Ravulizumab Versus Placebo in Adult Participants With Dermatomyositis

• ClinicalTrials.gov Identifier: NCT04999020
• Recruitment Status: Recruiting
• First Posted: August 10, 2021
• Last Update Posted: April 14, 2022
• Sponsor: Alexion Pharmaceuticals
• Information provided by (Responsible Party): Alexion Pharmaceuticals

Tracking Information

• First Submitted Date: August 4, 2021
• First Posted Date: August 10, 2021
• Last Update Posted Date: April 14, 2022
• Actual Study Start Date: December 2, 2021
• Estimated Primary Completion Date: August 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 4, 2021)

• Part A: Proportion Of Participants With A ≥ 20-point Improvement Response On International Myositis Assessment And Clinical Studies-Total Improvement Score (IMACS-TIS) (TIS20) At Week 26 Of The Randomized Controlled Period [ Time Frame: Week 26 ]
• Part B: Proportion Of Participants With A ≥ 20-point Improvement Response On TIS20 At Week 50 [ Time Frame: Week 50 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 2, 2021)

• Part A: Mean TIS At Week 26 [ Time Frame: Week 26 ]
• Part A: Mean Change From Baseline In Cutaneous Dermatomyositis Disease Area And Severity Index (CDASI) Activity Score At Week 26 [ Time Frame: Baseline, Week 26 ]
• Part A: Change From Baseline Of Each Of The IMACS Core Set Measures At Week 26 [ Time Frame: Baseline, Week 26 ]
• Part A: Time To First CDASI Activity Score Improvement [ Time Frame: Baseline through Week 26 ]
  Minimally clinically important differences (MCID) = 7-point improvement.
• Part A: Proportion Of Participants With CDASI MCID Improvement At Week 26 [ Time Frame: Week 26 ]
• Part A: Change In Cutaneous Dermatomyositis Activity Physician's Global Assessment (CDA-IGA) At Week 26 [ Time Frame: Baseline, Week 26 ]
• Part A: Proportion Of Participants With TIS20 At Each Visit [ Time Frame: Baseline through Week 26 ]
• Part A: Proportion Of Participants With A ≥ 40-point Improvement Response On IMACS-TIS (TIS40) At Each Visit [ Time Frame: Baseline through Week 26 ]
• Part A: Proportion Of Participants With A ≥ 60-point Improvement Response On IMACS-TIS (TIS60) At Each Visit [ Time Frame: Baseline through Week 26 ]
• Part A: Time To First Response Of TIS20, TIS40, Or TIS60 [ Time Frame: Baseline through Week 26 ]
• Part A: Time To First IMACS Myositis Core Set Measure Improvements [ Time Frame: Baseline through Week 26 ]
• Part B: Mean TIS At Week 50 [ Time Frame: Week 50 ]
• Part B: Mean Change From Baseline In Manual Muscle Testing Subset Of 8 Muscles (MMT-8) At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Extra-muscular Disease Activity Based On Myositis Disease Activity Assessment Tool (MDAAT) At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In CDASI Activity Score At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Patient Global Activity Assessment At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Physician Global Activity Assessment At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Health Assessment Questionnaire (HAQ) At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Muscle Enzyme Values At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean TIS At Each Visit From Week 2 Through Week 50 [ Time Frame: Week 2 through Week 50 ]
• Part B: Proportion Of Participants With TIS20 At Each Visit [ Time Frame: Baseline through Week 50 ]
• Part B: Proportion Of Participants With TIS40 At Each Visit [ Time Frame: Baseline through Week 50 ]
• Part B: Proportion Of Participants With TIS60 At Each Visit [ Time Frame: Baseline through Week 50 ]
• Part B: Time To First Response Of TIS20, TIS40, Or TIS60 [ Time Frame: Baseline through Week 50 ]
• Part B: Time To First IMACS Myositis Core Set Measure Improvements [ Time Frame: Baseline through Week 50 ]
• Part B: Time To First CDASI Activity Score Improvement [ Time Frame: Baseline through Week 50 ]
  MCID = 7-point improvement
• Part B: Proportion Of Participants With CDASI MCID Improvement At Week 50 [ Time Frame: Week 50 ]
• Part B: Change In CDA-IGA At Week 50 [ Time Frame: Week 50 ]

Original Secondary Outcome Measures (submitted: August 4, 2021)

• Part A: Mean TIS At Week 26 [ Time Frame: Week 26 ]
• Part A: Mean Change From Baseline In Cutaneous Dermatomyositis Disease Area And Severity Index (CDASI) Activity Score At Week 26 [ Time Frame: Baseline, Week 26 ]
• Part A: Change From Baseline Of Each Of The IMACS Core Set Measures At Week 26 [ Time Frame: Baseline, Week 26 ]
• Part A: Time To First CDASI Activity Score Improvement [ Time Frame: Baseline through Week 26 ]
  Minimally clinically important differences (MCID) = 7-point improvement.
• Part A: Proportion Of Participants With CDASI MCID Improvement At Week 26 [ Time Frame: Week 26 ]
• Part A: Change In Investigator Global Assessment Scale For Skin Activity (IGA-SA) At Week 26 [ Time Frame: Baseline, Week 26 ]
• Part A: Proportion Of Participants With TIS20 At Each Visit [ Time Frame: Baseline through Week 26 ]
• Part A: Proportion Of Participants With A ≥ 40-point Improvement Response On IMACS-TIS (TIS40) At Each Visit [ Time Frame: Baseline through Week 26 ]
• Part A: Proportion Of Participants With A ≥ 60-point Improvement Response On IMACS-TIS (TIS60) At Each Visit [ Time Frame: Baseline through Week 26 ]
• Part A: Time To First Response Of TIS20, TIS40, Or TIS60 [ Time Frame: Baseline through Week 26 ]
• Part A: Time To First IMACS Myositis Core Set Measure Improvements [ Time Frame: Baseline through Week 26 ]
• Part B: Mean TIS At Week 50 [ Time Frame: Week 50 ]
• Part B: Mean Change From Baseline In Manual Muscle Testing Subset Of 8 Muscles (MMT-8) At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Extra-muscular Disease Activity Based On Myositis Disease Activity Assessment Tool (MDAAT) At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In CDASI Activity Score At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Patient Global Activity Assessment At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Physician Global Activity Assessment At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Health Assessment Questionnaire (HAQ) At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean Change From Baseline In Muscle Enzyme Values At Week 50 [ Time Frame: Baseline, Week 50 ]
• Part B: Mean TIS At Each Visit From Week 2 Through Week 50 [ Time Frame: Week 2 through Week 50 ]
• Part B: Proportion Of Participants With TIS20 At Each Visit [ Time Frame: Baseline through Week 50 ]
• Part B: Proportion Of Participants With TIS40 At Each Visit [ Time Frame: Baseline through Week 50 ]
• Part B: Proportion Of Participants With TIS60 At Each Visit [ Time Frame: Baseline through Week 50 ]
• Part B: Time To First Response Of TIS20, TIS40, Or TIS60 [ Time Frame: Baseline through Week 50 ]
• Part B: Time To First IMACS Myositis Core Set Measure Improvements [ Time Frame: Baseline through Week 50 ]
• Part B: Time To First CDASI Activity Score Improvement [ Time Frame: Baseline through Week 50 ]
  MCID = 7-point improvement
• Part B: Proportion Of Participants With CDASI MCID Improvement At Week 50 [ Time Frame: Week 50 ]
• Part B: Change In IGA-SA At Week 50 [ Time Frame: Week 50 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ravulizumab Versus Placebo in Adult Participants With Dermatomyositis
• Official Title: 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
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Dermatomyositis

Intervention

• Drug: Ravulizumab
  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.
  Other Names:

  • ALXN1210
  • Ultomiris
• Drug: Placebo
  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.

Study Arms

• Experimental: Ravulizumab
  Participants will receive ravulizumab in both Parts A and B.
  Intervention: Drug: Ravulizumab
• Placebo Comparator: Placebo
  Participants will receive placebo in both Parts A and B.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 4, 2021): 180
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2024
• Estimated Primary Completion Date: August 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 American College of Rheumatology/European League Against Rheumatism classification criteria for definite or probable DM.
• Participants who have an inadequate response (that is, continued impairment by medical doctor report) or are intolerant to 2 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:

• Cancer-associated myositis, defined as the diagnosis of myositis within 3 years of the diagnosis of cancer (except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and 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.
• Participants with significant muscle damage (for example, severe muscle atrophy, end stage muscle disease) as per investigator opinion.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Alexion Pharmaceuticals, Inc.; 1-855-752-2356; clinicaltrials@alexion.com

• Listed Location Countries: France, Germany, Italy, Japan, Korea, Republic of, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04999020
• Other Study ID Numbers: ALXN1210-DM-310; 2021-001200-15 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Alexion Pharmaceuticals
• Study Sponsor: Alexion Pharmaceuticals
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Alexion Pharmaceuticals
• Verification Date: April 2022