Ublituximab in Autoantibody Positive Immune Mediated Necrotizing Myopathy

NCT07103746 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT AIM01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 8

Brief Summary

This is a multi-center, Phase 2 trial of ublituximab as first-line combination therapy in early, active autoantibody positive immune-mediated necrotizing myopathy. The primary objective is to estimate the effect of ublituximab as first add-on combination therapy at 24 weeks compared to placebo in treating early, active autoantibody positive immune-mediated necrotizing myopathy using the validated 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Myositis Response Criteria, as measured by the Total Improvement Score (TIS)

Conditions

Autoimmune Disorders

Keywords

Ublituximab; Active Autoantibody Positive Immune-Mediated Necrotizing Myopathy (IMNM); Idiopathic inflammatory myopathies (IIM)

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the Total Improvement Score (TIS) at Week 24 reflecting the change from baseline

  TIS is a composite endpoint based on improvement in the 6 Disease Activity Core Set Measure (CSM) scores and ranges from 0 to 100 (2016 American College of Rheumatology \[ACR\] Myositis Response Criteria/European League Against Rheumatism \[EULAR\]). A higher score indicates more improvement.

  Baseline to Week 24

Secondary Outcomes (15)

• Change in mean Total Improvement Score (TIS) value

  Baseline to weeks 48, 60, and 72

• Proportion of participants achieving minimal improvement response (TIS >= 20 points)

  Baseline to weeks 24, 48, 60 and 72

• Proportion of participants achieving moderate improvement response (TIS >= 40 points)

  Baseline to weeks 24, 48, 60 and 72

• Median Time to achieving minimal improvement response (TIS >= 20 points)

  Baseline to week 24

• Median Time to achieving moderate improvement response (TIS >= 40 points)

  Baseline to week 24

Study Arms (2)

Initial Ublituximab Active Group

EXPERIMENTAL

Receives 150 mg Ublituximab at Day 0 and 450 mg Ublituximab at Week 2, followed by 450 mgs of Ublituximab at Weeks 24 and 48. At Week 26, will receive a Placebo dose of 450 mg to maintain the blind.

Drug: Ublituximab; Drug: Placebo for Ublituximab

Initial Placebo of ublituximab Group

EXPERIMENTAL

Receives 150 mg Placebo at Day 0 and 450 mg Placebo at Week 2. Receives 150 mg Ublituximab at Week 24 followed by 450 mg Ublituximab at Weeks 26 and 48.

Drug: Ublituximab; Drug: Placebo for Ublituximab

Interventions

Ublituximab DRUG

Initial dose includes 150 mg dose followed by 450 mg two weeks later; maintenance dose is 450 mg

Also known as: BRIUMVI(TM)

Initial Placebo of ublituximab Group; Initial Ublituximab Active Group

Placebo for Ublituximab DRUG

0.9% sodium chloride injection

Initial Placebo of ublituximab Group; Initial Ublituximab Active Group

Eligibility Criteria

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

You may qualify if:

• Participant must be able to understand and provide informed consent.
• Age 18 years or older at disease onset.
• Definite or probable IIM per the 2017 EULAR/ACR classification criteria.
• Diagnosis of IMNM, meeting the 2016 ENMC classification criteria and having either of the following antibodies:
• Anti-SRP
• Anti-HMGCR
• Early disease as defined as onset of objective muscle weakness assessed by a physician and/or CK elevation attributed to IMNM within 1 year of the time of informed consent.
• Muscle weakness as assessed by an MMT-8 score \< 142 of 150 and CK \> 1.5x ULN along with abnormality in at least 1 of the following 4 CSMs at screening:
• PhGA ≥ 2 cm
• PtGA ≥ 2 cm
• Extramuscular global assessment ≥ 2 cm
• HAQ-DI ≥ 0.25
• Treatment with only one of the following background immunosuppressant medications for IMNM for at least 12 weeks prior to randomization and the same dose for at least 4 weeks prior to randomization:
• Methotrexate up to 25 mg weekly
• Mycophenolate mofetil up to 3000 mg daily

You may not qualify if:

• End-stage myositis with end-organ involvement that poses additional risk to the participant or confounds the assessment of the participant in the study. Conditions include but are not limited to advanced symptomatic interstitial lung disease (e.g., Forced Vital Capacity (FVC) \<60% and/or requiring oxygen therapy) or severe dysphagia.
• Irreversible muscle involvement and/or severe atrophy that will pose additional risk to the participant or confound the assessment of the participant in the study. This includes Muscle Damage VAS ≥ 3 cm at screening, documented history of severe atrophy of multiple muscle groups (based on MRI), and/or wheelchair bound.
• Uncontrolled interstitial lung disease or any other uncontrolled IIM manifestation that in the opinion of the investigator would be likely to require treatment with prohibited medication during the study.
• Severe liver disease, such as signs of ascites or hepatic encephalopathy.
• History of malignancy (excluding non-melanoma skin cancer) unless cured by adequate treatment, with no evidence of recurrence for ≥ 5 years from the time of informed consent.
• Recent or ongoing bacterial, viral, or fungal infection requiring systemic treatment within 14 days of the time of informed consent.
• Current suppressive therapy for any chronic infections including herpes simplex virus (HSV).
• Infection with Mycobacterium tuberculosis (TB) as defined by any of the following:
• Positive interferon gamma release assay (IGRA) performed at screening or within 12 weeks prior to the time of informed consent.
• 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 purified protein derivative (PPD) skin test. 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 randomization.
• Medical history or serologic evidence at screening of chronic infections, including:
• a. Human immunodeficiency virus (HIV) infection b. Hepatitis B virus (HBV) as indicated by surface antigen or hepatitis B core antibody positivity c. Hepatitis C virus (HCV) 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 they have a negative viral load at Screening.
• Known hypersensitivity reaction to ublituximab.
• Received a live or live-attenuated vaccine \< 4 weeks before the time of informed consent. Received any other type of vaccine \< 2 weeks before the time of informed consent.
• Any of the following laboratory tests at screening:

Sponsors & Collaborators

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

Study Sites (8)

University of Alabama at Birmingham School of Medicine: Division of Clinical Immunology & Rheumatology

Birmingham, Alabama, 35233, United States

NOT YET RECRUITING

Emory University School of Medicine: Division of Rheumatology

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

University of Chicago, Department of Medicine: Rheumatology

Chicago, Illinois, 60637, United States

NOT YET RECRUITING

Johns Hopkins Hospital: Division of Rheumatology

Baltimore, Maryland, 21244, United States

RECRUITING

Mayo Clinic: Division of Rheumatology

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

Northwell Health: Division of Rheumatology and Allergy-Clinical Immunology

Great Neck, New York, 11021, United States

NOT YET RECRUITING

University of Pittsburgh Medical Center: Division of Rheumatology and Clinical Immunology

Pittsburgh, Pennsylvania, 15261, United States

NOT YET RECRUITING

University of Texas - Houston

Houston, Texas, 77030, United States

NOT YET RECRUITING

Related Links

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

MeSH Terms

Conditions

Autoimmune Diseases; Myositis

Interventions

ublituximab

Condition Hierarchy (Ancestors)

Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Julie Paik, M.D., M.H.S.

  Johns Hopkins Hospital: Division of Rheumatology

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: July 21, 2025
• First Posted: August 5, 2025
• Study Start: February 26, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (8)