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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04025632
Recruitment Status : Terminated (The study was terminated based on the primary efficacy endpoint analysis after the first data lock.)
First Posted : July 19, 2019
Results First Posted : May 16, 2022
Last Update Posted : July 27, 2022
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( Ra Pharmaceuticals )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Immune Mediated Necrotizing Myopathy Drug: zilucoplan Other: Placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy
Actual Study Start Date : November 7, 2019
Actual Primary Completion Date : March 4, 2021
Actual Study Completion Date : June 14, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Muscle Disorders

Arms and Interventions
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Arm Intervention/treatment
Experimental: 0.3 mg/kg zilucoplan
Daily subcutaneous (SC) injection
 Drug: zilucoplan
Daily subcutaneous (SC) inection
Placebo Comparator: Placebo
Daily subcutaneous (SC) injection
 Other: Placebo
Daily subcutaneous (SC) inection


Outcome Measures
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Primary Outcome Measures :
  1. Percentage Change From Baseline to Week 8 in Serum Creatine Kinase (CK) Levels [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    All laboratory samples were obtained prior to administration of study drug at applicable visits. CK levels were measured by a central laboratory.

  2. Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) [ Time Frame: Baseline (Day 1) to end of Main Portion (Week 8) ]

    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    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.

  2. Change From Baseline to Week 8 in Triple Timed Up and Go Test (3TUG) Time [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    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.

  3. Change From Baseline to Week 8 in Proximal Manual Muscle Testing (MMT) Score [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    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.

  4. Change From Baseline to Week 8 in Physician Global Activity Visual Analogue Scale (VAS) Score [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    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.

  5. Change From Baseline to Week 8 in Patient Global Activity VAS Score [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    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.

  6. Change From Baseline to Week 8 in HAQ Score [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    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.

  7. Change From Baseline to Week 8 in MDAAT Extramuscular Disease Activity VAS Score [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    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.

  8. Change From Baseline to Week 8 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score [ Time Frame: Baseline (Day 1) and end of Main Portion (Week 8) ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04025632


Locations
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Sponsors and Collaborators
Ra Pharmaceuticals
Investigators
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Study Director: UCB Cares UCB Pharma
  Study Documents (Full-Text)

Documents provided by UCB Pharma ( Ra Pharmaceuticals ):
Study Protocol  [PDF] February 16, 2021
Statistical Analysis Plan  [PDF] June 9, 2021

More Information
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Responsible Party: Ra Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04025632    
Other Study ID Numbers: RA101495-02.202
First Posted: July 19, 2019    Key Record Dates
Results First Posted: May 16, 2022
Last Update Posted: July 27, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, 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 prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: http://www.Vivli.org

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases