Belimumab in Idiopathic Inflammatory Myositis

NCT02347891 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 14-621
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the trial is to evaluate the efficacy and safety of belimumab as a maintenance therapy in adults with refractory Idiopathic inflammatory myositis (IIM) as compared with standard of care. This is a multicentre double-blind, placebo-controlled trial.

Conditions

Myositis

Keywords

Inflammatory Myositis; Dermatomyositis; Polymyositis; Muscle Pain; Myositis; Refractory myositis

Outcome Measures

Primary Outcomes (2)

• Response Rate During Randomized Phase

  Definition of Improvement (DOI) is ≥ 20% of improvement in any 3 of the core set measures (CSM) - Manual Muscle Testing, Patient Global , Physician Global, Muscle Enzyme change , HAQ and Extra- muscular activity and no more than 2 CSM worsening by ≥ 25% (excluding MMT). Total Improvement Score ( TIS) is a sum of weighted scores of absolute change of core set measures ( MMT, Patient Global , Physician Global, Muscle Enzyme change , HAQ and Extra-muscluar activity ). The scores range from 0 to 100, with higher scores indicating greater improvement. TIS ≥ 40 indicates a moderate response and ≥ 60 TIS indicates a major response.

  40 weeks

• Mean Total Improvement Score (TIS) During Randomized Phase

  It is a composite measure calculated as a sum of weighted scores assigned to absolute changes for each measure (MMT , Patient Global, Physician Global, Muscle enzymes, Extramuscluar activity and HAQ) . Total score could range from 0 to 100. TIS ≥ 20 indicates minimal improvement, TIS ≥ 40 indicates moderate response and TIS ≥ 60 indicates a major response. 2016 ACR/EULAR Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis and Juvenile Dermatomyositis (Aggarwal R et al 2016)

  40 Week

Secondary Outcomes (2)

• Response Rate After Open Label Phase

  64 weeks

• Mean Total Improvement Score (TIS) After Open Label Phase

  64 Week

Study Arms (2)

Belimumab + Standard of Care

EXPERIMENTAL

Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period. Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)

Drug: Belimumab

Placebo + Standard of Care

ACTIVE COMPARATOR

Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period. Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).

Drug: Placebo

Interventions

Belimumab DRUG

Randomized phase: Week 0 - Week 40

Also known as: Benlysta

Belimumab + Standard of Care

Placebo DRUG

Randomized phase: Week 0 - Week 40

Also known as: Saline IV bag

Placebo + Standard of Care

Eligibility Criteria

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

You may qualify if:

• Adults \>18 years of age
• Have a diagnosis of:
• definite or probable dermatomyositis (DM) or
• Definite or probable diagnosis of polymyositis (PM) with presence of one of myositis specific antibodies. In the absence of myositis specific auto-antibodies, the diagnosis of PM will require review of the muscle biopsy and adjudication by the predetermined committee of experts.
• Presence of positive autoantibody (ANA \>1:80 or RNP or SSA/SSB or any of the myositis specific autoantibody: antisynthetase autoantibodies (anti-Jo-1, PL-7, PL-12, EJ, OJ, KS), anti-SRP, anti-Mi-2, anti-p140).
• Have refractory IIM as defined by inadequate response or intolerance to at least 3 months of glucocorticoids and/or at least one other immunosuppressive agent, such as azathioprine, methotrexate, IVIG, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine cyclophosphamide, and Rituximab.
• Have active IIM at screening. This requires at least 3 criteria from the CSM
• Dermatomyositis patients that do not meet the MMT criteria, must have:
• a cutaneous VAS score of \>3 cm on a 10 cm VAS scale (MDAAT) will be required:
• elevation of at least one muscle enzyme (creatine kinase \[CK\]; aldolase; lactate dehydrogenase \[LDH\]; alanine aminotransferase \[ALT\]; or aspartate aminotransferase \[AST\]) to a minimum level of 1.3 times the upper limit of normal,
• and 1 additional core set measure
• For patients with ≥ 7 years of IIM, muscle biopsy or muscle MRI within 4 months prior to enrollment will be required to document active myositis to avoid enrolling patients with significant index of damage/ muscle atrophy. This is not applicable to DM patients with a cutaneous VAS score of \>3 cm on a 10 cm VAS scale (MDAAT).
• Have a stable background glucocorticoid therapy for at least 2 weeks prior to screening (Prednisone (or equivalent) dose \< 15 mg daily)
• Have a stable immunosuppressive therapy (IS) (azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine for \> 2 months prior to screening. Patients on intravenous gamma globulin (IVIG) have to be on a stable dose and frequency regimen for ≥ 3 months.
• Have the ability to understand the requirements of the study and provide written informed consent (including consent for the use and disclosure of research-related health information) and comply with the study protocol procedures (including required study visits)

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• Have severe muscle damage as defined by a Muscle Damage Index (MDI) \> 5.0 cm using a visual analogue scale (VAS) 10.0 cm in length or evidence of severe muscle atrophy on muscle MRI.
• History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell).
• Have a history of a primary immunodeficiency
• Have a significant IgG deficiency (IgG level \< 400 mg/dl) Have an IgA deficiency (IgA level \< 10 mg/dL)
• Discontinuation IS agent \< 3 months prior to Screening. Including: azathioprine, methotrexate, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine, or intravenous gamma globulin \[IVIG\]
• Have received Rituximab within 365 days prior to Screening.
• Have received cyclophosphamide within 180 days prior to Screening
• Have received treatment with:
• Initiated IVIG 3 months prior to Screening
• Pulse steroids 2 months prior to Screening
• Have received treatment with Belimumab at any time prior to Screening
• Have received a biologic investigational agent within 365 days prior to Screening.
• Have received a non-biologic investigational agent within 30 days or 5 half-lives of the agent (whichever is longer) prior to Screening.
• Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.

Sponsors & Collaborators

• Northwell Health: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Northwell Health Divison of Rheumatology

Great Neck, New York, 11021, United States

Location

Related Publications (1)

• Marder G, Quach T, Chadha P, Nandkumar P, Tsang J, Levine T, Schiopu E, Furie R, Davidson A, Narain S. Belimumab treatment of adult idiopathic inflammatory myopathy. Rheumatology (Oxford). 2024 Mar 1;63(3):742-750. doi: 10.1093/rheumatology/kead281.

  PMID: 37326854 DERIVED

MeSH Terms

Conditions

Myositis; Dermatomyositis; Polymyositis; Myalgia

Interventions

belimumab

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Musculoskeletal Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Principal Investigator
• Organization: Northwell Health

gmarder@northwell.edu

5167082550

Study Officials

• Galina Marder, MD

  Northwell.edu

  PRINCIPAL INVESTIGATOR

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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Inflammatory Muscle Disease and Vasculitis Center

Study Record Dates

• First Submitted: January 22, 2015
• First Posted: January 28, 2015
• Study Start: January 1, 2015
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: February 9, 2024
• Results First Posted: February 9, 2024

Record last verified: 2024-01

Locations

US (1)