Clinical trial NCT04248465: An Efficacy and Safety Study of Ravulizumab in ALS Participants
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
ALS
Keywords: Ravulizumab
ALXN1210
Ultomiris
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
ALS
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-30
Enrollment: 382
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score
timeFrame: Baseline, Week 50
Secondary outcomes:
measure: Time To Ventilator Assistance-free Survival
timeFrame: Up to Week 50
measure: Change From Baseline In Percent Predicted Slow Vital Capacity
timeFrame: Baseline, Week 50
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events, and TEAEs Leading To Study Drug Discontinuation
timeFrame: Baseline up to Week 156
measure: Change From Baseline In Muscle Strength As Assessed By Handheld Dynamometry
timeFrame: Baseline, Week 50
measure: Change From Baseline In Serum Neurofilament Light Chain
timeFrame: Baseline, Week 50
measure: Change From Baseline in Serum Ravulizumab Concentration Over the Study Duration
timeFrame: Baseline, Predose at Week 50
measure: Change From Baseline in Serum Free Complement Component 5 (C5) Concentration Over the Study Duration
timeFrame: Baseline, Predose at Week 50
measure: Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1210
timeFrame: Week 50
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Phoenix
country: United States
facility: Neuromuscular Research Center and Clinic
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Orange
country: United States
facility: University of California-Irvine
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: San Francisco
country: United States
facility: Norris MDA/ALS Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus School of Medicine
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida at Shands Jacksonville
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University School Of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Las Vegas
country: United States
facility: Las Vegas Clinic
state: Nevada
city: New York
country: United States
facility: Beth Israel Medical Center - PRIME
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Charlotte
country: United States
facility: Atrium Health Neuroscience Institute
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Neurological Associates
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute-Movement Disorders Clinic
state: Texas
city: Houston
country: United States
facility: Nerve & Muscle Center of Texas
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University, Neurology Clinical and Translational Research Office
state: Virginia
city: Virginia Beach
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Camperdown
country: Australia
facility: Brain and Mind Centre
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Nedlands
country: Australia
facility: Perron Institute for Neurological and Translational Science
state: Western Australia
city: Leuven
country: Belgium
facility: UZ Leuven
city: Edmonton
country: Canada
facility: Heritage Medical Research Centre (HMRC)
state: Alberta
city: Fredericton
country: Canada
facility: Stan Cassidy Center for Rehabilitation
state: New Brunswick
city: London
country: Canada
facility: LHSC - University Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Québec
country: Canada
facility: University Hospital of Quebec-Universite Laval
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Aalborg
country: Denmark
facility: Ålborg Universitets Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital Department of Neurology
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Nice Cedex 1
country: France
facility: CHU de Nice Hôpital Pasteur 2
state: Alpes Maritimes
city: Limoges cedex
country: France
facility: CHU de Limoges - Hôpital Dupuytren
state: Haute Vienne
city: Montpellier
country: France
facility: Hopital Gui de Chauliac
state: Herault
city: Tours Cedex 9
country: France
facility: CHU Tours - Hôpital Bretonneau
state: Indre Et Loire
city: Bron cedex
country: France
facility: Hopital Neurologique Pierre Wertheimer
state: Rhone
city: Lille
country: France
facility: Hopital Roger Salengro - CHU Lille
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris cedex 13
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden Wuerttemberg
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen
state: Bayern
city: Goettigen
country: Germany
facility: Universitaetsmedizin Goettingen
state: Niedersachsen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
state: Thueringen
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Haifa
country: Israel
facility: Rambam Health Care Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: ICS Maugeri IRCCS
city: Milano
country: Italy
facility: Istituto Auxologico Italiano
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena - Ospedale Civile di Baggiovara
city: Palermo
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Torino
country: Italy
facility: University of Turin
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital
state: Aichi-Ken
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
state: Chiba-Ken
city: Ichikawa-shi
country: Japan
facility: Yoshino Neurology Clinic
state: Chiba-Ken
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi-Ken
city: Niigata-shi
country: Japan
facility: Niigata University Medical & Dental Hospital
state: Niigata-Ken
city: Ōtsu
country: Japan
facility: Shiga University of Medical Science Hospital
state: Shiga-Ken
city: Tokushima-shi
country: Japan
facility: Tokushima University Hospital
state: Tokushima-Ken
city: Bunkyo-ku
country: Japan
facility: Medical Hospital, Tokyo Medical and Dental University
state: Tokyo-To
city: Ota-ku
country: Japan
facility: Toho University Omori Medical Center
state: Tokyo-To
city: Shinjuku-Ku
country: Japan
facility: Keio University Hospital
state: Tokyo-To
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Warszawa
country: Poland
facility: CityClinic
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital San Rafael
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Huddinge
country: Sweden
facility: Karolinska Trial Alliance (KTA)
city: Umeå
country: Sweden
facility: Norrlands universitetssjukhus
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: London
country: United Kingdom
facility: The National Hospital for Neurology & Neurosurgery
state: Greater London
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: West Midlands
Study officials:
References: