Ravulizumab Versus Placebo in Adult Participants With Dermatomyositis

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

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).

Study Overview

• Status: Terminated
• Conditions: Dermatomyositis
• Intervention / Treatment: Drug: Ravulizumab; Drug: Placebo

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
• Enrollment (Actual): 38
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Research Site
  • Murdoch, Australia, WA6150
    • Research Site
• Brazil
  • Belo Horizonte, Brazil, 30150-221
    • Research Site
  • Belém, Brazil, 66095-055
    • Research Site
  • Campinas, Brazil, 13083
    • Research Site
  • Juiz de Fora, Brazil, 36010-570
    • Research Site
  • Natal, Brazil, 59025-050
    • Research Site
  • Porto Alegre, Brazil, 90035-000
    • Research Site
  • Porto Alegre, Brazil, 90480-000
    • Research Site
  • Salvador, Brazil, 40150-150
    • Research Site
  • Sao Jose Do Rio Preto, Brazil, 15090-000
    • Research Site
  • Serra, Brazil, 29160-750
    • Research Site
  • São Paulo, Brazil, 01308-050
    • Research Site
  • São Paulo, Brazil, 05403-010
    • Research Site
  • Vitória, Brazil, 29050-400
    • Research Site
• France
  • Lille, France, 59037
    • Research Site
  • Lyon, France, 69437
    • Research Site
  • Nantes cedex 1, France, 44093
    • Research Site
  • Paris, France, 75010
    • Research Site
  • Paris Cedex 13, France, 75651
    • Research Site
  • Strasbourg, France, 67098
    • Research Site
  • Toulouse, France, 31059
    • Research Site
• Germany
  • Duesseldorf, Germany, 40225
    • Research Site
  • Erlangen, Germany, 91054
    • Research Site
  • Essen, Germany, 45147
    • Research Site
  • Freiburg im Breisgau, Germany, 79106
    • Research Site
  • Goettingen, Germany, 37075
    • Research Site
  • Halle, Germany, 06120
    • Research Site
  • Jena, Germany, 07747
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Brescia, Italy, 25123
    • Research Site
  • Catania, Italy, 95123
    • Research Site
  • Firenze, Italy, 50134
    • Research Site
  • Jesi, Italy, 60035
    • Research Site
  • Messina, Italy, 98124
    • Research Site
  • Milano, Italy, 20132
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
  • Pisa, Italy, 56126
    • Research Site
  • Reggio Emilia, Italy, 42122
    • Research Site
  • Roma, Italy, 00168
    • Research Site
  • Roma, Italy, 00128
    • Research Site
  • Rome, Italy, 00189
    • Research Site
  • Rozzano, Italy, 20089
    • Research Site
  • Siena, Italy, 53100
    • Research Site
  • Torino, Italy, 10126
    • Research Site
  • Torrette AN, Italy, 60126
    • Research Site
  • Udine, Italy, 33100
    • Research Site
  • Verona, Italy, 37126
    • Research Site
• Japan
  • Bunkyo-ku, Japan, 113-8655
    • Research Site
  • Hiroshima-shi, Japan, 734-8551
    • Research Site
  • Iruma-Gun, Japan, 350-0495
    • Research Site
  • Nagoya-shi, Japan, 467-8602
    • Research Site
  • Narita-shi, Japan, 286-8520
    • Research Site
  • Okayama, Japan, 700-8558
    • Research Site
  • Osaka, Japan, 565-0871
    • Research Site
  • Sapporo-shi, Japan, 060-8648
    • Research Site
  • Sendai-shi, Japan, 980-8574
    • Research Site
  • Urayasu-shi, Japan, 279-0021
    • Research Site
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Research Site
  • Jung-gu, Korea, Republic of, 22332
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 02447
    • Research Site
  • Seoul, Korea, Republic of, 04763
    • Research Site
  • Seoul, Korea, Republic of, 6591
    • Research Site
• Poland
  • Warszawa, Poland, 02-637
    • Research Site
• Spain
  • A Coruna, Spain, 15006
    • Research Site
  • Barakaldo, Spain, 48903
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Bilbao (Vizcaya), Spain, 48013
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08907
    • Research Site
  • Las Palmas de Gran Canaria, Spain, 35020
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Oviedo, Spain, 33011
    • Research Site
  • Santander, Spain, 39008
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
  • Sevilla, Spain, 41010
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taoyuan City, Taiwan, 33305
    • Research Site
• Turkey
  • Altındağ-Ankara, Turkey, 06230
    • Research Site
  • Istanbul, Turkey, 34093
    • Research Site
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Research Site
  • Liverpool, United Kingdom, L9 7AL
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site
  • Salford, United Kingdom, M6 8HD
    • Research Site
  • West Bromwich, United Kingdom, B71 4HJ
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Research Site
  • California
    • Irvine, California, United States, 92617
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Research Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89145
      • Research Site
  • New York
    • Manhasset, New York, United States, 11030
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
    • Durham, North Carolina, United States, 27710
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Research Site
  • Texas
    • North Richland Hills, Texas, United States, 76180
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98122
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ravulizumab; Participants will receive ravulizumab in both Parts A and B.	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: Ultomiris; ALXN1210
Placebo Comparator: Placebo; Participants will receive placebo in both Parts A and B.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS-TIS) (TIS40) Response at Week 26 of the Randomized Controlled Period	Data are presented for the number of participants with a TIS40 response, defined as an IMACS-TIS score ≥ 40 at Week 26. IMACS-TIS is a clinical instrument that encompasses 6 core set measure (CSMs) (physician, patient, extra-muscular global activity, muscle strength, Health Assessment Questionnaire [HAQ], and muscle enzyme levels). A Total Improvement Score (TIS: 0-100), was determined by summing scores in each CSM, and was based on the improvement and relative weight of each CSM. A higher score indicated greater improvement. TIS40 was considered a moderate improvement score.	Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TIS at Week 26	TIS scores ranged from 0-100 with higher scores indicating a greater improvement. Scores were determined by summing scores in each of the 6 CSMs of the IMAC (physician, patient, extra-muscular global activity, muscle strength, HAQ, and muscle enzyme levels). Clinically meaningful thresholds for improvement were defined as ≥ 20 point improvement response on IMACS-TIS (TIS20; mild), ≥ 40 point improvement response on IMACS TIS (TIS40; moderate) and ≥ 60 point improvement response on IMACS-TIS (TIS60; severe). Scores were based on the improvement and relative weight of each CSM. Data are presented for TIS (least squares mean) at Week 26.	Week 26
Change From Baseline In Cutaneous Dermatomyositis Disease Area And Severity Index (CDASI) Activity Score at Week 26	The CDASI is an instrument that separately measures activity and damage in the skin of dermatomyositis (DM) participants. It contains 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis). CDASI score is calculated by rating the severity of skin disease in 15 anatomical locations on the body based on the activity and damage components. CDASI was completed by the Clinician or Clinician-Investigator while examining the participant. Total CDASI scores ranged from 0-100, with higher scores indicating a greater disease severity. Change from baseline in CDASI Total Activity Score at Week 26 was analyzed using a mixed model repeated measures (MMRM). The MMRM model included the observed Total Activity Score values at post baseline visits (Week 26) as the dependent variable.	Baseline, Week 26
Number of Participants With Response Related to Muscle Enzymes: Normalization of Most Abnormal Baseline Enzyme at Week 26	Laboratory tests were conducted to measure serum activities of muscle associated enzymes including creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and aldolase. Data are presented for the number of participants who had an abnormal muscle enzyme at baseline that had been normalized at Week 26.	Baseline, Week 26
Change From Baseline In IMACS CSMs: Extra-Muscular Disease Activity Based on Myositis Disease Activity Assessment Tool (MDAAT) at Week 26	The MDAAT assesses disease activity of extra-muscular organ systems and muscles in participants with DM. The validated MDAAT tool measures the degree of disease activity of extra-muscular organ systems and muscle on a 0-10 centimeter (cm) visual analog scale (VAS). Extra-muscular activity ranged between 0 and 10, where, 0 cm = absent and 10 cm = maximum disease activity.	Baseline, Week 26
Change From Baseline In IMACS CSMs: Physician Global Activity Assessment at Week 26	The physician global activity assessment provides an overall rating of disease activity related to myositis. Disease activity is judged by the physician based on all information available at the time of evaluation, including the participant's appearance, medical history, physical examination, laboratory testing, and prescribed medical therapy. The global disease activity score is recorded on a 10-cm VAS, where 0 cm= no evidence of disease activity and 10 cm= extremely severe disease activity.	Baseline, Week 26
Change From Baseline In IMACS CSMs: Patient Global Activity Assessment at Week 26	The patient global activity assessment provides an overall rating of disease activity related to myositis from the participant's perspective. Participants were asked to consider all of the active inflammation in their own muscles, skin, joints, intestines, heart, lungs, or other parts of the body that can improve with treatment. The patient global disease activity score was recorded on a 10-cm VAS that contained a smiley face at the 0-cm anchor and a sad face at the 10 cm anchor to help participants understand the scale. Scores ranged from 0 (no evidence of disease activity) to 10 (extremely active or severe disease activity).	Baseline, Week 26
Change From Baseline In IMACS CSMs: Manual Muscle Testing Subset 8 Muscles (MMT-8) at Week 26	The purpose of the MMT-8 was to measure muscle strength as part of the physical examination. It included a subset of 8 muscle groups: neck flexors, deltoids, biceps, wrist, extensors, gluteus maximus and medius, quadriceps, and ankle dorsiflexors. Total MMT8 scores ranged from 0 (lowest strength) to 150 (highest strength).	Baseline, Week 26
Change From Baseline In IMACS CSMs: Health Assessment Questionnaire (HAQ) at Week 26	The HAQ is a brief self-report questionnaire that assesses physical function pertaining to activities of daily living in a variety of domains. The HAQ includes 20 questions relating to 8 domains of function: dressing and grooming, arising, eating, walking, hygiene, reach, grip and usual activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score is calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do), with higher values indicating higher disability.	Baseline, Week 26
Number of Participants With CDASI Response (>=7-point Improvement) at Week 26	The CDASI is an instrument that separately measures activity and damage in the skin of dermatomyositis (DM) participants. It contains 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis). CDASI score is calculated by rating the severity of skin disease in 15 anatomical locations on the body based on the activity and damage components. CDASI was completed by the Clinician or Clinician-Investigator while examining the participant. Total CDASI scores ranged from 0-100, with higher scores indicating a greater disease severity. Data are presented for the number of participants with a CDASI response. Response was defined as a >=7 point improvement in participants who did not have an intercurrent event at or prior to the relevant timepoint.	Week 26
Number of Participants With Cutaneous Dermatomyositis Activity Physician's Global Assessment (CDA-IGA) Response at Week 26	CDA-IGA is a scale that was created to measure disease severity in participants with skin disease. It is a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) with morphologic descriptors for each score. The CDA-IGA was completed by the Investigator and was used to describe the overall appearance of lesions at a given time point. Data are presented for the number of participants with a CDA-IGA response at Week 26. A response was defined as participants with clear or almost clear skin (score of 0 or 1) who did not have an intercurrent event at or before the relevant timepoint.	Week 26
Number of Participants With ≥ 20-Point Improvement Response on IMACS-TIS (TIS20) Response at Week 26	TIS20 was defined as a ≥20-point improvement response on IMACS-TIS. IMACS-TIS is a clinical instrument that encompasses 6 CSMs (physician, patient, extra-muscular global activity, muscle strength, HAQ, and muscle enzyme levels). A Total Improvement Score (TIS: 0-100), was determined by summing scores in each CSM, and was based on the improvement and relative weight of each CSM. Higher scores indicated greater improvement/response. TIS20 is considered a mild improvement score.	Week 26
Number of Participants With ≥ 60-Point Improvement Response on IMACS-TIS (TIS60) Response at Week 26	TIS60 was defined as a ≥60-point improvement response on IMACS-TIS. IMACS-TIS is a clinical instrument that encompasses 6 CSMs (physician, patient, extra-muscular global activity, muscle strength, HAQ, and muscle enzyme levels). A Total Improvement Score (TIS: 0-100), was determined by summing scores in each CSM, and was based on the improvement and relative weight of each CSM. Higher scores indicated greater improvement/response. TIS60 is considered a severe improvement score.	Week 26
Time to First Response of TIS20, TIS40, or TIS60	TIS20, 40 and 60 were defined as a ≥20, ≥40 and ≥60-point improvement response on IMACS-TIS respectively. IMACS-TIS is a clinical instrument that encompasses 6 CSMs (physician, patient, and extra-muscular global activity, muscle strength, HAQ, and muscle enzyme levels). A Total Improvement Score (TIS: 0-100), was determined by summing scores in each CSM, and was based on the improvement and relative weight of each CSM. Higher scores indicated greater improvement/response. TIS20, 40 and 60 were considered mild, moderate and severe improvement scores respectively. Data are presented for the time to first response of TIS20, TIS40, or TIS60. The median time to TIS20, TIS40, and TIS60 was defined at the time in which 50% of the participants experienced TIS20, TIS40, or TIS60, respectively, based on a Kaplan-Meier analysis.	Baseline through Week 26
Number of Participants With Clinical Worsening (CW) During the RCP At 2 Consecutive Visits	CW was defined as one of the following: Physician's global activity VAS worsening ≥ 2 cm and MMT-8 worsening ≥ 20% compared to baseline; Global extra muscular activity worsening ≥ 2 cm on the MDAAT VAS compared to baseline; Any 3 of 5 CSMs (excluding muscle enzymes) worsening by ≥ 30% compared to baseline Data are presented for the number of participants with clinical worsening during the RCP at 2 consecutive visits.	Baseline through Week 26
Number of Participants Who Received Acute Rescue Therapy With Standard DM Treatment	Acute rescue therapy with standard DM treatment included an increased dose of a medication that was being taken for DM or the initiation of a new DM treatment (glucocorticoid and/or immunosuppressive/immunomodulatory therapy [ISTs]). Data are presented for the number of participants who received acute rescue therapy with standard DM treatment.	Baseline through Week 26

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2021
• Primary Completion (Actual): October 26, 2023
• Study Completion (Actual): May 8, 2024

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 4, 2021
• First Posted (Actual): August 10, 2021

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: July 7, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Efficacy; Pharmacokinetics; Pharmacodynamics; Ravulizumab; DM; ALXN1210; Ultomiris
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Connective Tissue Diseases; Skin Diseases; Myositis; Polymyositis; Dermatomyositis; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; Ravulizumab
• Other Study ID Numbers: ALXN1210-DM-310; 2021-001200-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No