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Safety and Efficacy Study of Zilucoplan in Subjects With Immune-Mediated Necrotizing Myopathy
Phase 2 trial testing zilucoplan in Immune Mediated Necrotizing Myopathy in 27 participants. Terminated before completion.
| Lead sponsor | Ra Pharmaceuticals |
|---|---|
| Phase | Phase 2 |
| Status | Terminated |
| Study type | INTERVENTIONAL |
| Allocation | randomized |
| Design | parallel |
| Masking | quadruple |
| Primary purpose | treatment |
| Enrollment | 27 |
| Start date | 7 November 2019 |
| Primary completion | 4 March 2021 |
| Estimated completion | 14 June 2021 |
| Sites | 18 locations across France, Netherlands, United States, United Kingdom |
Ra Pharmaceuticals — full company profile →
Adults 18 to 75, any sex, with Immune Mediated Necrotizing Myopathy. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
All laboratory samples were obtained prior to administration of study drug at applicable visits. CK levels were measured by a central laboratory.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -20.72 | ± 31.22 |
| Zilucoplan 0.3 mg/kg | -9.86 | ± 26.06 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Main Portion: Placebo | 13 | |
| Main Portion: Zilucoplan 0.3 mg/kg | 9 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 7 | |
| Zilucoplan 0.3 mg/kg | 6 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -0.712 | ± 0.789 |
| Zilucoplan 0.3 mg/kg | -1.401 | ± 0.788 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -0.18 | ± 3.44 |
| Zilucoplan 0.3 mg/kg | 3.71 | ± 3.81 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -0.626 | ± 0.557 |
| Zilucoplan 0.3 mg/kg | -0.830 | ± 0.671 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -0.685 | ± 0.707 |
| Zilucoplan 0.3 mg/kg | -1.966 | ± 0.854 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 0.022 | ± 0.151 |
| Zilucoplan 0.3 mg/kg | -0.125 | ± 0.183 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -0.144 | ± 0.336 |
| Zilucoplan 0.3 mg/kg | -0.287 | ± 0.398 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 3.45 | ± 3.41 |
| Zilucoplan 0.3 mg/kg | 8.98 | ± 4.08 |
Time frame: Baseline (Day 1) to End of Safety Follow-up (Week 83). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Main Portion: Placebo | Main Portion: Zilucoplan 0… | Extension Portion: Zilucop… |
|---|---|---|---|---|
| COVID-19 | Infections and infestations | — | — | — |
| Ventricular tachycardia | Cardiac disorders | — | — | — |
| Rectal haemorrhage | Gastrointestinal disorders | — | — | — |
| Asthenia | General disorders | — | — | — |
| Sinusitis bacterial | Infections and infestations | — | — | — |
| Staphylococcal sepsis | Infections and infestations | — | — | — |
| Rhinovirus infection | Infections and infestations | — | — | — |
| Urinary tract infection | Infections and infestations | — | — | — |
| Liver function test increased | Investigations | — | — | — |
| Muscular weakness | Musculoskeletal and connective tissue disorders | — | — | — |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | — | — | — |
| Reaction | System | Main Portion: Placebo | Main Portion: Zilucoplan 0… | Extension Portion: Zilucop… |
|---|---|---|---|---|
| Headache | Nervous system disorders | — | — | — |
| Nausea | Gastrointestinal disorders | — | — | — |
| Fall | Injury, poisoning and procedural complications | — | — | — |
| Anaemia | Blood and lymphatic system disorders | — | — | — |
| Vertigo | Ear and labyrinth disorders | — | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — | — |
| Arthralgia | Musculoskeletal and connective tissue disorders | — | — | — |
| Palpitations | Cardiac disorders | — | — | — |
| Sinus tachycardia | Cardiac disorders | — | — | — |
| Constipation | Gastrointestinal disorders | — | — | — |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | — | — | — |
| Faeces soft | Gastrointestinal disorders | — | — | — |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — |
| Injection site pain | General disorders | — | — | — |
| Injection site pruritus | General disorders | — | — | — |
| Influenza like illness | General disorders | — | — | — |
| Injection site erythema | General disorders | — | — | — |
| Oedema peripheral | General disorders | — | — | — |
| Fatigue | General disorders | — | — | — |
| Injection site bruising | General disorders | — | — | — |
| Vaccination site pain | General disorders | — | — | — |
| Vessel puncture site bruise | General disorders | — | — | — |
| Sinusitis | Infections and infestations | — | — | — |
| Conjunctivitis | Infections and infestations | — | — | — |
| Nasopharyngitis | Infections and infestations | — | — | — |
| Urinary tract infection pseudomonal | Infections and infestations | — | — | — |
| Contusion | Injury, poisoning and procedural complications | — | — | — |
| Skin procedural complication | Injury, poisoning and procedural complications | — | — | — |
| Lipase increased | Investigations | — | — | — |
| Lymphocyte count decreased | Investigations | — | — | — |
| Amylase increased | Investigations | — | — | — |
| Weight decreased | Investigations | — | — | — |
| White blood cell count decreased | Investigations | — | — | — |
| Blood bilirubin increased | Investigations | — | — | — |
| Blood glucose increased | Investigations | — | — | — |
| Blood pressure increased | Investigations | — | — | — |
| Gamma-glutamyltransferase increased | Investigations | — | — | — |
| Decreased appetite | Metabolism and nutrition disorders | — | — | — |
| Myalgia | Musculoskeletal and connective tissue disorders | — | — | — |
Most-reported serious reactions: COVID-19, Ventricular tachycardia, Rectal haemorrhage, Asthenia, Sinusitis bacterial, Staphylococcal sepsis, Rhinovirus infection, Urinary tract infection.
Data from ClinicalTrials.gov NCT04025632 adverse events section.
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.
8 peer-reviewed publications reference this trial (live from Europe PMC):
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Trials by the same sponsor.
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