Back to resultsA Safety Study of Brentuximab Vedotin in Participants With HIV
Primary Purpose
Human Immunodeficiency Virus
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
brentuximab vedotin
Placebo
ART
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus focused on measuring HIV, Immunological Nonresponder, Seattle Genetics
Eligibility Criteria
Inclusion Criteria:
- HIV-1 seropositive with documentation of infection
Immunological nonresponder, defined as:
- Has been on ART with an HIV viral load <50 copies/mL for at least 24 months
- Has a CD4+ T-cell lymphocyte count between 51 to 200 cells/µL
- Life expectancy of >9 months.
- Participant is negative for hepatitis B, or if infected with hepatitis B, receiving anti-hepatitis B therapy
- Participants with a history of hepatitis C virus (HCV) are eligible if they have completed therapy for HCV and show sustained virologic remission (12 weeks or more)
Exclusion Criteria:
Any currently active AIDS-defining illness per Category C conditions according to the CDC Classification System for HIV Infection, with the following exceptions:
- Limited cutaneous Kaposi's sarcoma not currently requiring systemic therapy
- Wasting syndrome due to HIV or any other AIDS-defining illness for which no therapeutic treatment is required OR the required treatment is not included in the list of prohibited medications
- Acute liver disease or any other active infection secondary to HIV requiring acute therapy
- History of progressive multifocal leukoencephalopathy (PML)
- Prior clinical John Cunningham virus (JCV) infection, history of JCV identified in cerebrospinal fluid, or presence of JCV antibodies at screening
- Cirrhosis secondary to any cause
- Any immunomodulating therapy (excluding premedication steroid) within 4 weeks prior to the screening visit
- Prior malignancy within 2 years other than cutaneous basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, anal intraepithelial neoplasia, or cutaneous Kaposi's sarcoma
Sites / Locations
- University of California at San Francisco
- University of Illinois at Chicago
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Brentuximab vedotin + ART
Placebo + ART
Arm Description
Brentuximab vedotin given on Day 1 and Day 15. ART will be given throughout the study.
Placebo given on Day 1 and Day 15. ART will be given throughout the study.
Outcomes
Primary Outcome Measures
Number of participants with adverse events (AEs)
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment
Number of participants with laboratory abnormalities
Number of participants with dose-limiting toxicities (DLTs) by dose level
Secondary Outcome Measures
Area under the concentration-time curve (AUC)
Pharmacokinetic (PK) Parameter
Maximum concentration (Cmax)
PK Parameter
Time to maximum concentration (Tmax)
PK Parameter
Apparent terminal half-life (t1/2)
PK Parameter
Trough concentration (Ctrough)
PK Parameter
Incidence of antidrug antibodies (ADAs)
Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL
Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL, with a minimum increase of 50 cells/µL
Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL
The time from start of the first occurrence of CD4+ T-cell count increases to the level >200 cells/µL to the first occurrence of CD4+ T-cell count to the level <200 cells/µL
Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL with a minimum increase of 50 cells/µL
The time from start of the first occurrence of CD4+ T-cell count increases to the level >200 cells/µL to the first occurrence of CD4+ T-cell count to the level <200 cells/µL with a minimum increase of 50 cells/µL
Change from baseline in CD4+ T-cell lymphocyte counts
The change from baseline in CD4+ T-cell lymphocyte counts will be summarized based on observed values.
Change from baseline in CD4+ T cell percentage
The change from baseline in CD4+ T cell percentage will be summarized based on observed values.
Change from baseline in CD8+ T-cell lymphocyte counts
The change from baseline CD8+ T-cell lymphocyte counts will be summarized based on observed values.
Change from baseline in CD4:CD8 ratio
The change from baseline in CD4:CD8 ratio will be summarized.
Change from baseline in Treg and other T-cell subsets
Proportion of subjects with HIV viral load <50 copies/mL
The proportion of subjects with HIV viral load <50 copies/mL will be summarized.
Proportion of subjects with fatal or non-fatal acquired immunodeficiency syndrome (AIDS) related opportunistic disease or death from any cause
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05244473
Brief Title
A Safety Study of Brentuximab Vedotin in Participants With HIV
Official Title
A Phase 1, Single-blind, Dose-escalation Study to Assess the Safety and Tolerability of Brentuximab Vedotin (ADCETRIS®) in Subjects With Human Immunodeficiency Virus (HIV)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Study withdrawn due to low patient accrual.
Study Start Date
December 31, 2022 (Anticipated)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
May 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seagen Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will test brentuximab vedotin to see if it is safe for people with human immunodeficiency virus (HIV) who have low CD4+ and have received antiretroviral therapy (ART) treatment. It will also see if brentuximab vedotin raises CD4+ counts. It will study the side effects of this drug as well. A side effect is anything a drug does to the body besides treating the disease.
In this study participants will be assigned randomly to a group. Participants will get either brentuximab vedotin or placebo. A placebo looks like the drug but does not contain any medicine in it. All participants will keep getting ART during the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus
Keywords
HIV, Immunological Nonresponder, Seattle Genetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Brentuximab vedotin + ART
Arm Type
Experimental
Arm Description
Brentuximab vedotin given on Day 1 and Day 15. ART will be given throughout the study.
Arm Title
Placebo + ART
Arm Type
Placebo Comparator
Arm Description
Placebo given on Day 1 and Day 15. ART will be given throughout the study.
Intervention Type
Drug
Intervention Name(s)
brentuximab vedotin
Other Intervention Name(s)
ADCETRIS
Intervention Description
Given into the vein (IV; intravenously)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Given by IV
Intervention Type
Drug
Intervention Name(s)
ART
Intervention Description
Daily use of a combination of HIV medicines
Primary Outcome Measure Information:
Title
Number of participants with adverse events (AEs)
Description
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment
Time Frame
Through 30 days after last study treatment
Title
Number of participants with laboratory abnormalities
Time Frame
Approximately 1 year
Title
Number of participants with dose-limiting toxicities (DLTs) by dose level
Time Frame
Up to 30 days
Secondary Outcome Measure Information:
Title
Area under the concentration-time curve (AUC)
Description
Pharmacokinetic (PK) Parameter
Time Frame
Approximately 4 months
Title
Maximum concentration (Cmax)
Description
PK Parameter
Time Frame
Approximately 4 months
Title
Time to maximum concentration (Tmax)
Description
PK Parameter
Time Frame
Approximately 4 months
Title
Apparent terminal half-life (t1/2)
Description
PK Parameter
Time Frame
Approximately 4 months
Title
Trough concentration (Ctrough)
Description
PK Parameter
Time Frame
Approximately 4 months
Title
Incidence of antidrug antibodies (ADAs)
Time Frame
Approximately 4 months
Title
Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL
Time Frame
Approximately 1 year
Title
Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL, with a minimum increase of 50 cells/µL
Time Frame
Approximately 1 year
Title
Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL
Description
The time from start of the first occurrence of CD4+ T-cell count increases to the level >200 cells/µL to the first occurrence of CD4+ T-cell count to the level <200 cells/µL
Time Frame
Approximately 1 year
Title
Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL with a minimum increase of 50 cells/µL
Description
The time from start of the first occurrence of CD4+ T-cell count increases to the level >200 cells/µL to the first occurrence of CD4+ T-cell count to the level <200 cells/µL with a minimum increase of 50 cells/µL
Time Frame
Approximately 1 year
Title
Change from baseline in CD4+ T-cell lymphocyte counts
Description
The change from baseline in CD4+ T-cell lymphocyte counts will be summarized based on observed values.
Time Frame
Approximately 1 year
Title
Change from baseline in CD4+ T cell percentage
Description
The change from baseline in CD4+ T cell percentage will be summarized based on observed values.
Time Frame
Approximately 1 year
Title
Change from baseline in CD8+ T-cell lymphocyte counts
Description
The change from baseline CD8+ T-cell lymphocyte counts will be summarized based on observed values.
Time Frame
Approximately 1 year
Title
Change from baseline in CD4:CD8 ratio
Description
The change from baseline in CD4:CD8 ratio will be summarized.
Time Frame
Approximately 1 year
Title
Change from baseline in Treg and other T-cell subsets
Time Frame
Approximately 6 months
Title
Proportion of subjects with HIV viral load <50 copies/mL
Description
The proportion of subjects with HIV viral load <50 copies/mL will be summarized.
Time Frame
Approximately 1 year
Title
Proportion of subjects with fatal or non-fatal acquired immunodeficiency syndrome (AIDS) related opportunistic disease or death from any cause
Time Frame
Approximately 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HIV-1 seropositive with documentation of infection
Immunological nonresponder, defined as:
Has been on ART with an HIV viral load <50 copies/mL for at least 24 months
Has a CD4+ T-cell lymphocyte count between 51 to 200 cells/µL
Life expectancy of >9 months.
Participant is negative for hepatitis B, or if infected with hepatitis B, receiving anti-hepatitis B therapy
Participants with a history of hepatitis C virus (HCV) are eligible if they have completed therapy for HCV and show sustained virologic remission (12 weeks or more)
Exclusion Criteria:
Any currently active AIDS-defining illness per Category C conditions according to the CDC Classification System for HIV Infection, with the following exceptions:
Limited cutaneous Kaposi's sarcoma not currently requiring systemic therapy
Wasting syndrome due to HIV or any other AIDS-defining illness for which no therapeutic treatment is required OR the required treatment is not included in the list of prohibited medications
Acute liver disease or any other active infection secondary to HIV requiring acute therapy
History of progressive multifocal leukoencephalopathy (PML)
Prior clinical John Cunningham virus (JCV) infection, history of JCV identified in cerebrospinal fluid, or presence of JCV antibodies at screening
Cirrhosis secondary to any cause
Any immunomodulating therapy (excluding premedication steroid) within 4 weeks prior to the screening visit
Prior malignancy within 2 years other than cutaneous basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, anal intraepithelial neoplasia, or cutaneous Kaposi's sarcoma
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrei Shustov, MD
Organizational Affiliation
Seagen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of California at San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Safety Study of Brentuximab Vedotin in Participants With HIV
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