Clinical trial NCT04999020: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Dermatomyositis
Keywords: Ravulizumab
ALXN1210
Ultomiris
Pharmacokinetics
Pharmacodynamics
Efficacy
DM
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-10
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: 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
timeFrame: Week 26
Secondary outcomes:
measure: TIS at Week 26
timeFrame: Week 26
measure: Change From Baseline In Cutaneous Dermatomyositis Disease Area And Severity Index (CDASI) Activity Score at Week 26
timeFrame: Baseline, Week 26
measure: Number of Participants With Response Related to Muscle Enzymes: Normalization of Most Abnormal Baseline Enzyme at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline In IMACS CSMs: Extra-Muscular Disease Activity Based on Myositis Disease Activity Assessment Tool (MDAAT) at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline In IMACS CSMs: Physician Global Activity Assessment at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline In IMACS CSMs: Patient Global Activity Assessment at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline In IMACS CSMs: Manual Muscle Testing Subset 8 Muscles (MMT-8) at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline In IMACS CSMs: Health Assessment Questionnaire (HAQ) at Week 26
timeFrame: Baseline, Week 26
measure: Number of Participants With CDASI Response (>=7-point Improvement) at Week 26
timeFrame: Week 26
measure: Number of Participants With Cutaneous Dermatomyositis Activity Physician's Global Assessment (CDA-IGA) Response at Week 26
timeFrame: Week 26
measure: Number of Participants With ≥ 20-Point Improvement Response on IMACS-TIS (TIS20) Response at Week 26
timeFrame: Week 26
measure: Number of Participants With ≥ 60-Point Improvement Response on IMACS-TIS (TIS60) Response at Week 26
timeFrame: Week 26
measure: Time to First Response of TIS20, TIS40, or TIS60
timeFrame: Baseline through Week 26
measure: Number of Participants With Clinical Worsening (CW) During the RCP At 2 Consecutive Visits
timeFrame: Baseline through Week 26
measure: Number of Participants Who Received Acute Rescue Therapy With Standard DM Treatment
timeFrame: Baseline through Week 26
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Fairway
country: United States
facility: Research Site
state: Kansas
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Paris
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Freiburg im Breisgau
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Jung-gu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Bilbao (Vizcaya)
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
Study officials:
References: