Study Stopped
The IDMC recommended the study be discontinued due to lack of efficacy with ravulizumab.
An Efficacy and Safety Study of Ravulizumab in ALS Participants
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)
2 other identifiers
interventional
382
17 countries
95
Brief Summary
The purpose of the study is to assess the efficacy and safety of ravulizumab for the treatment of adult participants with ALS.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2020
95 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 27, 2020
CompletedFirst Posted
Study publicly available on registry
January 30, 2020
CompletedStudy Start
First participant enrolled
March 30, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 17, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
October 17, 2021
CompletedResults Posted
Study results publicly available
January 10, 2023
CompletedJanuary 10, 2023
December 1, 2022
1.6 years
January 27, 2020
September 22, 2022
December 15, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score
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.
Baseline, Week 50
Secondary Outcomes (8)
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
- +3 more secondary outcomes
Study Arms (2)
Ravulizumab
EXPERIMENTALParticipants will receive ravulizumab for the duration of the study.
Placebo
PLACEBO COMPARATORParticipants 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.
Interventions
Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.
Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (95)
Barrow Neurological Institute
Phoenix, Arizona, 85013, United States
Neuromuscular Research Center and Clinic
Phoenix, Arizona, 85028, United States
HonorHealth Research Institute
Scottsdale, Arizona, 85251, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
University of Southern California
Los Angeles, California, 90033, United States
University of California-Irvine
Orange, California, 92868, United States
Stanford University Medical Center
Palo Alto, California, 94304, United States
University of California San Diego Medical Center
San Diego, California, 92093-0949, United States
Norris MDA/ALS Center
San Francisco, California, 94115, United States
University of California San Francisco Medical Center
San Francisco, California, 94143, United States
University of Colorado Anschutz Medical Campus School of Medicine
Aurora, Colorado, 80045, United States
University of Florida at Shands Jacksonville
Jacksonville, Florida, 32209, United States
University of South Florida
Tampa, Florida, 33612, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
University of Kansas Medical Center Research Institute, Inc.
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Johns Hopkins University School Of Medicine
Baltimore, Maryland, 21205, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Las Vegas Clinic
Las Vegas, Nevada, 89145, United States
Beth Israel Medical Center - PRIME
New York, New York, 10003, United States
Hospital for Special Surgery
New York, New York, 10021, United States
Atrium Health Neuroscience Institute
Charlotte, North Carolina, 28207, United States
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
The Ohio State University
Columbus, Ohio, 43221, United States
Allegheny Neurological Associates
Pittsburgh, Pennsylvania, 15212, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Austin Neuromuscular Center
Austin, Texas, 78756, United States
Houston Methodist Neurological Institute-Movement Disorders Clinic
Houston, Texas, 77030, United States
Nerve & Muscle Center of Texas
Houston, Texas, 77030, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
Virginia Commonwealth University, Neurology Clinical and Translational Research Office
Richmond, Virginia, 23298, United States
Sentara Neurology Specialists
Virginia Beach, Virginia, 23456, United States
Swedish Neuroscience Institute
Seattle, Washington, 98122-4470, United States
Brain and Mind Centre
Camperdown, New South Wales, 2050, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029, Australia
Perron Institute for Neurological and Translational Science
Nedlands, Western Australia, 6009, Australia
UZ Leuven
Leuven, 3000, Belgium
Heritage Medical Research Centre (HMRC)
Edmonton, Alberta, T6G2S2, Canada
Stan Cassidy Center for Rehabilitation
Fredericton, New Brunswick, E3B 0C7, Canada
LHSC - University Hospital
London, Ontario, N6A 5A5, Canada
Toronto Sunnybrook Hospital
Toronto, Ontario, M4N 3M5, Canada
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A 2B4, Canada
University Hospital of Quebec-Universite Laval
Québec, Quebec, G1J 1Z4, Canada
Royal University Hospital
Saskatoon, Saskatchewan, S7K 0M7, Canada
Ålborg Universitets Hospital
Aalborg, 9100, Denmark
Aarhus University Hospital Department of Neurology
Aarhus, 8200, Denmark
Bispebjerg Hospital
Copenhagen, 2400, Denmark
CHU de Nice Hôpital Pasteur 2
Nice, Alpes Maritimes, 06001, France
CHU de Limoges - Hôpital Dupuytren
Limoges, Haute Vienne, 87042, France
Hopital Gui de Chauliac
Montpellier, Herault, 34295, France
CHU Tours - Hôpital Bretonneau
Tours, Indre Et Loire, 37044, France
Hopital Neurologique Pierre Wertheimer
Bron, Rhone, 69677, France
Hopital Roger Salengro - CHU Lille
Lille, 59037, France
Hôpital de la Timone
Marseille, 13385, France
Groupe Hospitalier Pitie-Salpetriere
Paris, 75651, France
Universitaetsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081, Germany
Klinikum rechts der Isar der TU Muenchen
Munich, Bavaria, 81675, Germany
Universitaetsmedizin Goettingen
Goettigen, Lower Saxony, 37099, Germany
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625, Germany
Universitaetsklinikum Jena
Jena, Thuringia, 07749, Germany
Beaumont Hospital
Dublin, DUBLIN 9, Ireland
Rambam Health Care Center
Haifa, 91096, Israel
Hadassah University Hospital - Ein Kerem
Jerusalem, 91120, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Ospedale San Raffaele
Milan, 20132, Italy
ICS Maugeri IRCCS
Milan, 20138, Italy
Istituto Auxologico Italiano
Milan, 20149, Italy
Azienda Ospedaliero-Universitaria di Modena - Ospedale Civile di Baggiovara
Modena, 1355 - 41126, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
Palermo, 90127, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126, Italy
University of Turin
Torino, 10126, Italy
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560, Japan
Chiba University Hospital
Chiba, Chiba, 260-8677, Japan
Yoshino Neurology Clinic
Ichikawa-shi, Chiba, 272-0827, Japan
Tohoku University Hospital
Sendai, Miyagi, 980-8574, Japan
Niigata University Medical & Dental Hospital
Niigata, Niigata, 951-8520, Japan
Shiga University of Medical Science Hospital
Ōtsu, Shiga, 520-2192, Japan
Tokushima University Hospital
Tokushima, Tokushima, 770-8503, Japan
Medical Hospital, Tokyo Medical and Dental University
Bunkyō City, Tokyo-To, 113-8519, Japan
Toho University Omori Medical Center
Ōta-ku, Tokyo-To, 143-8541, Japan
Keio University Hospital
Shinjuku-Ku, Tokyo-To, 160-8582, Japan
University Medical Centre Utrecht
Utrecht, 3508 GA, Netherlands
CityClinic
Warsaw, 02-473, Poland
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital San Rafael
Madrid, 28016, Spain
Hospital Universitari i Politecnic La Fe
Valencia, 46026, Spain
Karolinska Trial Alliance (KTA)
Huddinge, 141 86, Sweden
Norrlands universitetssjukhus
Umeå, 90185, Sweden
Kantonsspital St. Gallen
Sankt Gallen, 9007, Switzerland
The National Hospital for Neurology & Neurosurgery
London, Greater London, WC1N 3BG, United Kingdom
Royal Hallamshire Hospital
Sheffield, West Midlands, S10 2JF, United Kingdom
Related Publications (1)
Genge A, van den Berg LH, Frick G, Han S, Abikoff C, Simmons A, Lin Q, Patra K, Kupperman E, Berry JD. Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2023 Oct 1;80(10):1089-1097. doi: 10.1001/jamaneurol.2023.2851.
PMID: 37695623DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The IDMC recommended the study be discontinued due to lack of efficacy with ravulizumab.
Results Point of Contact
- Title
- Alexion Pharmaceuticals Inc.
- Organization
- Alexion Pharmaceuticals Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 27, 2020
First Posted
January 30, 2020
Study Start
March 30, 2020
Primary Completion
October 17, 2021
Study Completion
October 17, 2021
Last Updated
January 10, 2023
Results First Posted
January 10, 2023
Record last verified: 2022-12