution volumes to body weight.

Full Information

First Posted
June 16, 2015
Last Updated
November 2, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT02475655
Brief Title
Evaluating the Safety and Tolerability of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults
Official Title
A Randomized, Pilot Study of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
May 16, 2016 (Actual)
Primary Completion Date
February 18, 2018 (Actual)
Study Completion Date
April 4, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study was to evaluate the safety and tolerability of ruxolitinib in HIV-positive adults who were virologically suppressed and who were on antiretroviral therapy (ART).
Detailed Description
Ruxolitinib is a medication approved by the U.S. Food and Drug Administration (FDA) to treat myelofibrosis, a disorder in which bone marrow is replaced by scar (fibrosis) tissue. Many of the cytokines affected by myelofibrosis are also affected by HIV. Because of this, ruxolitinib may also be a possible treatment for HIV. The purpose of this study was to evaluate the safety and tolerability of ruxolitinib in HIV-positive adults who were on ART and who were virologically suppressed. Researchers evaluated the effect ruxolitinib had on inflammation and immune activation. This study enrolled HIV-positive adults who were on select ART regimens and who had viral suppression. ART was not provided by the study; participants continued to receive ART from their own health care providers. Participants were randomly assigned to receive either ruxolitinib (Arm A) or no study treatment (Arm B) in 2:1 ratio. Participants in Arm A received ruxolitinib twice a day for 5 weeks. All participants attended study visits at entry (Day 0) and Weeks 1, 2, 4, 5, 10, and 12. These visits included physical examinations, clinical assessments, blood collection, adherence assessments, oral swab collection, and pregnancy testing for female participants. At Weeks 1 and 4, participants in Arm A took part in pharmacokinetic (PK) sampling, which involved having blood drawn several times over 6 to 8 hours.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Ruxolitinib
Arm Type
Experimental
Arm Description
Participants received ruxolitinib twice a day for 5 weeks. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.
Arm Title
Arm B: No Study Treatment
Arm Type
No Intervention
Arm Description
Participants did not receive any study treatment. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Intervention Description
10 mg orally twice daily for 5 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants on the Ruxolitinib Arm Who Experienced Any Safety Milestone Events While On-Treatment
Description
Events defined as safety milestones are listed below and together makeup the composite endpoint. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Discontinuation of Ruxolitinib due to thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity related to study drug Percent experiencing a safety milestone will be reported.
Time Frame
Entry to Week 5
Title
Percentage of Participants Who Experienced Any Safety Milestones On-study From Entry to Week 5
Description
Events defined as safety milestones are listed below and together makeup the composite endpoint. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Occurrence of Grade 2 or higher thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing a safety milestone will be reported.
Time Frame
Entry to Week 5
Title
Percentage of Participants Who Experienced Each Safety Milestone That Occurred On-study From Entry to Week 5
Description
Events defined as safety milestones are listed below. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Occurrence of Grade 2 or higher thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing each safety milestone will be reported. Safety milestone categories are not mutually exclusive.
Time Frame
Entry to Week 5
Title
Number of Participants With Premature Discontinuation of Study Treatment in the Ruxolitinib Arm
Description
Number of participants with premature discontinuation of study treatment are summarized.
Time Frame
Entry to Week 5
Title
Fold Change in the Level of Plasma Interleukin 6 (IL-6) From Baseline to Week 4/5
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Fold change was calculated as the value at Week 4/5 divided by the value at Baseline.
Time Frame
Pre-entry, Entry, Weeks 4 and 5
Secondary Outcome Measure Information:
Title
Percentage of Participants on the Ruxolitinib Arm Who Experienced Any Safety Milestone Events During Total Follow-up
Description
Events defined as safety milestones are listed below and together makeup the composite endpoint. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Discontinuation of Ruxolitinib due to thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity related to study drug Percent experiencing a safety milestone will be reported.
Time Frame
Entry to Week 12
Title
Percentage of Participants Who Experienced Any Safety Milestones On-study From Entry to Week 12
Description
Events defined as safety milestones are listed below and together makeup the composite endpoint. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm^3 (for participants with entry CD4+ T cell count < 700 cells/mm^3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm^3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Occurrence of Grade 2 or higher thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing a safety milestone will be reported.
Time Frame
Entry to Week 12
Title
Percentage of Participants Who Experienced Each Safety Milestone That Occurred On-study From Entry to Week 12
Description
Events defined as safety milestones are listed below. Confirmed CD4+ decline > 33% of entry and to < 350 cell/mm3 (for participants with entry CD4+ T cell count < 700 cells/mm3) Confirmed CD4+ decline > 50% of entry (for participants with entry CD4+ T cell count ≥ 700 cells/mm3) Confirmed HIV-1 RNA level above the lower limit of quantification in the absence of an interruption of ART New or recurrent CDC category C AIDS-indicator condition HIV-1 associated infection including Herpes zoster Lymphoproliferative malignancies Grade 4 or recurrence of Grade 3 anemia/neutropenia New diagnosis of pneumonia, sepsis, or bacteremia Occurrence of Grade 2 or higher thrombocytopenia Any Grade 4 or recurrence of Grade 3 toxicity Percent experiencing each safety milestone will be reported. Safety milestone categories are not mutually exclusive.
Time Frame
Entry to Week 12
Title
Number of Participants Who Experienced a Protocol-defined Reportable Adverse Event at Any Post-entry Time Point.
Description
Protocol-defined reportable adverse events include: all diagnoses regardless of grade, Grade 3 or higher sign/symptoms or laboratory values, any signs/symptoms or laboratory values that led to a change in treatment or met ICH, EAE, or SAE guidelines. See the Protocol Section References for links to the EAE manual. This is a subset of the events reported in the Adverse Events section.
Time Frame
Entry to Week 12
Title
Creatinine Clearance
Description
Creatinine clearance was calculated using the Cockcroft Gault equation. The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Change in Creatinine Clearance Values From Entry
Description
Creatinine clearance was calculated using the Cockcroft Gault equation. The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Creatinine
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Change in Creatinine Values From Entry
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Absolute Neutrophil Count (ANC)
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Change in Absolute Neutrophil Count (ANC) Values From Entry
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Hemoglobin
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Change in Hemoglobin Values From Entry
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Platelet Count
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Change in Platelet Counts From Entry
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Aspartate Aminotransferase (AST) (SGOT)
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Change in Aspartate Aminotransferase (AST) (SGOT) Values From Entry
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Alanine Aminotransferase (ALT) (SGPT)
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Change in Alanine Aminotransferase (ALT) (SGPT) Values From Entry
Description
The arithmetic mean for each participant was calculated at week 1 and week 2 combined, week 4 and week 5 combined, and week 10 and week 12 combined. Absolute change was calculated as the value at Week 1/2 minus the value at Entry, the value at Week 4/5 minus the value at Entry, and the value at Week 10/12 minus the value at Entry.
Time Frame
Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Fold Change in the Level of Plasma Interleukin 6 (IL-6)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Week 10/12 is defined as the geometric mean of the Week 10 and Week 12 values. Fold change was calculated as the value at Week 10/12 divided by the value at Baseline and the value at Week 4/5 divided by the value at Week 10/12.
Time Frame
Pre-entry, Entry, Weeks 4, 5, 10 and 12
Title
Fold Change in the Level of Soluble CD14 (sCD14)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Baseline is defined as the geometric mean of the Pre-entry and Entry values. Week 4/5 is defined as the geometric mean of the Week 4 and Week 5 values. Fold change was calculated as the value at Week 4/5 divided by the value at Baseline, the value at Week 12 divided by the value at Baseline, and the value at Week 12 divided by the value at Week 4/5.
Time Frame
Pre-entry, Entry, Weeks 4, 5, and 12
Title
Change in CD4+ T Cell Count
Description
Baseline is defined as the average of pre-entry and entry. Absolute change was calculated as the value at Week 2 minus the value at Baseline, the value at week 5 minus the value at baseline, the value at week 12 minus the value at baseline, and the value at week 5 minus the value at week 12.
Time Frame
Pre-entry, Entry, Weeks 2, 5, and 12
Title
Number of Participants With Plasma HIV-1 RNA Level Above the Limit of Quantification
Description
Participants were required to be virally suppressed, with a plasma HIV-1 RNA level below 40 copies/mL. The number of participants with plasma HIV-1 RNA level above the limit of quantification is reported at each time point.
Time Frame
Entry, Weeks 2, 5, and 12
Title
Relative Risks of HIV-1 RNA by Single Copy Assay (SCA) < 0.4 Copies/mL
Description
HIV-1 RNA was measured via Single Copy Assay Using Primer in Integrase (iSCA), results were reported as below or above the assay limit of detection (LOD) (LOD = 0.4 copies/mL). GEE models for binary data were used to calculate the relative risk of having HIV-1 RNA by iSCA <0.4 copies/mL (Week 5 compared to Entry, Week 12 compared to Entry, and Week 12 compared to Week 5).
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Plasma Tumor Necrosis Factor Alpha (TNF Alpha)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Plasma Interleukin 1 Beta (IL-1 Beta)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Plasma Interleukin 7 (IL-7)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Interleukin 1 Alpha (IL-1 Alpha)
Description
Laboratory testing was not performed so the data are not available.
Time Frame
Pre-entry, Entry, Weeks 4, 5, and 12
Title
Fold Change in the Level of Interferon Gamma-induced Protein 10 (IP-10)
Description
Laboratory testing was not performed so the data are not available.
Time Frame
Pre-entry, Entry, Weeks 4, 5, and 12
Title
Fold Change in the Level of Macrophage Colony-stimulating Factor
Description
Laboratory testing was not performed so the data are not available.
Time Frame
Pre-entry, Entry, Weeks 4, 5, and 12
Title
Fold Change in the Level of Neopterin
Description
Data not available because the testing lab reported that the values were unreliable.
Time Frame
Pre-entry, Entry, Weeks 4, 5, and 12
Title
Fold Change in the Level of Plasma Interleukin 10 (IL-10)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Plasma Interleukin 15 (IL-15)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Plasma Interleukin 18 (IL-18)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Plasma Transforming Growth Factor Beta 1 (TGF Beta-1)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Plasma Transforming Growth Factor Beta 2 (TGF Beta-2)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in the Level of Plasma Transforming Growth Factor Beta 3 (TGF Beta-3)
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD4+) CD38+HLADR+
Description
Absolute change in the percent of parent cells (CD4+) that express CD38+HLADR+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD8+) CD38+HLADR+
Description
Absolute change in the percent of parent cells (CD8+) that express CD38+HLADR+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD4+) CD25hi+
Description
Absolute change in the percent of parent cells (CD4+) that express CD25hi+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD8+) CD25+
Description
Absolute change in the percent of parent cells (CD8+) that express CD25+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD4+) CD127+
Description
Absolute change in the percent of parent cells (CD4+) that express CD127+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD8+) CD127+
Description
Absolute change in the percent of parent cells (CD8+) that express CD127+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD4+) Ki67+
Description
Absolute change in the percent of parent cells (CD4+) that express Ki67+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD8+) Ki67+
Description
Absolute change in the percent of parent cells (CD8+) that express Ki67+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD4+) Bcl2+
Description
Absolute change in the percent of parent cells (CD4+) that express Bcl2+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD8+) Bcl2+
Description
Absolute change in the percent of parent cells (CD8+) that express Bcl2+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD4+) a4b7+
Description
Absolute change in the percent of parent cells (CD4+) that express a4b7+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD8+) a4b7+
Description
Absolute change in the percent of parent cells (CD8+) that express a4b7+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD4+) CX3CR1+
Description
Absolute change in the percent of parent cells (CD4+) that express CX3CR1+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in (CD3+CD8+) CX3CR1+
Description
Absolute change in the percent of parent cells (CD8+) that express CX3CR1+ cells (cellular marker of immune activation and inflammation in the peripheral blood). Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in CD69
Description
Data not available because the team decided they were no longer clinically relevant, so samples were not tested for CD69.
Time Frame
Entry, Weeks 5 and 12
Title
Change in PAR-1
Description
Data not available because the team decided they were no longer clinically relevant, so samples were not tested for PAR-1.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Classical Monocytes (CD14+CD16-)
Description
Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Classical Monocytes (CD14+CD16-) Expressing CD163+
Description
Absolute change in the percent of classical monocytes (CD14+CD16-) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Classical Monocytes (CD14+CD16-) Expressing CCR2+
Description
Absolute change in the percent of classical monocytes (CD14+CD16-) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Classical Monocytes (CD14+CD16-) Expressing CX3CR1+
Description
Absolute change in the percent of classical monocytes (CD14+CD16-) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Inflammatory Monocytes (CD14+CD16+)
Description
Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CD163+
Description
Absolute change in the percent of inflammatory monocytes (CD14+CD16-) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CCR2+
Description
Absolute change in the percent of inflammatory monocytes (CD14+CD16+) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Inflammatory Monocytes (CD14+CD16+) Expressing CX3CR1+
Description
Absolute change in the percent of inflammatory monocytes (CD14+CD16+) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Patrolling Monocytes (CD14dimCD16+)
Description
Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CD163+
Description
Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CD163+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CCR2+
Description
Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CCR2+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Change in Patrolling Monocytes (CD14dimCD16+) Expressing CX3CR1+
Description
Absolute change in the percent of patrolling monocytes (CD14dimCD16+) that express CX3CR1+. Absolute change was calculated as the value at week 5 minus the value at entry, and the value at week 12 minus the value at entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in Cellular HIV-1 DNA
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Fold Change in Cellular HIV-1 Total RNA
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12
Title
Percentage of Participants With Detectable CMV Shedding
Description
Level of CMV shedding was summarized by study week and arm as the percentage of those above and below the assay limit of detection. Detectable CMV shedding was defined as CMV level > 0 copies/ml of elution. The percentage of participants with detectable CMV at any on-treatment time point (ever shedding at weeks 1, 2, 4, or 5) and any post-treatment time point (ever shedding at weeks 10 or 12) was contrasted between study arms.
Time Frame
Pre-entry, Entry, and Weeks 1, 2, 4, 5, 10, and 12
Title
Ruxolitinib Systemic Clearance (CL/F) From 2-compartment Pharmacokinetic (PK)
Description
Ruxolitinib plasma concentrations were fitted to a population 2-compartment distribution model, assuming first-order input, distribution and elimination from the plasma compartment, using nonlinear mixed-effects modeling software. We estimated parameter geometric means and proportional variabilities between subjects (IIV when feasible) and the variability in drug absorption between occasions (IOV week 1 and week 4/5), and related distribution volumes to body weight.
Time Frame
Week 1 and, Week 4/5; blood samples were drawn pre-dose and at 1-1.5, 2.5-4, 4-6, and 6-8 hours post-dosing
Other Pre-specified Outcome Measures:
Title
Change in 2 Long-terminal Repeat Sequences [LTRs]
Description
Data not available because all values were below assay limit.
Time Frame
Entry, Week 5, and Week 12
Title
Level of HHV Shedding (EBV, HSV, HHV-6, HHV-7, and HHV-8)
Description
Data not available because no samples were collected to test for these measures as the team decided they were no longer clinically relevant.
Time Frame
Pre-entry, Entry, Weeks 1, 2, 4, 5, 10, and 12
Title
Fold Change in Integrated DNA
Description
All values were log10 transformed prior to calculating change and conducting analyses and back transformed for presentation. Fold change was calculated as the value at Week 5 divided by the value at Entry and the value at Week 12 divided by the value at Entry.
Time Frame
Entry, Weeks 5 and 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: HIV-1 infection CD4+ T cell count greater than 350 cells/mm^3 within 45 days prior to study entry Documented virologic suppression defined as HIV-1 RNA level below the limit of quantification (eg, less than 40, less than 50, or less than 75 copies/mL, depending on the assay) using an FDA-approved assay with a quantification limit of 75 copies/mL or lower for at least 48 weeks prior to study entry Screening HIV-1 RNA level below the limit of quantification Tuberculosis (TB) screening within 365 days of the screening visit diagnosed by tuberculin skin test or interferon gamma release assay Currently on continuous ART for at least 730 days prior to study entry, defined as continuous ART for the 730 days period, inclusive, prior to study entry with no ART interruption longer than 7 consecutive days. NOTE: The current regimen must include TDF/FTC, TAF/FTC, TDF+3TC, or ABC/3TC; plus a nonnucleoside reverse transcriptase inhibitor or integrase strand transfer inhibitor (NNRTI or INSTI, not containing cobicistat) for at least 60 days, inclusive, prior to study entry. The following laboratory values obtained within 45 days prior to entry: Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3 Hemoglobin greater than 12.0 g/dL for men and greater than 11.0 g/dL for women Platelets greater than or equal to 140,000/mm^3 Calculated creatinine clearance (CrCl) greater than or equal to 70 mL/min (by Cockcroft Gault equation) Aspartate aminotransferase (AST) (SGOT) less than or equal to 1.5x upper limit of normal (ULN) Alanine aminotransferase (ALT) (SGPT) less than or equal to 1.5x ULN Alkaline phosphatase less than or equal to 1.5x ULN For females of reproductive potential, a negative serum or urine pregnancy test with a sensitivity of 25 mIU/mL within 72 hours, inclusive, prior to study entry All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) All participants of reproductive potential, who were participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception while receiving the study drugs and for 7 weeks after stopping the medications Ability and willingness of participant or legal representative to provide written informed consent and attend study visits as scheduled at a participating site Exclusion Criteria: A current or past history of progressive multifocal leukoencephalopathy Breastfeeding or pregnancy Use of strong inhibitors or inducers of CYP3A4 including a protease inhibitor, cobicistat or entry inhibitors as part of the current ART regimen or other concomitant therapy Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements Acute or serious illness or infection requiring systemic treatment and/or hospitalization within 60 days prior to entry Vaccinations (other than influenza) less than or equal to 45 days prior to the study entry visit. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy or investigational therapy less than or equal to 60 days prior to study entry Any current diagnosis or past history of a significant cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, neuropsychiatric, psychiatric, or other serious illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data or affect the participant's ability to participate in the study. Diagnoses that would lead to exclusion include, but were not limited to the following: CDC category C AIDS-indicator conditions NOTE A: Except HIV encephalopathy, HIV wasting, esophageal candidiasis, or pneumocystis pneumonia without dissemination. NOTE B: List available: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm Herpes zoster (dermatomal or non-dermatomal). NOTE C: A history of prior chickenpox was not exclusionary. Lymphoproliferative malignancy Chronic liver disease of any etiology and any degree of severity Chronic hepatitis, except for hepatitis C that has been cured (defined as a Sustained Virologic Response, which is an undetectable HCV-RNA at 12 weeks or more after completing treatment measured by a sensitive, qualitative, or quantitative HCV-RNA assay) Disseminated fungal infection of any type or duration that is not limited to cutaneous or mucocutaneous surfaces A medical disorder that predisposes to bleeding Change in the ART regimen within 12 weeks, inclusive, prior to study entry or intended modification of ART during the study. History of untreated latent tuberculosis infection (LTBI) diagnosed by tuberculin skin test or interferon gamma release assay. LTBI treatment would consist of 9 months of isoniazid or an equivalent therapy completed at least 4 weeks prior to study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vincent Marconi, MD
Organizational Affiliation
Emory University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jeffrey Lennox, MD
Organizational Affiliation
Emory University
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama CRS
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90035
Country
United States
Facility Name
UCSD Antiviral Research Center CRS
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Ucsf Hiv/Aids Crs
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Washington University Therapeutics (WT) CRS
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1010
Country
United States
Facility Name
Weill Cornell Chelsea CRS
City
New York
State/Province
New York
ZIP/Postal Code
10010
Country
United States
Facility Name
Weill Cornell Uptown CRS
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester Adult HIV Therapeutic Strategies Network CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Cincinnati Clinical Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Case Clinical Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Penn Therapeutics, CRS
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Vanderbilt Therapeutics (VT) CRS
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37204
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33693561
Citation
Marconi VC, Moser C, Gavegnano C, Deeks SG, Lederman MM, Overton ET, Tsibris A, Hunt PW, Kantor A, Sekaly RP, Tressler R, Flexner C, Hurwitz SJ, Moisi D, Clagett B, Hardin WR, Del Rio C, Schinazi RF, Lennox JJ. Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults With Human Immunodeficiency Virus. Clin Infect Dis. 2022 Jan 7;74(1):95-104. doi: 10.1093/cid/ciab212.
Results Reference
derived
Links:
URL
https://rsc.niaid.nih.gov/sites/default/files/daids-ae-grading-table-v2-nov2014.pdf
Description
DAIDS AE Grading Table, Version 2.0, November 2014
URL
https://rsc.niaid.nih.gov/sites/default/files/manual-exped-aes-v2_0.pdf
Description
Version 2.0 of the DAIDS EAE Manual

Learn more about this trial

Evaluating the Safety and Tolerability of Ruxolitinib in Antiretroviral-Treated HIV-Infected Adults

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