E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune-Mediated Necrotizing Myopathy |
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E.1.1.1 | Medical condition in easily understood language |
Immune-Mediated Necrotizing Myopathy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072156 |
E.1.2 | Term | Immune-mediated necrotizing myopathy |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the safety and tolerability of zilucoplan in subjects with IMNM
• To evaluate the efficacy of zilucoplan in subjects with IMNM |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for this study, subjects must meet ALL of the following inclusion criteria:
1. Clinical diagnosis of IMNM (Immune-Mediated Necrotizing Myopathy).
2. Positive serology for anti-HMGCR or anti-SRP autoantibodies.
3. Clinical evidence of weakness (≤ grade 4 out of 5) on manual muscle testing in at least one proximal limb muscle group.
4. CK (creatine kinase) of >1000 U/L at Screening.
5. No change in corticosteroid dose for at least 30 days prior to Baseline or anticipated to occur during the first 8-weeks on study.
6. 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.
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E.4 | Principal exclusion criteria |
Subjects who meet ANY of the following exclusion criteria must be excluded from the study:
1. History of meningococcal disease.
2. Current or recent systemic infection within 2 weeks prior to Screening or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Screening.
3. Statin use within 30 days prior to Baseline or anticipated to occur during study.
4. Rituximab use within 90 days prior to Baseline or anticipated to occur during study.
5. Recent initiation of intravenous immunoglobulin (IVIG) (i.e., first cycle administered less than 90 days prior to Baseline).
6. Plasma exchange within 4 weeks prior to Baseline or expected to occur during the 8-week Treatment Period.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint:
• Percent change from Baseline to Week 8 in CK levels. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints:
• Change from Baseline to Week 8 in Triple Timed Up and Go (3TUG) Test (in ambulatory subjects only)
• Change from Baseline to Week 8 in Proximal Manual Muscle Testing (MMT)
• Change from Baseline to Week 8 in Physician Global Activity Visual Analogue Scale (VAS)
• Change from Baseline to Week 8 in Patient Global Activity VAS
• Change from Baseline to Week 8 in Health Assessment Questionnaire (HAQ)
• Change from Baseline to Week 8 in Myositis Disease Activity Assessment Tool (MDAAT) Score
• Change from Baseline to Week 8 in American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Response Criteria
• Change from Baseline to Week 8 in FACIT-Fatigue Scale
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Netherlands |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |