A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multicenter Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Ravulizumab in Patients With Amyotrophic Lateral Sclerosis (ALS)
Overview
- Phase
- Phase 3
- Intervention
- Ravulizumab
- Conditions
- Amyotrophic Lateral Sclerosis
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Enrollment
- 382
- Locations
- 95
- Primary Endpoint
- Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of the study is to assess the efficacy and safety of ravulizumab for the treatment of adult participants with ALS.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A diagnosis of sporadic or familial ALS, defined by the El Escorial criteria (possible, laboratory-supported probable, probable, or definite ALS).
- •ALS onset ≤ 36 months from Screening.
- •Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
- •Upright slow vital capacity ≥ 65% predicted at Screening.
- •If on riluzole, participant must be on a stable dose for 30 days; if on edaravone, participant must be on a stable dose for 60 days (2 cycles).
- •Body weight ≥ 40 kilograms at Screening.
- •Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion Criteria
- •History of Neisseria meningitidis infection.
- •Human immunodeficiency virus (HIV) infection (evidenced by HIV 1 or HIV 2 antibody titer).
- •Dependence on invasive or non-invasive mechanical ventilation.
- •Previously or currently treated with a complement inhibitor.
- •Exposure to an investigational drug or device within 30 days of Screening or 5 half lives of the study drug, whichever is greater.
Arms & Interventions
Ravulizumab
Participants will receive ravulizumab for the duration of the study.
Intervention: Ravulizumab
Placebo
Participants will receive placebo during the 50-week Randomized Controlled Period of the study, after which they will enter the Open-label Extension Period of the study and switch to receive ravulizumab.
Intervention: Placebo
Placebo
Participants will receive placebo during the 50-week Randomized Controlled Period of the study, after which they will enter the Open-label Extension Period of the study and switch to receive ravulizumab.
Intervention: Ravulizumab
Outcomes
Primary Outcomes
Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score
Time Frame: Baseline, Week 50
The ALSFRS-Revised is a validated instrument for evaluating the levels of the functional status of participants with amyotrophic lateral sclerosis (ALS) in 4 areas, including bulbar, gross motor activity, fine motor activity, and respiratory functions. The scale included 12 functional items and each item is rated on a 0 to 4 scale, with a maximum total score of 48. A higher score indicated greater retention of function. Baseline was defined as last non-missing value on or before first study drug administration.
Secondary Outcomes
- Time To Ventilator Assistance-free Survival(Up to Week 50)
- Change From Baseline In Percent Predicted Slow Vital Capacity(Baseline, Week 50)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events, and TEAEs Leading To Study Drug Discontinuation(Baseline up to Week 156)
- Change From Baseline In Muscle Strength As Assessed By Handheld Dynamometry(Baseline, Week 50)
- Change From Baseline In Serum Neurofilament Light Chain(Baseline, Week 50)
- Change From Baseline in Serum Ravulizumab Concentration Over the Study Duration(Baseline, Predose at Week 50)
- Change From Baseline in Serum Free Complement Component 5 (C5) Concentration Over the Study Duration(Baseline, Predose at Week 50)
- Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1210(Week 50)