A Phase 2/3 Randomised Study of Ravulizumab in Adults with Dermatomyositis
Research type
Research Study
Full 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.
IRAS ID
1003864
Contact name
U. Shivraj Sohur, M.D., Ph.D.
Contact email
Sponsor organisation
Alexion Pharmaceuticals, Inc.
Eudract number
2021-001200-15
Clinicaltrials.gov Identifier
Research summary
Summary of Research
Dermatomyositis (DM) is a condition that may cause distinct skin rashes and muscle weakness which can make everyday tasks difficult. The purpose of this double-blind study is to determine whether treatment with ravulizumab (which blocks the complement activity) is effective in treating adult patients with DM.There are currently limited treatment options available for patients with DM so there is still a high unmet need for safe and effective treatment options for this disease.
This study will comprise 2 parts:
Part A (Phase 2): Participants in Part A who meet all eligibility criteria will be randomised in a 2:1 ratio to ravulizumab or placebo, via an intravenous (IV) infusion on 4 separate occasions, for approximately 6 months.
Part B (Phase 3): this part will only open after Part A is complete. Participants in Part B who meet all eligibility criteria will be randomised in a 1:1 ratio to ravulizumab or placebo, via IV infusion on 7 separate occasions, for approximately 11.5 months.
Participants from Part A will not participate in Part B and vice versa.
An open label extension (OLE) lasting up to 1.5 years will be available for all eligible participants from Part A and Part B. All participants will receive ravulizumab via an IV infusion on 10 separate occasions.
Assessments include physical examinations, vital signs, ECG, blood and urine sample collection for testing, skin rash photos and completion of quality of life questionnaires A vaccination against meningitis infection and/or antibiotics to protect against meningitis will be given. The total study duration will be about 2 years for Part A and about 2.5 years for Part B.
For Part A, about 40 study sites and for Part B, about 100 sites will be opened around the world to enrol 48 and 132 patients, respectively.
Summary of Results
The researchers wanted to see if ravulizumab was more effective than placebo in the treatment of participants with dermatomyositis after 26 weeks. To answer this question, they evaluated the participants’ overall improvement of symptoms using a tool called TIS40. TIS40 measures how effective a treatment is by assessing the severity of symptoms and providing an overall score. Researchers considered symptoms to be improved if participants achieved a TIS40 score of 40 or higher, and compared the percentage of participants showing symptom improvement between the ravulizumab and placebo groups.
Overall, 9 out of 26 participants (34.6%) in the ravulizumab group and 6 out of 12 participants (50%) in the placebo group achieved a TIS40 score of at least 40. These results show that ravulizumab did not improve symptoms in participants with dermatomyositis when compared to placebo.What were the safety findings in this study?
A side effect is any symptom a participant has during the study which may or may not be related to the study treatment. Related side effects are unwanted medical events that happen during the study and are considered to be related to study treatment. Side effects are classified as either “mild,” “moderate,” or “severe” in intensity.
A serious side effect is thought to be a significant medical event (e.g., requires a person to be admitted to the hospital, is life-threatening, causes disability, or causes death).
Side effects can vary from person to person. Researchers keep a record of all the side effects participants have when new treatments are studied. This helps determine which side effects occur as a result of the study treatment and which occur by chance or because of the participant’s underlying disease.What serious side effects did participants have in this study?
Overall, 2 out of 38 participants (5.3%) had serious side effects during the Treatment Period. Both participants were in the ravulizumab group and none of the side effects were thought by study doctors to be related to ravulizumab.
Overall, 8 out of 31 participants (25.8%) had serious side effects while receiving ravulizumab during the Extended Treatment Period. The majority of side effects were thought by study doctors to be not related to ravulizumab. One participant had a COVID-19 infection, which was thought to be related to ravulizumab. Patients receiving ravulizumab may be more likely to catch infections, including COVID-19.
No participants died during the study.What side effects did participants have in this study?
Overall, 32 out of 38 participants (84.2%) had side effects during the Treatment Period. Of these, 22 out of 25 (88%) were in the ravulizumab group and 10 out of 13 (76.9%) were in the placebo group. The majority of side effects were thought by study doctors to be not related to ravulizumab or placebo. A total of 6 out of 25 participants (24%) had a side effect that was thought by the study doctors to be related to ravulizumab; a total of 3 out of 13 (23.1%) had a side effect that was thought by the study doctors to be related to placebo. Each of the related side effects happened in only one participant.
Overall, 24 out of 31 participants (77.4%) had side effects while receiving ravulizumab during the Extended Treatment Period. The majority of side effects were thought by study doctors to be not related to ravulizumab. A total of 6 out of 31 participants (19.4%) had a side effect that was thought by the study doctors to be related to ravulizumab. Each of these related side effects happened in only one participant.
Overall, 24 out of 31 participants (77.4%) had side effects while receiving ravulizumab during the Extended Treatment Period. The majority of side effects were thought by study doctors to be not related to ravulizumab. A total of 6 out of 31 participants (19.4%) had a side effect that was thought by the study doctors to be related to ravulizumab. Each of these related side effects happened in only one participant.
Were there any other important safety findings in this study?
Overall, 2 out of 38 participants (5.3%) stopped taking ravulizumab because of side effects during the Treatment Period. These side effects included mycobacterial infection (an infection caused by a type of bacteria called mycobacteria), which was thought by study doctors to be related to ravulizumab.
Overall, 2 out of 31 participants (6.5%) stopped taking ravulizumab because of side effects during the Extended Treatment Period. The side effects were not considered to be related to ravulizumab.
No participants had meningococcal infections.REC name
East of Scotland Research Ethics Service REC 2
REC reference
21/ES/0068
Date of REC Opinion
24 Aug 2021
REC opinion
Further Information Favourable Opinion