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)

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

Study Overview

• Status: Terminated
• Conditions: Amyotrophic Lateral Sclerosis; ALS
• Intervention / Treatment: Biological: Ravulizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 382
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Brain and Mind Centre
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Perron Institute for Neurological and Translational Science
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2S2
      • Heritage Medical Research Centre (HMRC)
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 0C7
      • Stan Cassidy Center for Rehabilitation
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • LHSC - University Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
    • Québec, Quebec, Canada, G1J 1Z4
      • University Hospital of Quebec-Universite Laval
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0M7
      • Royal University Hospital
• Denmark
  • Aalborg, Denmark, 9100
    • Ålborg Universitets Hospital
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital Department of Neurology
  • Copenhagen, Denmark, 2400
    • Bispebjerg Hospital
• France
  • Lille, France, 59037
    • Hopital Roger Salengro - CHU Lille
  • Marseille, France, 13385
    • Hopital De La Timone
  • Paris cedex 13, France, 75651
    • Groupe Hospitalier Pitie-Salpetriere
  • Alpes Maritimes
    • Nice Cedex 1, Alpes Maritimes, France, 06001
      • CHU de Nice Hôpital Pasteur 2
  • Haute Vienne
    • Limoges cedex, Haute Vienne, France, 87042
      • CHU de Limoges - Hôpital Dupuytren
  • Herault
    • Montpellier, Herault, France, 34295
      • Hopital Gui de Chauliac
  • Indre Et Loire
    • Tours Cedex 9, Indre Et Loire, France, 37044
      • CHU Tours - Hopital Bretonneau
  • Rhone
    • Bron cedex, Rhone, France, 69677
      • Hôpital Neurologique Pierre Wertheimer
• Germany
  • Baden Wuerttemberg
    • Ulm, Baden Wuerttemberg, Germany, 89081
      • Universitaetsklinikum Ulm
  • Bayern
    • Muenchen, Bayern, Germany, 81675
      • Klinikum rechts der Isar der TU Muenchen
  • Niedersachsen
    • Goettigen, Niedersachsen, Germany, 37099
      • Universitaetsmedizin Goettingen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover
  • Thueringen
    • Jena, Thueringen, Germany, 07749
      • Universitaetsklinikum Jena
• Ireland
  • Dublin, Ireland, Dublin 9
    • Beaumont Hospital
• Israel
  • Haifa, Israel, 91096
    • Rambam Health Care Center
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital - Ein Kerem
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20149
    • Istituto Auxologico Italiano
  • Milano, Italy, 20138
    • ICS Maugeri IRCCS
  • Modena, Italy, 1355 - 41126
    • Azienda Ospedaliero-Universitaria di Modena - Ospedale civile di Baggiovara
  • Palermo, Italy, 90127
    • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Torino, Italy, 10126
    • University of Turin
• Japan
  • Aichi-Ken
    • Nagoya-shi, Aichi-Ken, Japan, 466-8560
      • Nagoya University Hospital
  • Chiba-Ken
    • Chiba-shi, Chiba-Ken, Japan, 260-8677
      • Chiba University Hospital
    • Ichikawa-shi, Chiba-Ken, Japan, 272-0827
      • Yoshino Neurology Clinic
  • Miyagi-Ken
    • Sendai-shi, Miyagi-Ken, Japan, 980-8574
      • Tohoku University Hospital
  • Niigata-Ken
    • Niigata-shi, Niigata-Ken, Japan, 951-8520
      • Niigata University Medical & Dental Hospital
  • Shiga-Ken
    • Ōtsu, Shiga-Ken, Japan, 520-2192
      • Shiga University of Medical Science Hospital
  • Tokushima-Ken
    • Tokushima-shi, Tokushima-Ken, Japan, 770-8503
      • Tokushima University Hospital
  • Tokyo-To
    • Bunkyo-ku, Tokyo-To, Japan, 113-8519
      • Medical Hospital, Tokyo Medical and Dental University
    • Ota-ku, Tokyo-To, Japan, 143-8541
      • Toho University Omori Medical Center
    • Shinjuku-Ku, Tokyo-To, Japan, 160-8582
      • Keio University Hospital
• Netherlands
  • Utrecht, Netherlands, 3508 GA
    • University Medical Centre Utrecht
• Poland
  • Warszawa, Poland, 02-473
    • CityClinic
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28016
    • Hospital San Rafael
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Barcelona
    • L'Hospitalet De Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
• Sweden
  • Huddinge, Sweden, 141 86
    • Karolinska Trial Alliance (KTA)
  • Umeå, Sweden, 90185
    • Norrlands Universitetssjukhus
• Switzerland
  • Saint Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3BG
      • The National Hospital for Neurology & Neurosurgery
  • West Midlands
    • Sheffield, West Midlands, United Kingdom, S10 2JF
      • Royal Hallamshire Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Phoenix, Arizona, United States, 85028
      • Neuromuscular Research Center and Clinic
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Research Institute
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Orange, California, United States, 92868
      • University of California-Irvine
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • San Diego, California, United States, 92093-0949
      • University of California San Diego Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center
    • San Francisco, California, United States, 94115
      • Norris MDA/ALS Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida at Shands Jacksonville
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute, Inc.
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89145
      • Las Vegas Clinic
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
    • New York, New York, United States, 10003
      • Beth Israel Medical Center - PRIME
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Atrium Health Neuroscience Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43221
      • The Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Neurological Associates
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Neuromuscular Center
    • Houston, Texas, United States, 77030
      • Nerve & Muscle Center of Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute-Movement Disorders Clinic
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University, Neurology Clinical and Translational Research Office
    • Virginia Beach, Virginia, United States, 23456
      • Sentara Neurology Specialists
  • Washington
    • Seattle, Washington, United States, 98122-4470
      • Swedish Neuroscience Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. A diagnosis of sporadic or familial ALS, defined by the El Escorial criteria (possible, laboratory-supported probable, probable, or definite ALS).
2. ALS onset ≤ 36 months from Screening.
3. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
4. Upright slow vital capacity ≥ 65% predicted at Screening.
5. 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).
6. Body weight ≥ 40 kilograms at Screening.
7. 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:

1. History of Neisseria meningitidis infection.
2. Human immunodeficiency virus (HIV) infection (evidenced by HIV 1 or HIV 2 antibody titer).
3. Dependence on invasive or non-invasive mechanical ventilation.
4. Previously or currently treated with a complement inhibitor.
5. Exposure to an investigational drug or device within 30 days of Screening or 5 half lives of the study drug, whichever is greater.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ravulizumab; Participants will receive ravulizumab for the duration of the study.	Biological: Ravulizumab; Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.; Other Names: Ultomiris; ALXN1210
Placebo Comparator: 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.	Biological: Ravulizumab; Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.; Other Names: Ultomiris; ALXN1210; Drug: Placebo; Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline In Serum Neurofilament Light Chain		Baseline, Week 50
Time To Ventilator Assistance-free Survival	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.	Up to Week 50
Change From Baseline In Percent Predicted Slow Vital Capacity	Slow vital capacity measures slow and gradual expulsion of air from the lungs using a spirometer.	Baseline, Week 50
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events, and TEAEs Leading To Study Drug Discontinuation	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.	Baseline up to Week 156
Change From Baseline In Muscle Strength As Assessed By Handheld Dynamometry	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.	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	Blood samples were collected to evaluate antibody response through development of ADAs.	Week 50

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2020
• Primary Completion (Actual): October 17, 2021
• Study Completion (Actual): October 17, 2021

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; Motor Neuron Disease; Ravulizumab; ALXN1210; Ultomiris
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Ravulizumab
• Other Study ID Numbers: ALXN1210-ALS-308; 2019-004619-30 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No