|Study title||A Phase-3, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multicentre Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Ravulizumab in Patients With Amyotrophic Lateral Sclerosis (ALS).|
|UK Chief Investigator||Professor Dame Pamela Shaw|
|Research summary||Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons leading to severe disability and eventually death. Currently, riluzole and edaravone are the only available medications approved for the treatment of ALS that may slow disease progression. Management of ALS is otherwise supportive, palliative, and symptom based. Given the seriousness of the disease and limitations of the available treatments, there is a substantial unmet need for developing additional treatments that are efficacious and safe for patients with ALS.
The pathogenesis of ALS is largely unknown, but immune dysregulation and neuroinflammation have been implicated as potential mediators of disease. The therapeutic rationale for complement component 5 (C5) inhibition in ALS is supported by evidence of dysregulation of the complement system in tissue from patients with ALS. Furthermore, functional and survival benefits of C5 signaling blockade have been demonstrated in animal models of ALS.
Ravulizumab (Ultomiris®) is a recombinant, humanized monoclonal antibody with high specificity for human C5. Ravulizumab has been shown to achieve immediate, complete, and sustained inhibition of terminal complement in adult patients with paroxysmal nocturnal hemoglobinuria (approved in the US, European Union, and Japan) and in pediatric and adult patients with atypical hemolytic uremic syndrome (approved in the US). It is expected that the same dosing regimen will also achieve comparable inhibition of complement-mediated damage in patients with ALS, which may slow ALS disease progression.
The primary objective of this study is to investigate the efficacy and safety of ravulizumab in adult patients with ALS.
|Inclusion/exclusion criteria||Key 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.
Key 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.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
|Current status||Closed to recruitment|
|Locations||Royal Hallamshire Hospital, Sheffield
University College London Hospitals
|Recruitment group(s)||Patients with MND|
|Recruitment target(s)||50 participants|
|Key dates||Study start date: 18 September 2020 (UKI)
Study completion date: 21 April 2021 (UK)
|Funder(s)||Alexion Pharmaceuticals Inc.|
|Sponsor||Alexion Pharmaceuticals Inc.|
|Study design||Interventional (clinical trial)|
|Intervention (if applicable)||Drug: Ravulizumab
|Phase (if applicable)||3|
|Outcome measures||Primary Outcome Measures:
- Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score (Time Frame: Baseline, Week 50)
Secondary Outcome Measures:
- Time To Ventilator Assistance-free Survival (Time Frame: Up to Week 50)
- Change From Baseline In Slow Vital Capacity (Time Frame: Baseline, Week 50)
- Incidence Of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events, And TEAEs Leading To Study Drug Discontinuation (Time Frame: Baseline through Week 156)
- Change From Baseline In Muscle Strength As Assessed By Handheld Dynamometry (Time Frame: Baseline, Week 50)
- Change From Baseline In Serum Neurofilament Light Chain (Time Frame: Baseline, Week 50)
|Publications / Results reports|
|Participant Information Sheet|