Immune Mediated Necrotizing MyopathyPhase 2NCT04025632
Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy
A Phase 2 study testing zilucoplan in people with Immune Mediated Necrotizing Myopathy, run by Ra Pharmaceuticals at 18 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Immune Mediated Necrotizing Myopathy
- What is being tested?
- zilucoplan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 18 sitesin 4 countries
- Study dates
- 7 Nov 2019to 14 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
18 sites in 4 countries.
18 sites in 4 countries
United States14 sites
Austin Neuromuscular Center
Austin, Texas, 78756
National Institute of Health
Bethesda, Maryland, 20892
Brigham and Women's Hospital
Boston, Massachusetts, 02115
The Ohio State University
Columbus, Ohio, 43221
Northwell Health Neuroscience Institute
Great Neck, New York, 11021
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Florida Health Jacksonville
Jacksonville, Florida, 32209
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of California Los Angeles
Los Angeles, California, 90095
Wesley Neurology Clinic
Memphis, Tennessee, 38018
University of California Irvine
Orange, California, 92868
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Washington University School of Medicine in Saint Louis
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33612
United Kingdom2 sites
University College London Hospitals NHS Foundation Trust
London, WC1N3BG
Salford Royal NHS Barnes Clinical Research Facility
Manchester, M6 8HD
About this study
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
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
- Being tested
- zilucoplan, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zilucoplanDrug
Daily subcutaneous (SC) inection
PlaceboOther
Daily subcutaneous (SC) inection
| Study group | Role | What they receive |
|---|---|---|
| 0.3 mg/kg zilucoplan | Experimental | Daily subcutaneous (SC) injection Receives: Drug: zilucoplan |
| Placebo | Placebo comparator | Daily subcutaneous (SC) injection Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Day 1) and end of Main Portion (Week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2019
- Study start7 Nov 2019
- Primary completion4 Mar 2021
- Study completion14 Jun 2021
Why it stopped: The study was terminated based on the primary efficacy endpoint analysis after the first data lock.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Immune Mediated Necrotizing MyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ra Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- UCB Cares, Study director, UCB Pharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04025632
- Sponsor's protocol ID
- RA101495-02.202
- Status last verified
- Jul 2022
- First submitted
- 17 Jul 2019
- Last updated
- 27 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04025632
- Acronym / sponsor ID
- RA101495-02.202
- Conditions
- Immune Mediated Necrotizing Myopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated based on the primary efficacy endpoint analysis after the first data lock.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Ra PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Nov 2019 (actual)
- Primary completion
- 4 Mar 2021 (actual)
- Study completion
- 14 Jun 2021 (actual)
- First posted
- 19 Jul 2019 (actual)
- Results
- Posted 16 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0.3 mg/kg zilucoplan | Experimental | Drug: zilucoplanDaily subcutaneous (SC) injection |
| Placebo | Placebo comparator | Other: PlaceboDaily subcutaneous (SC) injection |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zilucoplanDaily subcutaneous (SC) inection | Drug | 0.3 mg/kg zilucoplan |
| PlaceboDaily subcutaneous (SC) inection | Other | Placebo |
Primary outcome
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.
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.
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
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
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
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
Time frame: Baseline (Day 1) and end of Main Portion (Week 8)
Change From Baseline to Week 8 in Patient Global Activity VAS Score
Time frame: Baseline (Day 1) and end of Main Portion (Week 8)
Change From Baseline to Week 8 in HAQ Score
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
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
Time frame: Baseline (Day 1) and end of Main Portion (Week 8)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UCB Cares study director
UCB Pharma
18 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing zilucoplan in people with Immune Mediated Necrotizing Myopathy, run by Ra Pharmaceuticals at 18 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, United Kingdom, France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2022.