Ravulizumab Versus Placebo in Adult Participants With Dermatomyositis

Study Overview
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Brief Summary
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This is a Phase 2/3, double-blind, randomized, placebo-controlled, parallel group, multicenter study to evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of ravulizumab in adult participants with dermatomyositis (DM).

Detailed Description
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The study will be conducted in 2 parts: Part A (Phase 2) and Part B (Phase 3). There will be 3 periods in both Part A and Part B of this study: Screening Period, Randomized Controlled Period, and Open-Label Extension Period.

Official Title
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A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Dermatomyositis

Conditions
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Dermatomyositis

Intervention / Treatment
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* Drug: Ravulizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 18 years of age or older at the time of signing the informed consent. Body weight ≥ 30 kilograms at the time of Screening. Male or female. Diagnosis: Meet 2017 American College of Rheumatology/European League Against Rheumatism classification criteria for definite or probable DM. Participants who have an inadequate response or are intolerant to 1 or more DM treatments, including systemic corticosteroids or immunosuppressive/immunomodulatory therapies (for example, azathioprine, methotrexate, rituximab, intravenous immunoglobulin), either in combination or as monotherapy. Vaccinated against Neisseria meningitidis within 3 years prior to initiating ravulizumab as per national and local guidelines. Participants must receive the vaccination at least 2 weeks before first study intervention. The sponsor recommends that national and local guidelines for prophylactic antibiotics should also be followed. Female participants of childbearing potential and male participants must follow specified contraception guidance as described in the protocol. Key Exclusion Criteria: Participants who have been diagnosed with cancer within the last 3 years need to have appropriate negative cancer screening as per local standard of care within 6 months before Screening (basal or squamous cell skin cancer or carcinoma in situ of the cervix needs to have been excised and without evidence of residual disease for at least 3 months before Screening). Evidence of active malignant disease or malignancies diagnosed within the previous 3 years including hematological malignancies and solid tumors. Participants with other forms of myositis. As per investigator discretion, participants with significant muscle damage (for example, severe muscle atrophy, end stage muscle disease, MRI with severe atrophy or fibrofatty replacement) History of Neisseria meningitidis infection. Human immunodeficiency virus (HIV) infection (evidenced by HIV Type 1 or Type 2 antibody titer). Active systemic bacterial, viral, or fungal infection within 14 days prior to ravulizumab administration. Presence of fever ≥ 38°Celsius (100.4°Fahrenheit) within 7 days prior to study drug administration on Day 1. History of hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab. Pregnant, breastfeeding, or intending to conceive during the course of the study. Inability or unwillingness to adhere to the protocol requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ravulizumab<br>Participants will receive ravulizumab in both Parts A and B. | Drug: Ravulizumab<br>* Intravenous dosing will consist of a loading dose followed by maintenance doses administered every 8 weeks (q8w). The maintenance dosing will be initiated 2 weeks after the loading dose is administered.<br>* Other names: Ultomiris;|
| Placebo Comparator: Placebo<br>Participants will receive placebo in both Parts A and B. | Drug: Placebo<br>* Intravenous dosing will consist of a loading dose followed by maintenance doses administered q8w. The maintenance dosing will be initiated 2 weeks after the loading dose is administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: IMACS-TIS (TIS40) response at Week 26 of the Randomized Controlled Period as per defined composite estimand |  | Week 26 | 
| Part B: IMACS-TIS (TIS40) response at Week 50 of the Randomized Controlled Period as per defined composite estimand |  | Week 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: TIS At Week 26 |  | Week 26 | 
| Part A: Change From Baseline In Cutaneous Dermatomyositis Disease Area And Severity Index (CDASI) Activity Score At Week 26 |  | Baseline, Week 26 | 
| Part A: Response Related to Muscle Enzymes: Normalization Of Most Abnormal Baseline Enzyme At Week 26 |  | Week 26 | 
| Part A: Change From Baseline In Five IMACS Core Set Measures (extra-muscular disease activity based on MDAAT, physician global activity assessment, patient global activity assessment, MMT-8, HAQ) At Week 26 |  | Baseline, Week 26 | 
| Part A: CDASI Response (7-point improvement) at Week 26 | Minimally clinically important differences (MCID) = 7-point improvement. | Baseline through Week 26 | 
| Part A: Cutaneous Dermatomyositis Activity Physician's Global Assessment (CDA-IGA) Response At Week 26 |  | Baseline, Week 26 | 
| Part A: TIS20 Response at Week 26 |  | Week 26 | 
| Part A: TIS60 Response at Week 26 |  | Week 26 | 
| Part A: Time To First Response Of TIS20, TIS40, Or TIS60 |  | Baseline through Week 26 | 
| Part A: Clinical Worsening During Randomized Controlled Period At Two Consecutive Visits |  | Baseline through Week 26 | 
| Part A: Receipt of Rescue Therapy |  | Baseline through Week 26 | 
| Part B: TIS At Week 50 |  | Week 50 | 
| Part B: Change From Baseline In Five IMACS Core Set Measures (extra-muscular disease activity based on MDAAT, physician global activity assessment, patient global activity assessment, MMT-8, HAQ) At Week 50 |  | Baseline, Week 50 | 
| Part B: Change From Baseline In Cutaneous Dermatomyositis Disease Area And Severity Index (CDASI) Activity Score At Week 50 |  | Baseline, Week 50 | 
| Part B: Response Related to Muscle Enzymes: Normalization Of Most Abnormal Baseline Enzyme At Week 50 |  | Week 50 | 
| Part B: CDASI Response (7-point improvement) at Week 50 | Minimally clinically important differences (MCID) = 7-point improvement. | Baseline through Week 50 | 
| Part B: Cutaneous Dermatomyositis Activity Physician's Global Assessment (CDA-IGA) Response At Week 50 |  | Week 50 | 
| Part B: TIS20 Response at Week 50 |  | Week 50 | 
| Part B: TIS60 Response at Week 50 |  | Week 50 | 
| Part B: Time To First Response Of TIS20, TIS40, Or TIS60 |  | Baseline through Week 50 | 
| Part B: Clinical Worsening During Randomized Controlled Period At Two Consecutive Visits |  | Baseline through Week 50 | 
| Part B: Receipt of Rescue Therapy |  | Baseline through Week 50 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ravulizumab, ALXN1210, Ultomiris, Pharmacokinetics, Pharmacodynamics, Efficacy, DM