NCT04999020

Ravulizumab Versus Placebo in Adult Participants With Dermatomyositis

Terminated Phase 2, PHASE3 Results posted Last updated 9 July 2025

What this trial tests

Phase 2, PHASE3 trial testing Ravulizumab in Dermatomyositis in 38 participants. Terminated before completion.

Timeline

19 November 2021

Primary endpoint
26 October 2023

8 May 2024

Quick facts

Lead sponsor	Alexion Pharmaceuticals, Inc.
Phase	Phase 2, PHASE3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	38
Start date	19 November 2021
Primary completion	26 October 2023
Estimated completion	8 May 2024
Sites	111 locations across France, Italy, Japan, Taiwan, United Kingdom, Germany, Poland, South Korea

Drugs / interventions tested

• Ravulizumab (RAVULIZUMAB) — full drug profile →
• Placebo

Conditions studied

• Dermatomyositis — all drugs for Dermatomyositis →

Sponsor

Alexion Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Dermatomyositis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Week 26

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.

Group	Value	95% CI
RCP: Ravulizumab	9
RCP: Placebo	6

TIS at Week 26 Secondary · 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 presente

Group	Value	95% CI
RCP: Ravulizumab	31.16	± 4.185
RCP: Placebo	43.28	± 6.650

Change From Baseline In Cutaneous Dermatomyositis Disease Area And Severity Index (CDASI) Activity Score at Week 26 Secondary · Baseline, 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 fro

Group	Value	95% CI
RCP: Ravulizumab	-3.80	± 1.249
RCP: Placebo	-7.47	± 2.021

Number of Participants With Response Related to Muscle Enzymes: Normalization of Most Abnormal Baseline Enzyme at Week 26 Secondary · Baseline, 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.

Group	Value	95% CI
RCP: Ravulizumab	4
RCP: Placebo	1

Change From Baseline In IMACS CSMs: Extra-Muscular Disease Activity Based on Myositis Disease Activity Assessment Tool (MDAAT) at Week 26 Secondary · Baseline, 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.

Group	Value	95% CI
RCP: Ravulizumab	-0.92	± 0.383
RCP: Placebo	-2.13	± 0.614

Change From Baseline In IMACS CSMs: Physician Global Activity Assessment at Week 26 Secondary · Baseline, 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.

Group	Value	95% CI
RCP: Ravulizumab	-1.18	± 0.413
RCP: Placebo	-1.97	± 0.649

Change From Baseline In IMACS CSMs: Patient Global Activity Assessment at Week 26 Secondary · Baseline, 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 a

Group	Value	95% CI
RCP: Ravulizumab	-1.43	± 0.432
RCP: Placebo	-1.12	± 0.699

Change From Baseline In IMACS CSMs: Manual Muscle Testing Subset 8 Muscles (MMT-8) at Week 26 Secondary · Baseline, 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).

Group	Value	95% CI
RCP: Ravulizumab	9.5	± 1.85
RCP: Placebo	12.6	± 2.98

Change From Baseline In IMACS CSMs: Health Assessment Questionnaire (HAQ) at Week 26 Secondary · Baseline, 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 sco

Group	Value	95% CI
RCP: Ravulizumab	-0.1289	± 0.08607
RCP: Placebo	-0.4188	± 0.13676

Number of Participants With CDASI Response (>=7-point Improvement) at Week 26 Secondary · 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

Group	Value	95% CI
RCP: Ravulizumab	6
RCP: Placebo	4

Number of Participants With Cutaneous Dermatomyositis Activity Physician's Global Assessment (CDA-IGA) Response at Week 26 Secondary · 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

Group	Value	95% CI
RCP: Ravulizumab	5
RCP: Placebo	2

Number of Participants With ≥ 20-Point Improvement Response on IMACS-TIS (TIS20) Response at Week 26 Secondary · 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.

Group	Value	95% CI
RCP: Ravulizumab	14
RCP: Placebo	9

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 130 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

RCP: Ravulizumab

Serious: 2/25 (8%)

Deaths: 0/25

RCP: Placebo

Serious: 0/13 (0%)

Deaths: 0/13

OLE: Ravulizumab to Ravulizumab

Serious: 4/22 (18%)

Deaths: 0/22

OLE: Placebo to Ravulizumab

Serious: 4/9 (44%)

Deaths: 0/9

Serious adverse events (15 terms)

Reaction	System	RCP: Ravulizumab	RCP: Placebo	OLE: Ravulizumab to Ravuli…	OLE: Placebo to Ravulizumab
Constipation	Gastrointestinal disorders	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—
Agranulocytosis	Blood and lymphatic system disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Impaired healing	General disorders	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—
Escherichia urinary tract infection	Infections and infestations	—	—	—	—
Endometrial hyperplasia	Reproductive system and breast disorders	—	—	—	—
Cutaneous calcification	Skin and subcutaneous tissue disorders	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—
Coronary artery stenosis	Cardiac disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Intestinal haemorrhage	Gastrointestinal disorders	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Hypovolaemic shock	Vascular disorders	—	—	—	—

Other adverse events (49 terms — click to expand)

Reaction	System	RCP: Ravulizumab	RCP: Placebo	OLE: Ravulizumab to Ravuli…	OLE: Placebo to Ravulizumab
Diarrhoea	Gastrointestinal disorders	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Enterocolitis	Gastrointestinal disorders	—	—	—	—
Influenza like illness	General disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Neuralgia	Nervous system disorders	—	—	—	—
Vertigo	Ear and labyrinth disorders	—	—	—	—
Cushingoid	Endocrine disorders	—	—	—	—
Diabetic retinopathy	Eye disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Anal erosion	Gastrointestinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Diverticulum intestinal	Gastrointestinal disorders	—	—	—	—
Hypoaesthesia oral	Gastrointestinal disorders	—	—	—	—
Large intestine polyp	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Tongue movement disturbance	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Vaccination site swelling	General disorders	—	—	—	—
Genital infection fungal	Infections and infestations	—	—	—	—
Influenza	Infections and infestations	—	—	—	—
Pyoderma	Infections and infestations	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Compression fracture	Injury, poisoning and procedural complications	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Osteoporosis	Musculoskeletal and connective tissue disorders	—	—	—	—
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	—	—	—	—
Taste disorder	Nervous system disorders	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—

Most-reported serious reactions: Constipation, Syncope, Agranulocytosis, Anaemia, Impaired healing, COVID-19, Escherichia urinary tract infection, Endometrial hyperplasia.

Data from ClinicalTrials.gov NCT04999020 adverse events section.

Sponsor's own description

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).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pathophysiological Mechanisms and Treatment of Dermatomyositis and Immune Mediated Necrotizing Myopathies: A Focused Review.
   Kamperman RG, van der Kooi AJ, de Visser M, Aronica E, et al · · 2022 · cited 38× · PMID 35457124 · DOI 10.3390/ijms23084301
2. Dermatomyositis: Practical Guidance and Unmet Needs.
   Cassard L, Seraly N, Riegert M, Patel A, et al · · 2024 · cited 14× · PMID 38464459 · DOI 10.2147/itt.s381472
3. Past, Present, and Future in Dermatomyositis Therapeutics.
   Chung MP, Paik JJ. · · 2022 · cited 9× · PMID 38650607 · DOI 10.1007/s40674-022-00193-6
4. Clinical pearls and promising therapies in myositis.
   Connolly CM, Paik JJ. · · 2023 · cited 8× · PMID 37158055 · DOI 10.1080/1744666x.2023.2212162
5. Anti-complement Agents for Autoimmune Neurological Disease.
   McCombe JA, Pittock SJ. · · 2022 · cited 7× · PMID 35553024 · DOI 10.1007/s13311-022-01223-w
6. How I Treat Complement-Mediated TMA.
   Sperati CJ. · · 2022 · cited 5× · PMID 35074846 · DOI 10.2215/cjn.13581021
7. Complement activation in immunological neurological disorders: mechanisms and therapeutic strategies.
   Chen JY, Sanghani N, Palmer K, Li Y, et al · · 2025 · PMID 41409222 · DOI 10.3389/fneur.2025.1695461