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Elotuzumab in Immunoglobulin G4-Related Disease (IgG4-RD)

Primary Purpose

IgG4 Related Disease, IgG4-RD

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
elotuzumab
placebo for elotuzumab
methylprednisolone
diphenhydramine
acetaminophen
famotidine
prednisone
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 IgG4 Related Disease focused on measuring immune-mediated fibroinflammatory disease, prospective trial, safety and efficacy, IgG4-RD Responder Index (IgG4-RD RI)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

  1. Participant must be able to understand and provide informed consent and be willing to comply with study procedures and follow up;
  2. Meet the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria for IgG4-Related Disease (IgG4-RD);
  3. Have active disease based at screening on an IgG4-RD Responder Index (RI) ≥4, with disease manifestations in at least two organ systems;
  4. May have newly-diagnosed or relapsing disease at screening

    --Relapsing disease is defined as IgG4-RD that has previously been in remission but is now active again;

  5. May be on treatment or off treatment for IgG4-RD at the time of screening

    --If on treatment, must be willing to discontinue those other treatments before the Baseline (Day 0) visit;

  6. No history of severe allergic reactions to monoclonal antibodies;
  7. Female participants of childbearing potential must have a negative pregnancy test upon study entry;
  8. Female participants of childbearing potential and male participants with a partner of childbearing potential must agree to use Food and Drug Administration (FDA) approved methods of birth control for the entire duration of the study; and,
  9. Immunization with one of the FDA authorized or licensed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines is required for study entry

    • Vaccination series must have been completed at least 2 weeks prior to start of study therapy
    • Participants with Coronavirus Disease 2019 (COVID-19) infections within the preceding three months must have 2 consecutive negative nasal swab Polymerase Chain Reaction (PCR) tests performed at least 24 hours apart.

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for enrollment as study participants:

  1. Treatment with more than 40 mg/day of prednisone within 28 days of the Baseline (Day 0) visit;
  2. Presence of a condition other than IgG4-RD that (e.g., asthma) is likely to require systemic glucocorticoids (GC) for disease control during the period of the trial;
  3. Malignancy within 5 years (except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin);
  4. The following lab values as indicators of hepatic dysfunction:

    • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater (>) than three times the upper limit of normal (ULN)
    • Total bilirubin >two times the ULN unless caused by Gilbert's disease

      ---Gilbert's disease with total bilirubin > three times ULN

    • Serum albumin <2.5 mg/dL;
  5. Evidence of another uncontrolled condition which, in the judgment of the investigator, could interfere with participation in the trial according to the protocol;
  6. Active infection requiring hospitalization or treatment with systemic antimicrobial agents within the 30 days prior to randomization;
  7. Prior use of rituximab or other B cell depleting agents within 9 months of enrollment, unless B cells have been demonstrated to have repopulated;
  8. Use of any investigational agent or biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs) within 5 half-lives of the agent (or 6 months if the half- life is unknown) prior to enrollment;
  9. Any of the following laboratory tests at the Screening Visit:

    • White blood cell count (WBC) <3.0 x 10^3/microliter (µL)
    • Absolute neutrophil count (ANC) <1.5 x 10^3/µL
    • Hemoglobin <10 g/dL
    • Platelet count <75 x 10^9/L
    • Estimated glomerular filtration rate (eGFR) ≤45 ml/minute/1.73m^2;
  10. The use of supplemental oxygen at baseline (Day 0);
  11. Positive Quantiferon gold assay

    • Indeterminate Quantiferon gold assays must be repeated (with same or other interferon gamma release assay (IGRA) per local policy) and shown to be negative

      ---Alternatively, if the Quantiferon gold assay remains indeterminant, a participant must have a negative purified protein derivative (PPD)

    • If the participant has had the Bacillus Calmette-Guérin (BCG) vaccine or has some other condition complicating the interpretation of tuberculosis (TB) testing, consultation with infectious disease specialist must be obtained before receipt of the first investigational infusion ----Note: Participants diagnosed with latent TB are eligible but must have received appropriate prophylaxis for 30 days before their first investigational infusion;
  12. Medical history or serologic evidence at Screening of chronic infections including:

    • Human immunodeficiency virus (HIV) infection
    • Hepatitis B as indicated by surface antigen or hepatitis B core antibody positivity
    • Hepatitis C as indicated by anti-hepatitis C antibody positivity ---If a participant is Hepatitis C antibody positive, they will be eligible to participate in the study if he/she is negative for viral load at Screening;
  13. Live vaccines within 8 weeks of initiating study therapy;
  14. Participant is pregnant or breastfeeding, or planning a pregnancy while enrolled in the study;
  15. Substance use disorder, including the recurrent use of alcohol and/or drugs within the past year associated with clinically significant impairment associated with failure to meet major responsibilities at work, school, or home;
  16. IgG4-RD that is dominated primarily by advanced fibrotic lesions (°)

    --Specifically, participants whose disease manifestations consist only of:

    • retroperitoneal fibrosis,
    • fibrosing mediastinitis,
    • sclerosing mesenteritis, or
    • Riedel's thyroiditis

    (°) Participants with these (Exclusion item 16) disease manifestations can be included, however, only if they have disease in 2 organ systems that is not of an advanced fibrotic nature and otherwise meet the Inclusion and Exclusion Criteria; or,

  17. Co-enrollment: While participating in AIG01, participants may not be in another interventional trial, but may be in observational registries or cohorts as long as the total combined volume of blood to be drawn does not exceed the National Institutes of Health (NIH) limit of and objectives do not confound the current study.

Sites / Locations

  • Emory HealthcareRecruiting
  • Massachusetts General HospitalRecruiting
  • Mayo Clinic: Pulmonary and Critical Care MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Cohort 1a: Elotuzumab-One-Month Regimen (Open-Label) + Pred Taper

Cohort 1b: Elotuzumab-Twelve-Month Regimen (Open-Label) + Pred Taper

Cohort 2: Arm A- Elotuzumab (Randomized) + Pred Taper

Cohort 2: Arm B-Placebo (Randomized) + Pred Taper

Arm Description

Per protocol: Six participants will receive elotuzumab on days 0,7, 14, 21, and the prescribed 10-week prednisone taper. Elotuzumab: 10 mg/kg administered once weekly, intravenously for 4 doses, per protocol. Prednisone taper (Pred Taper): Prescribed 10-week dosing taper beginning on Day 0 (baseline) that is taken orally (by mouth) daily, per protocol. Dosage in milligrams (mgs).

Per protocol: Six participants will receive elotuzumab over a 48 week period, dose of 10mg/kg IV x 1, at baseline, then at weeks 8, 16, 24, 32 and 40 (for a total of 6 doses), with the prescribed 10-week prednisone taper. Elotuzumab: 10 mg/kg administered as referenced above, intravenously, per protocol. Prednisone taper (Pred Taper): Prescribed 10-week dosing taper beginning on Day 0 (baseline) that is taken orally (by mouth) daily, per protocol. Dosage in milligrams (mgs).

Safety and efficacy analyses from Cohort 1a and Cohort 1b will occur prior to initiating Cohort 2 (Randomized). Assuming no safety signal for Cohort 1, forty-two participants will receive elotuzumab per the regimen prescribed above in Part 1B, with the prescribed 10-week prednisone taper. Elotuzumab: 10 mg/kg administered as referenced above, intravenously, per protocol. Prednisone taper (Pred Taper): Prescribed 10-week dosing taper beginning on Day 0 that is taken daily by mouth, per protocol. Dosage in milligrams (mgs).

Safety and efficacy analyses from Cohort 1a and Cohort 1b will occur prior to initiating Cohort 2 (Randomized). Twenty-one participants will receive placebo for elotuzumab on day 0, then weeks 8, 16, 24, 32 and 40, and the prescribed 10-week prednisone taper. Placebo for elotuzumab: Administered on same schedule as elotuzumab described in Cohort 2 Arm A: intravenously, per protocol. Prednisone taper (Pred Taper): Prescribed 10-week dosing taper beginning on Day 0 taken daily by mouth, per protocol. Dosage in milligrams (mgs).

Outcomes

Primary Outcome Measures

Proportion of Participants in Cohort 1a Who Experience at Least One Grade 3 or Higher Adverse Event
Safety measure. Evaluation of the severity of adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Proportion of Participants in Cohort 1b Who Experience at Least One Grade 3 or Higher Adverse Event
Safety measure. Evaluation of the severity of adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Participants in Cohort 2: Percent Change in Immunoglobulin G4-Related Disease Responder Index (IgG4-RD RI) Score
Efficacy measure. The IgG4-RD RI is used to assess disease response to treatments in IgG4-RD clinical trials.

Secondary Outcome Measures

Proportion of Participants by Cohort Group who Experience at Least One Grade 2 or Higher Adverse Event
Safety measure. Evaluation of the severity of adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Proportion of Participants by Cohort Group with a Grade 3 or Higher Infection
Safety measure. Evaluation of the severity of infectious disease(s) adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Proportion of Participants by Cohort Group who Experience a Malignancy
Safety measure. Evaluation of the severity of infectious disease(s) adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Proportion of Participants by Cohort Group who Experience a Hepatotoxicity
Safety measure. Defined as an increase in the serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) to elevations three times the upper limit of normal (ULN).
Proportion of Participants by Cohort Group who Experience a Serious Adverse Event
Safety measure defined as an adverse event or suspected adverse reaction that, in the view of either the investigator or sponsor results in any of the following outcomes (21 CFR 312.32(a)): Death A life-threatening event Inpatient hospitalization or prolongation of existing hospitalization Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions Congenital anomaly or birth defect Important medical events that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above
Proportion of Participants by Cohort Group who Experience Infusion Reactions
Safety measure defined as any adverse reaction within 24 hours of infusion which are Grade 2 or higher events and at least possibly related to study drug.
Proportion of Participants in Cohort 2 who Experience at Least One Grade 3 or Higher Adverse Event
Safety measure. Evaluation of the severity of adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Proportion of Participants in Cohort 2 in Complete Remission at Week 48
Efficacy measure, defined as: An IgG4-RD Responder Index (IgG4-RD RI) score of 0, A glucocorticoid dose of 0 mg/day, and No disease flare since beginning treatment.
Proportion of Participants by Cohort Group who Achieve ≥50 Percent (%) Improvement in IgG4-RD Responder Index (IgG4-RD RI) Score at Week 48
Efficacy measure. The IgG4-RD RI is used to assess disease response to treatments in IgG4-RD clinical trials. The IgG4-RD Responder Index Total Activity Score ranges from 0 to a maximum of 162. Higher scores represent greater (i.e. worse) disease activity.
Proportion of Participants by Cohort Group who Achieve ≥75 Percent (%) Improvement in IgG4-RD Responder Index (IgG4-RD RI) Score at Week 48
Efficacy measure. The IgG4-RD RI is used to assess disease response to treatments in IgG4-RD clinical trials. The IgG4-RD Responder Index Total Activity Score ranges from 0 to a maximum of 162. Higher scores represent greater (i.e. worse) disease activity.
Number of Immunoglobulin G4-Related Disease (IgG4-RD) Flares by Cohort Group by Week 48
Efficacy measure, defined as a recurrence of disease activity such that additional immunosuppressive therapy beyond the trial protocol is indicated.
Change from Baseline in Physician Global Assessment (PhGA)-By Cohort Group
Efficacy measure.
Change from Baseline in Patient Global Assessment (PGA)-By Cohort Group
Efficacy measure.
Proportion of Participants by Cohort Group with Disease-Related Damage at Week 24
Efficacy measure. Disease-related damage, as measured by the damage section of the IgG4-RD Responder Index (IgG4-RD RI). The IgG4-RD RI is used to assess disease response to treatments in IgG4-RD clinical trials.

Full Information

First Posted
June 4, 2021
Last Updated
May 26, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Autoimmunity Centers of Excellence, Bristol-Myers Squibb, Rho Federal Systems Division, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04918147
Brief Title
Elotuzumab in Immunoglobulin G4-Related Disease (IgG4-RD)
Official Title
Elotuzumab in Immunoglobulin G4-Related Disease (IgG4-RD)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 13, 2021 (Actual)
Primary Completion Date
November 30, 2026 (Anticipated)
Study Completion Date
November 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Autoimmunity Centers of Excellence, Bristol-Myers Squibb, Rho Federal Systems Division, 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 is a two-part multi-center clinical trial in participants with active IgG4-RD. Part 1 (Cohort 1a and Cohort 1B) is an open-label, dose escalation phase to determine the safety of elotuzumab for investigation in IgG4-RD. Part 2 (Cohort 2) is a randomized, placebo-controlled, double-blinded (masked) trial phase to compare the effects of elotuzumab and prednisone to elotuzumab placebo and prednisone in participants with IgG4 RD. Approximately 75 participants with active IgG4-RD will be enrolled in the overall program, 12 in Part 1 and 63 in Part 2. Randomization in Part 2: 2 to 1, with approximately forty-two participants randomized to elotuzumab plus prednisone taper, and twenty-one participants randomized to placebo for elotuzumab plus prednisone taper. The total duration of participation for each participant in this trial will be 48 weeks (11 months).
Detailed Description
Immunoglobulin G4-Related Disease (IgG4-RD) is a chronic fibro-inflammatory condition that can affect virtually every organ system, including the pancreas, biliary tract, salivary and lacrimal glands, orbits, lungs, kidneys, meninges, pituitary gland, prostate and thyroid. It may also involve the retroperitoneum. This multi-organ immune-mediated condition, once regarded as a group of isolated, single-organ diseases, is now recognized to be an overarching, single-disease entity linked by common histopathological and immunohistochemical features. IgG4-RD tends to afflict middle-aged to elderly individuals. Although IgG4-RD can affect a single organ at presentation, it is not uncommon for participants to present with or develop multi-organ disease. As the disease progresses, additional organs develop lesions and the cellular inflammation characterizing early disease moves toward a more fibrotic stage, causing major tissue damage, dysfunction and ultimately organ failure. It is unclear whether IgG4 itself is involved in the pathogenesis of the disease. The goals of IgG4-RD treatment are to reduce inflammation and organ swelling and to prevent or reverse tissue fibrosis. No approved therapy exists for IgG4-RD. This study will enroll adult participants who meet the 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria for IgG4-RD, and who have active IgG4-RD with disease manifestations in at least two organ systems. Primary study objectives: To determine the safety and tolerability of the addition of elotuzumab to prednisone in participants with IgG4-RD, and To compare the effect of the addition of elotuzumab versus placebo to prednisone on the IgG4-RD Responder Index (IgG4-RD RI), a measure of IgG4-RD disease activity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IgG4 Related Disease, IgG4-RD
Keywords
immune-mediated fibroinflammatory disease, prospective trial, safety and efficacy, IgG4-RD Responder Index (IgG4-RD RI)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1a: Elotuzumab-One-Month Regimen (Open-Label) + Pred Taper
Arm Type
Experimental
Arm Description
Per protocol: Six participants will receive elotuzumab on days 0,7, 14, 21, and the prescribed 10-week prednisone taper. Elotuzumab: 10 mg/kg administered once weekly, intravenously for 4 doses, per protocol. Prednisone taper (Pred Taper): Prescribed 10-week dosing taper beginning on Day 0 (baseline) that is taken orally (by mouth) daily, per protocol. Dosage in milligrams (mgs).
Arm Title
Cohort 1b: Elotuzumab-Twelve-Month Regimen (Open-Label) + Pred Taper
Arm Type
Experimental
Arm Description
Per protocol: Six participants will receive elotuzumab over a 48 week period, dose of 10mg/kg IV x 1, at baseline, then at weeks 8, 16, 24, 32 and 40 (for a total of 6 doses), with the prescribed 10-week prednisone taper. Elotuzumab: 10 mg/kg administered as referenced above, intravenously, per protocol. Prednisone taper (Pred Taper): Prescribed 10-week dosing taper beginning on Day 0 (baseline) that is taken orally (by mouth) daily, per protocol. Dosage in milligrams (mgs).
Arm Title
Cohort 2: Arm A- Elotuzumab (Randomized) + Pred Taper
Arm Type
Experimental
Arm Description
Safety and efficacy analyses from Cohort 1a and Cohort 1b will occur prior to initiating Cohort 2 (Randomized). Assuming no safety signal for Cohort 1, forty-two participants will receive elotuzumab per the regimen prescribed above in Part 1B, with the prescribed 10-week prednisone taper. Elotuzumab: 10 mg/kg administered as referenced above, intravenously, per protocol. Prednisone taper (Pred Taper): Prescribed 10-week dosing taper beginning on Day 0 that is taken daily by mouth, per protocol. Dosage in milligrams (mgs).
Arm Title
Cohort 2: Arm B-Placebo (Randomized) + Pred Taper
Arm Type
Placebo Comparator
Arm Description
Safety and efficacy analyses from Cohort 1a and Cohort 1b will occur prior to initiating Cohort 2 (Randomized). Twenty-one participants will receive placebo for elotuzumab on day 0, then weeks 8, 16, 24, 32 and 40, and the prescribed 10-week prednisone taper. Placebo for elotuzumab: Administered on same schedule as elotuzumab described in Cohort 2 Arm A: intravenously, per protocol. Prednisone taper (Pred Taper): Prescribed 10-week dosing taper beginning on Day 0 taken daily by mouth, per protocol. Dosage in milligrams (mgs).
Intervention Type
Drug
Intervention Name(s)
elotuzumab
Other Intervention Name(s)
BMS-901608, Empliciti®
Intervention Description
Elotuzumab is a humanized recombinant monoclonal antibody (mAb) targeted against SLAMF7, a cell surface glycoprotein.
Intervention Type
Drug
Intervention Name(s)
placebo for elotuzumab
Other Intervention Name(s)
normal saline
Intervention Description
The placebo for elotuzumab is 0.9% sterile normal saline for injection.
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Other Intervention Name(s)
Solu-Medrol®
Intervention Description
Premedication administered intravenously, 45 to 90 minutes prior to each elotuzumab/placebo infusion, per protocol. Dosage in milligrams (mg).
Intervention Type
Drug
Intervention Name(s)
diphenhydramine
Other Intervention Name(s)
Benadryl®
Intervention Description
Premedication administered orally or intravenously, 45 to 90 minutes prior to each elotuzumab/placebo infusion, per protocol. Dosage in milligrams (mg).
Intervention Type
Drug
Intervention Name(s)
acetaminophen
Other Intervention Name(s)
Tylenol®
Intervention Description
Premedication administered orally, 45 to 90 minutes prior to each elotuzumab/placebo infusion, per protocol. Dosage in milligrams (mg).
Intervention Type
Drug
Intervention Name(s)
famotidine
Other Intervention Name(s)
H2 blocker
Intervention Description
Premedication administered orally or intravenously, 45 to 90 minutes prior to each elotuzumab/placebo infusion, per protocol. Dosage in milligrams (mg).
Intervention Type
Drug
Intervention Name(s)
prednisone
Other Intervention Name(s)
corticosteroid
Intervention Description
Prescribed dosing with prednisone begins on the day of the first elotuzumab/placebo infusion, administered orally. The ten-week dosing taper proceeds, per protocol. Dosage in milligrams (mg).
Primary Outcome Measure Information:
Title
Proportion of Participants in Cohort 1a Who Experience at Least One Grade 3 or Higher Adverse Event
Description
Safety measure. Evaluation of the severity of adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time Frame
Up to Week 24 post treatment initiation
Title
Proportion of Participants in Cohort 1b Who Experience at Least One Grade 3 or Higher Adverse Event
Description
Safety measure. Evaluation of the severity of adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time Frame
Up to Week 48 post treatment initiation
Title
Participants in Cohort 2: Percent Change in Immunoglobulin G4-Related Disease Responder Index (IgG4-RD RI) Score
Description
Efficacy measure. The IgG4-RD RI is used to assess disease response to treatments in IgG4-RD clinical trials.
Time Frame
Baseline (Day 0, prior to treatment initiation), Week 48
Secondary Outcome Measure Information:
Title
Proportion of Participants by Cohort Group who Experience at Least One Grade 2 or Higher Adverse Event
Description
Safety measure. Evaluation of the severity of adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time Frame
Up to Week 48 post treatment initiation
Title
Proportion of Participants by Cohort Group with a Grade 3 or Higher Infection
Description
Safety measure. Evaluation of the severity of infectious disease(s) adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time Frame
Up to Week 48 post treatment initiation
Title
Proportion of Participants by Cohort Group who Experience a Malignancy
Description
Safety measure. Evaluation of the severity of infectious disease(s) adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time Frame
Up to Week 48 post treatment initiation
Title
Proportion of Participants by Cohort Group who Experience a Hepatotoxicity
Description
Safety measure. Defined as an increase in the serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) to elevations three times the upper limit of normal (ULN).
Time Frame
Up to Week 48 post treatment initiation
Title
Proportion of Participants by Cohort Group who Experience a Serious Adverse Event
Description
Safety measure defined as an adverse event or suspected adverse reaction that, in the view of either the investigator or sponsor results in any of the following outcomes (21 CFR 312.32(a)): Death A life-threatening event Inpatient hospitalization or prolongation of existing hospitalization Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions Congenital anomaly or birth defect Important medical events that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above
Time Frame
Up to Week 48 post treatment initiation
Title
Proportion of Participants by Cohort Group who Experience Infusion Reactions
Description
Safety measure defined as any adverse reaction within 24 hours of infusion which are Grade 2 or higher events and at least possibly related to study drug.
Time Frame
Up to 24 hours post treatment infusion
Title
Proportion of Participants in Cohort 2 who Experience at Least One Grade 3 or Higher Adverse Event
Description
Safety measure. Evaluation of the severity of adverse events. Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time Frame
Up to Week 48 post treatment initiation
Title
Proportion of Participants in Cohort 2 in Complete Remission at Week 48
Description
Efficacy measure, defined as: An IgG4-RD Responder Index (IgG4-RD RI) score of 0, A glucocorticoid dose of 0 mg/day, and No disease flare since beginning treatment.
Time Frame
Week 48 post treatment initiation
Title
Proportion of Participants by Cohort Group who Achieve ≥50 Percent (%) Improvement in IgG4-RD Responder Index (IgG4-RD RI) Score at Week 48
Description
Efficacy measure. The IgG4-RD RI is used to assess disease response to treatments in IgG4-RD clinical trials. The IgG4-RD Responder Index Total Activity Score ranges from 0 to a maximum of 162. Higher scores represent greater (i.e. worse) disease activity.
Time Frame
Week 48 post treatment initiation
Title
Proportion of Participants by Cohort Group who Achieve ≥75 Percent (%) Improvement in IgG4-RD Responder Index (IgG4-RD RI) Score at Week 48
Description
Efficacy measure. The IgG4-RD RI is used to assess disease response to treatments in IgG4-RD clinical trials. The IgG4-RD Responder Index Total Activity Score ranges from 0 to a maximum of 162. Higher scores represent greater (i.e. worse) disease activity.
Time Frame
Week 48 post treatment initiation
Title
Number of Immunoglobulin G4-Related Disease (IgG4-RD) Flares by Cohort Group by Week 48
Description
Efficacy measure, defined as a recurrence of disease activity such that additional immunosuppressive therapy beyond the trial protocol is indicated.
Time Frame
Up to Week 48 post treatment initiation
Title
Change from Baseline in Physician Global Assessment (PhGA)-By Cohort Group
Description
Efficacy measure.
Time Frame
Baseline through Week 48
Title
Change from Baseline in Patient Global Assessment (PGA)-By Cohort Group
Description
Efficacy measure.
Time Frame
Baseline through Week 48
Title
Proportion of Participants by Cohort Group with Disease-Related Damage at Week 24
Description
Efficacy measure. Disease-related damage, as measured by the damage section of the IgG4-RD Responder Index (IgG4-RD RI). The IgG4-RD RI is used to assess disease response to treatments in IgG4-RD clinical trials.
Time Frame
Week 48 post treatment initiation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Individuals who meet all of the following criteria are eligible for enrollment as study participants: Participant must be able to understand and provide informed consent and be willing to comply with study procedures and follow up. Are at least 18 years of age and not older than 70 years of age at screening. Meet the ACR/EULAR Classification Criteria for IgG4-RD [30, 31]. Have active disease based at screening on an IgG4-RD RI ≥4, with disease manifestations in at least two organ systems. May have newly-diagnosed or relapsing disease at screening. Relapsing disease is defined as IgG4-RD that has previously been in remission but is now active again. May be on treatment or off treatment for IgG4-RD at the time of screening. If on treatment, must be willing to discontinue those other treatments before the baseline visit. No history of severe allergic reactions to monoclonal antibodies. Female participants of childbearing potential must have a negative pregnancy test upon study entry. Female participants of childbearing potential and male participants with a partner of childbearing potential must agree to consistently and correctly use FDA approved highly effective methods of birth control for the entire duration of the study and 6 months after last elotuzumab infusion. Immunization with one of the FDA authorized or licensed SARS-CoV-2 vaccines as per CDC recommendations at the time of informed consent is required for study entry. Vaccinations must have been completed at least 2 weeks prior to start of study therapy. Exclusion Criteria: Individuals who meet any of these criteria are not eligible for enrollment as study participants: Presence of a condition other than IgG4-RD that (e.g., asthma) is likely to require systemic Glucocorticoids (GC) for disease control during the period of the trial. Malignancy within 5 years (except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin.) The following lab values as indicators of hepatic dysfunction: Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three times the upper limit of normal (ULN) Total bilirubin > two times the ULN unless caused by Gilbert's disease. Gilbert's disease with total bilirubin > three times ULN. Serum albumin < 2.5 gm/dL. Evidence of another uncontrolled condition which, in the judgment of the investigator, could interfere with participation in the trial according to the protocol. Active infection requiring hospitalization or treatment with systemic antimicrobial agents within the 30 days prior to treatment allocation/randomization. Prior use of rituximab or other B cell depleting agents within 9 months of enrollment unless B cells have been demonstrated to have repopulated. Use of any investigational agent or biologic and non-biologic DMARDs within 5 half-lives of the agent (or 6 months if the half-life is unknown) prior to enrollment. Any of the following laboratory tests at the Screening Visit: White blood cell count (WBC) < 3.0 x 103/µL. Absolute neutrophil count (ANC) < 1.5 x 103/µL. Hemoglobin < 10 g/dL. Platelet count < 75 x 109/L. Estimated glomerular filtration rate (eGFR) ≤ 45 ml/minute/1.73 m2. The use of supplemental oxygen at baseline. At or within 90 days of screening: Positive Interferon-Gamma Release Assay (IGRA). Indeterminate IGRAs must be repeated (with same or other IGRA per local policy) and shown to be negative. Alternatively, if the assay remains indeterminant, a participant must have a negative PPD. Finally, if the participant has had the Bacille Calmette-Guerin (BCG) vaccine or has some other condition complicating the interpretation of TB testing, consultation with infectious disease specialist must be obtained before receipt of the first investigational infusion. a. Participants diagnosed with latent TB are eligible but must have received appropriate prophylaxis for 30 days before their first investigational infusion. Medical history or serologic evidence at Screening of chronic infections including: Human immunodeficiency virus infection. Hepatitis B as indicated by surface antigen or hepatitis B core antibody positivity Hepatitis C as indicated by anti-hepatitis C antibody positivity; if a participant is Hepatitis C antibody positive, they will be eligible to participate in the study if he/she is negative for viral load at Screening. Live vaccines within 8 weeks of initiating study therapy. Participant is pregnant or breastfeeding, or planning a pregnancy while enrolled in the study. Substance use disorder, including the recurrent use of alcohol and/or drugs within the past year associated with clinically significant impairment associated with failure to meet major responsibilities at work, school, or home. IgG4-RD that is dominated primarily by advanced fibrotic lesions. Specifically, participants whose disease manifestations consist only of retroperitoneal fibrosis, fibrosing mediatinitis, sclerosing mesenteritis, or Riedel's thyroiditis. Participants with these disease manifestations can be included, however, only if they have disease in 2 organ systems that is not of an advanced fibrotic nature and otherwise meet the Inclusion and Exclusion Criteria. Evidence a SARS-CoV-2 (COVID-19) infection started within the 30 days prior to treatment allocation/randomization. Participants diagnosed with SARS-CoV-2 (COVID-19) infection more than 30 days prior to treatment allocation/randomization must have symptoms resolved and be deemed fit to participate in the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John H. Stone, MD, MPH
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Emory Healthcare
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Varghese
Phone
404-727-2886
Email
john.varghese@emory.edu
First Name & Middle Initial & Last Name & Degree
Arezou Khosroshahi, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana D. Fernandes
Phone
617-643-2140
Email
Adfernandes@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
John H. Stone, MD, MPH
Facility Name
Mayo Clinic: Pulmonary and Critical Care Medicine
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adriana Delgado
Phone
507-422-5001
Email
Delgado.adriana@mayo.edu
First Name & Middle Initial & Last Name & Degree
Shounak Majumder, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
IPD Sharing Time Frame
On average, within 24 months after database lock for the trial.
IPD Sharing Access Criteria
Open access.
IPD Sharing URL
https://www.immport.org/home
Citations:
PubMed Identifier
31796497
Citation
Wallace ZS, Naden RP, Chari S, Choi HK, Della-Torre E, Dicaire JF, Hart PA, Inoue D, Kawano M, Khosroshahi A, Lanzillotta M, Okazaki K, Perugino CA, Sharma A, Saeki T, Schleinitz N, Takahashi N, Umehara H, Zen Y, Stone JH; Members of the ACR/EULAR IgG4-RD Classification Criteria Working Group. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020 Jan;79(1):77-87. doi: 10.1136/annrheumdis-2019-216561. Epub 2019 Dec 3.
Results Reference
background
PubMed Identifier
25809420
Citation
Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, Chari ST, Della-Torre E, Frulloni L, Goto H, Hart PA, Kamisawa T, Kawa S, Kawano M, Kim MH, Kodama Y, Kubota K, Lerch MM, Lohr M, Masaki Y, Matsui S, Mimori T, Nakamura S, Nakazawa T, Ohara H, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Shimatsu A, Shimosegawa T, Takahashi H, Takahira M, Tanaka A, Topazian M, Umehara H, Webster GJ, Witzig TE, Yamamoto M, Zhang W, Chiba T, Stone JH; Second International Symposium on IgG4-Related Disease. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015 Jul;67(7):1688-99. doi: 10.1002/art.39132. No abstract available.
Results Reference
background
Links:
URL
https://www.autoimmunitycenters.org/
Description
Autoimmunity Centers of Excellence (ACE)
URL
https://www.niaid.nih.gov/about/dait
Description
Division of Allergy, Immunology, and Transplantation (DAIT)
URL
https://www.niaid.nih.gov/
Description
National Institute of Allergy and Infectious Diseases (NIAID)

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Elotuzumab in Immunoglobulin G4-Related Disease (IgG4-RD)

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