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

NCT04918147 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: DAIT AIG01UM1AI144298NIAID CRMS ID#: 38708
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

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).

Conditions

IgG4 Related Disease; IgG4-RD

Keywords

immune-mediated fibroinflammatory disease; prospective trial; safety and efficacy; IgG4-RD Responder Index (IgG4-RD RI)

Outcome Measures

Primary Outcomes (1)

• The Percent of Participants in Each Cohort Who Experience at Least One Grade 3 or Higher Adverse Event (AE).

  The severity of AEs were classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0

  Up to Week 48 post treatment initiation

Secondary Outcomes (11)

• The Percent of Participants Who Experience at Least One Grade 2 or Higher Adverse Event (AE).

  Up to Week 48 post treatment initiation

• The Percent of Participants With a Grade 3 or Higher Infection

  Up to Week 48 post treatment initiation

• The Percent of Participants Who Experience a Malignancy.

  Up to Week 48 post treatment initiation

• The Percent of Participants Who Experience a Hepatotoxicity

  Up to Week 48 post treatment initiation

• The Percent of Participants Who Experience a Serious Adverse Event

  Up to Week 48 post treatment initiation

Study Arms (4)

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

EXPERIMENTAL

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).

Drug: elotuzumab; Drug: methylprednisolone; Drug: diphenhydramine; Drug: acetaminophen; Drug: famotidine; Drug: prednisone

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

EXPERIMENTAL

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).

Drug: elotuzumab; Drug: methylprednisolone; Drug: diphenhydramine; Drug: acetaminophen; Drug: famotidine; Drug: prednisone

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

EXPERIMENTAL

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).

Drug: elotuzumab; Drug: methylprednisolone; Drug: diphenhydramine; Drug: acetaminophen; Drug: famotidine; Drug: prednisone

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

PLACEBO COMPARATOR

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).

Drug: placebo for elotuzumab; Drug: methylprednisolone; Drug: diphenhydramine; Drug: acetaminophen; Drug: famotidine; Drug: prednisone

Interventions

elotuzumab DRUG

Elotuzumab is a humanized recombinant monoclonal antibody (mAb) targeted against SLAMF7, a cell surface glycoprotein.

Also known as: BMS-901608, Empliciti®

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

placebo for elotuzumab DRUG

The placebo for elotuzumab is 0.9% sterile normal saline for injection.

Also known as: normal saline

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

methylprednisolone DRUG

Premedication administered intravenously, 45 to 90 minutes prior to each elotuzumab/placebo infusion, per protocol. Dosage in milligrams (mg).

Also known as: Solu-Medrol®

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

diphenhydramine DRUG

Premedication administered orally or intravenously, 45 to 90 minutes prior to each elotuzumab/placebo infusion, per protocol. Dosage in milligrams (mg).

Also known as: Benadryl®

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

acetaminophen DRUG

Premedication administered orally, 45 to 90 minutes prior to each elotuzumab/placebo infusion, per protocol. Dosage in milligrams (mg).

Also known as: Tylenol®

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

famotidine DRUG

Premedication administered orally or intravenously, 45 to 90 minutes prior to each elotuzumab/placebo infusion, per protocol. Dosage in milligrams (mg).

Also known as: H2 blocker

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

prednisone DRUG

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).

Also known as: corticosteroid

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator
• Bristol-Myers Squibb: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (3)

Emory Healthcare

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic: Pulmonary and Critical Care Medicine

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• 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.

  PMID: 31796497 BACKGROUND

• 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.

  PMID: 25809420 BACKGROUND

Related Links

• Autoimmunity Centers of Excellence (ACE)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases (NIAID)

MeSH Terms

Conditions

Immunoglobulin G4-Related Disease

Interventions

elotuzumab; Saline Solution; Methylprednisolone; Methylprednisolone Hemisuccinate; Diphenhydramine; Acetaminophen; Famotidine; Histamine H2 Antagonists; Prednisone; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Acetanilides; Anilides; Amides; Aniline Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Pregnadienediols; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Failure to achieve remission along with risk of organ damage with disease flare observed in the Cohort 1b participants led to the conservative decision to stop the trial. Last Cohort 1b visit completed was Week 16; no participants enrolled in Part 2.

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• John H. Stone, MD, MPH

  Massachusetts General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: June 8, 2021
• Study Start: October 13, 2021
• Primary Completion: January 4, 2024
• Study Completion: January 4, 2024
• Last Updated: February 5, 2026
• Results First Posted: February 25, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (3)