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

NCT04025632 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: RA101495-02.202
• Study Type: interventional
• Target: 27
• Locations: 4 countries
• Sites: 18

Brief Summary

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.

Conditions

Immune Mediated Necrotizing Myopathy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

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

Secondary Outcomes (8)

• 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

  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

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

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

  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

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

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

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

Study Arms (2)

0.3 mg/kg zilucoplan

EXPERIMENTAL

Daily subcutaneous (SC) injection

Drug: zilucoplan

Placebo

PLACEBO COMPARATOR

Daily subcutaneous (SC) injection

Other: Placebo

Interventions

zilucoplan DRUG

Daily subcutaneous (SC) inection

0.3 mg/kg zilucoplan

Placebo OTHER

Daily subcutaneous (SC) inection

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ra Pharmaceuticals: lead

Study Sites (18)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

University of Florida Health Jacksonville

Jacksonville, Florida, 32209, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

National Institute of Health

Bethesda, Maryland, 20892, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University School of Medicine in Saint Louis

St Louis, Missouri, 63110, United States

Location

Northwell Health Neuroscience Institute

Great Neck, New York, 11021, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Wesley Neurology Clinic

Memphis, Tennessee, 38018, United States

Location

Austin Neuromuscular Center

Austin, Texas, 78756, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Hôpital Universitaire Pitié Salpêtrière

Paris, 75013, France

Location

Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

Location

University College London Hospitals NHS Foundation Trust

London, WC1N3BG, United Kingdom

Location

Salford Royal NHS Barnes Clinical Research Facility

Manchester, M6 8HD, United Kingdom

Location

MeSH Terms

Interventions

zilucoplan

Limitations and Caveats

The study was terminated based on the primary efficacy endpoint analysis after the first data lock.

Results Point of Contact

• Title: Clin Trial Reg & Results Disclosure
• Organization: UCB BIOSCIENCES GmbH

clinicaltrials@ucb.com

Please email

Study Officials

• UCB Cares

  UCB Pharma

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 19, 2019
• Study Start: November 7, 2019
• Primary Completion: March 4, 2021
• Study Completion: June 14, 2021
• Last Updated: July 27, 2022
• Results First Posted: May 16, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

GB (2); FR (1); US (14); NL (1)