An Efficacy and Safety Study of Ravulizumab in ALS Participants

Phase 3

Terminated

Conditions: Amyotrophic Lateral Sclerosis
ALS

Interventions: Biological: Ravulizumab
Drug: Placebo

Registration Number: NCT04248465

Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary: The purpose of the study is to assess the efficacy and safety of ravulizumab for the treatment of adult participants with ALS.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 382

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ravulizumab	Ravulizumab	Participants will receive ravulizumab for the duration of the study.
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.
Placebo	Ravulizumab	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score	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 Outcome Measures

Name	Time	Method
Time To Ventilator Assistance-free Survival	Up to Week 50	Ventilation Assistance-Free Survival (VAFS) is a composite endpoint of survival and severe and irreversible respiratory decline. The use of VAFS allowed for the collection of survival data that was not impacted by survival prolongation from noninvasive or permanent ventilatory interventions which could prolong life without impacting underlying disease progression.
Change From Baseline In Percent Predicted Slow Vital Capacity	Baseline, Week 50	Slow vital capacity measures slow and gradual expulsion of air from the lungs using a spirometer.
Change From Baseline In Serum Neurofilament Light Chain	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	An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as AEs that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Change From Baseline In Muscle Strength As Assessed By Handheld Dynamometry	Baseline, Week 50	Handheld dynamometry (HHD) is a procedure for quantitative strength testing. Muscle strength testing was performed on prespecified muscles in the upper and lower extremities bilaterally and the force measurements were recorded. Force of measurement is reported in megascores (lower, upper, total). The total megascore is defined as the average of the non-missing ratios over baseline for all the muscles involved. The megascore at baseline is always 100. The range of a potential megascore can not be determined in advance. A megascore \>100 indicates more strength compared to baseline.
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	Blood samples were collected to evaluate antibody response through development of ADAs.

Trial Locations

Locations (95): University Hospital of Quebec-Universite Laval
🇨🇦
Québec, Quebec, Canada
Royal University Hospital
🇨🇦
Saskatoon, Saskatchewan, Canada
Beaumont Hospital
🇮🇪
Dublin, Ireland
Hadassah University Hospital - Ein Kerem
🇮🇱
Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱
Tel Aviv, Israel
Tohoku University Hospital
🇯🇵
Sendai-shi, Miyagi-Ken, Japan
Niigata University Medical & Dental Hospital
🇯🇵
Niigata-shi, Niigata-Ken, Japan
Tokushima University Hospital
🇯🇵
Tokushima-shi, Tokushima-Ken, Japan
Shiga University of Medical Science Hospital
🇯🇵
Ōtsu, Shiga-Ken, Japan
Medical Hospital, Tokyo Medical and Dental University
🇯🇵
Bunkyo-ku, Tokyo-To, Japan
Keio University Hospital
🇯🇵
Shinjuku-Ku, Tokyo-To, Japan
University Medical Centre Utrecht
🇳🇱
Utrecht, Netherlands
CityClinic
🇵🇱
Warszawa, Poland
Kantonsspital St. Gallen
🇨🇭
Saint Gallen, Switzerland
Johns Hopkins University School Of Medicine
🇺🇸
Baltimore, Maryland, United States
Brain and Mind Centre
🇦🇺
Camperdown, New South Wales, Australia
Las Vegas Clinic
🇺🇸
Las Vegas, Nevada, United States
Houston Methodist Neurological Institute-Movement Disorders Clinic
🇺🇸
Houston, Texas, United States
Nerve & Muscle Center of Texas
🇺🇸
Houston, Texas, United States
Sentara Neurology Specialists
🇺🇸
Virginia Beach, Virginia, United States
The Ohio State University
🇺🇸
Columbus, Ohio, United States
Swedish Neuroscience Institute
🇺🇸
Seattle, Washington, United States
University of California San Diego Medical Center
🇺🇸
San Diego, California, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
University of Kansas Medical Center Research Institute, Inc.
🇺🇸
Kansas City, Kansas, United States
Norris MDA/ALS Center
🇺🇸
San Francisco, California, United States
University of South Florida
🇺🇸
Tampa, Florida, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
Royal Brisbane and Women's Hospital
🇦🇺
Herston, Queensland, Australia
University of Colorado Anschutz Medical Campus School of Medicine
🇺🇸
Aurora, Colorado, United States
HonorHealth Research Institute
🇺🇸
Scottsdale, Arizona, United States
University of Florida at Shands Jacksonville
🇺🇸
Jacksonville, Florida, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
Barrow Neurological Institute
🇺🇸
Phoenix, Arizona, United States
University of California-Irvine
🇺🇸
Orange, California, United States
Neuromuscular Research Center and Clinic
🇺🇸
Phoenix, Arizona, United States
University of Southern California
🇺🇸
Los Angeles, California, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Allegheny Neurological Associates
🇺🇸
Pittsburgh, Pennsylvania, United States
Beth Israel Medical Center - PRIME
🇺🇸
New York, New York, United States
Stanford University Medical Center
🇺🇸
Palo Alto, California, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
Austin Neuromuscular Center
🇺🇸
Austin, Texas, United States
Universitaetsmedizin Goettingen
🇩🇪
Goettigen, Niedersachsen, Germany
Westmead Hospital
🇦🇺
Westmead, New South Wales, Australia
Heritage Medical Research Centre (HMRC)
🇨🇦
Edmonton, Alberta, Canada
UZ Leuven
🇧🇪
Leuven, Belgium
Perron Institute for Neurological and Translational Science
🇦🇺
Nedlands, Western Australia, Australia
Ålborg Universitets Hospital
🇩🇰
Aalborg, Denmark
Toronto Sunnybrook Hospital
🇨🇦
Toronto, Ontario, Canada
LHSC - University Hospital
🇨🇦
London, Ontario, Canada
Ospedale San Raffaele
🇮🇹
Milano, Italy
Hospital San Rafael
🇪🇸
Madrid, Spain
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
🇮🇹
Palermo, Italy
Karolinska Trial Alliance (KTA)
🇸🇪
Huddinge, Sweden
Rambam Health Care Center
🇮🇱
Haifa, Israel
Istituto Auxologico Italiano
🇮🇹
Milano, Italy
Stan Cassidy Center for Rehabilitation
🇨🇦
Fredericton, New Brunswick, Canada
Azienda Ospedaliero-Universitaria di Modena - Ospedale Civile di Baggiovara
🇮🇹
Modena, Italy
Norrlands universitetssjukhus
🇸🇪
Umeå, Sweden
The National Hospital for Neurology & Neurosurgery
🇬🇧
London, Greater London, United Kingdom
Universitaetsklinikum Ulm
🇩🇪
Ulm, Baden Wuerttemberg, Germany
Medizinische Hochschule Hannover
🇩🇪
Hannover, Niedersachsen, Germany
Hopital Neurologique Pierre Wertheimer
🇫🇷
Bron cedex, Rhone, France
Groupe Hospitalier Pitie-Salpetriere
🇫🇷
Paris cedex 13, France
Azienda Ospedaliero Universitaria Pisana
🇮🇹
Pisa, Italy
CHU de Limoges - Hôpital Dupuytren
🇫🇷
Limoges cedex, Haute Vienne, France
Hopital Gui de Chauliac
🇫🇷
Montpellier, Herault, France
Hopital Roger Salengro - CHU Lille
🇫🇷
Lille, France
Hôpital de la Timone
🇫🇷
Marseille, France
ICS Maugeri IRCCS
🇮🇹
Milano, Italy
Chiba University Hospital
🇯🇵
Chiba-shi, Chiba-Ken, Japan
Yoshino Neurology Clinic
🇯🇵
Ichikawa-shi, Chiba-Ken, Japan
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Toho University Omori Medical Center
🇯🇵
Ota-ku, Tokyo-To, Japan
Royal Hallamshire Hospital
🇬🇧
Sheffield, West Midlands, United Kingdom
Klinikum rechts der Isar der TU Muenchen
🇩🇪
Muenchen, Bayern, Germany
Universitaetsklinikum Jena
🇩🇪
Jena, Thueringen, Germany
Hospital Universitari de Bellvitge
🇪🇸
L'Hospitalet De Llobregat, Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸
Valencia, Spain
Hospital for Special Surgery
🇺🇸
New York, New York, United States
The Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Indiana University Medical Center
🇺🇸
Indianapolis, Indiana, United States
University of California San Francisco Medical Center
🇺🇸
San Francisco, California, United States
Atrium Health Neuroscience Institute
🇺🇸
Charlotte, North Carolina, United States
University of Vermont Medical Center
🇺🇸
Burlington, Vermont, United States
Virginia Commonwealth University, Neurology Clinical and Translational Research Office
🇺🇸
Richmond, Virginia, United States
Montreal Neurological Institute and Hospital
🇨🇦
Montreal, Quebec, Canada
Aarhus University Hospital Department of Neurology
🇩🇰
Aarhus, Denmark
CHU de Nice Hôpital Pasteur 2
🇫🇷
Nice Cedex 1, Alpes Maritimes, France
Bispebjerg Hospital
🇩🇰
Copenhagen, Denmark
CHU Tours - Hôpital Bretonneau
🇫🇷
Tours Cedex 9, Indre Et Loire, France
Nagoya University Hospital
🇯🇵
Nagoya-shi, Aichi-Ken, Japan
University of Turin
🇮🇹
Torino, Italy