Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy

Phase 2TerminatedNCT04025632

Ra Pharmaceuticals27 enrolled

Overview

The purpose of the study is to evaluate the safety and efficacy of zilucoplan in patients with Immune-Mediated Necrotizing Myopathy (IMNM). Subjects will be randomized in a 1:1 ratio to receive daily SC doses of 0.3 mg/kg zilucoplan or matching placebo for 8 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Immune Mediated Necrotizing Myopathy

Interventions

zilucoplanDRUG

Daily subcutaneous (SC) inection

PlaceboOTHER

Daily subcutaneous (SC) inection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Clinical diagnosis of IMNM (Immune-Mediated Necrotizing Myopathy) * Positive serology for anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) or anti-signal recognition particle (SRP) autoantibodies * Clinical evidence of weakness (≤ grade 4 out of 5) on manual muscle testing in at least one proximal limb muscle group * Creatine kinase (CK) of \>1000 U/L at Screening * No change in corticosteroid dose for at least 30 days prior to Baseline or anticipated to occur during the first 8-weeks on study * No changes in immunosuppressive therapy, including dose, for at least 30 days prior to Baseline or anticipated to occur during the first 8-weeks on study Exclusion Criteria: * History of meningococcal disease * Current or recent systemic infection within 2 weeks prior to Screening or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Screening * Recent initiation of intravenous immunoglobulin (IVIG) (i.e., first cycle administered less than 90 days prior to Baseline) * Rituximab use within 90 days prior to Baseline or anticipated to occur during study * Statin use within 30 days prior to Baseline or anticipated to occur during study * Plasma exchange within 4 weeks prior to Baseline or expected to occur during the 8-week Treatment Period

Locations (18)

University of California Los Angeles

Los Angeles, California, United States

University of California Irvine

Orange, California, United States

Outcomes

Primary Outcomes

Percentage Change From Baseline to Week 8 in Serum Creatine Kinase (CK) Levels

All laboratory samples were obtained prior to administration of study drug at applicable visits. CK levels were measured by a central laboratory.

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)

Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)

A TEAE was defined as: * An adverse event (AE) that occurred after study treatment start that was not present at the time of treatment start. * An AE that increased in severity after treatment start if the event was present at the time of treatment start.

Time frame: Baseline (Day 1) to end of Main Portion (Week 8)

Secondary Outcomes

Number of Participants Who Achieve at Least Minimal Response Based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Response Criteria Scale

The ACR/EULAR scale utilized a conjoint analysis-based continuous model using absolute percent change from Baseline in core set measures (physician, patient, and Myositis Disease Activity Assessment Tool (MDAAT); muscle strength; Health Assessment Questionnaire (HAQ); and muscle enzyme levels). A total improvement score (range 0-100) was determined by summing scores for each core set measure and comparing improvement in each respective core set measure. The threshold for minimal improvement was ≥20 in the total improvement score with higher scores indicating a better outcome.

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)

Change From Baseline to Week 8 in Triple Timed Up and Go Test (3TUG) Time

The 3TUG test involved the ambulatory participant getting up from a seated position in a chair, walking at their normal pace for 3 meters, turning around, walking back to the chair, and sitting down. This sequence was repeated 3 times without rest, and the 3TUG test time is the average of the 3 lap times. A negative change from baseline indicated a better outcome.

Data from ClinicalTrials.gov

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University of Florida Health Jacksonville

Jacksonville, Florida, United States

University of South Florida

Tampa, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

National Institute of Health

Bethesda, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Washington University School of Medicine in Saint Louis

St Louis, Missouri, United States

Northwell Health Neuroscience Institute

Great Neck, New York, United States

The Ohio State University

Columbus, Ohio, United States

...and 8 more locations

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)

Change From Baseline to Week 8 in Proximal Manual Muscle Testing (MMT) Score

The proximal MMT assessed muscle strength using manual muscle testing in 7 muscle groups (left and right sides assessed separately). The total MMT score for this study, inclusive of both sides, could range from 0-140, where 0 means no strength in any muscles and 140 means full strength in all the muscles examined. A negative change from Baseline indicated a worse outcome.

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)

Change From Baseline to Week 8 in Physician Global Activity Visual Analogue Scale (VAS) Score

The Physician Global Activity VAS Score measured the treating physician's global evaluation of the participant's overall disease activity using a 10 cm VAS labelled with "no activity" at the left end and "maximum activity" at the right end. The Physician Global Activity VAS Score ranged from 0 (absent extramuscular disease activity) to 10 (maximum extramuscular disease activity). A negative change from Baseline indicated a better outcome.

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)

Change From Baseline to Week 8 in Patient Global Activity VAS Score

The Patient Global Activity VAS Score measured the treating participant's global evaluation of their overall disease activity using a 10 cm VAS labelled with "no activity" at the left end and "maximum activity" at the right end. The Patient Global Activity VAS score ranged from 0 (absent extramuscular disease activity) to 10 (maximum extramuscular disease activity). A negative change from Baseline indicated a better outcome.

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)

Change From Baseline to Week 8 in HAQ Score

The HAQ had 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities with 2 to 3 questions for each section. Scoring within each section ranged from 0 (without any difficulty) to 3 (unable to do). The total HAQ score was then calculated by summing the scores and dividing by the number of categories answered. The total HAQ score for this study could range from 0-3, where 0 means no functional impairment and 3 means complete functional impairment. A negative change from Baseline indicated a better outcome.

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)

Change From Baseline to Week 8 in MDAAT Extramuscular Disease Activity VAS Score

The MDAAT extramuscular disease activity VAS score measured the degree of disease activity of extramuscular organ systems and muscle. The scoring was performed by the physician and ranged from 0 (absent extramuscular disease activity) to 10 (maximum extramuscular disease activity). A negative change from Baseline indicated a better outcome.

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)

Change From Baseline to Week 8 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score

The FACIT-Fatigue Scale is a 13-item tool which measured an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue was measured on a 4-point Likert scale. The total FACIT-Fatigue Scale score for this study could range from 0-52, where 0 means the participants were very much fatigued during their usual daily activities and 52 means the participants were not at all fatigued during their usual daily activities. A negative change from Baseline indicated a worse outcome.

Time frame: Baseline (Day 1) and end of Main Portion (Week 8)