An Efficacy and Safety Study of Ravulizumab in ALS Participants

Amyotrophic Lateral Sclerosis Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04248465
• Other study ID #: ALXN1210-ALS-308
• Secondary ID: 2019-004619-30
• Status: Terminated
• Phase: Phase 3
• Start date: March 30, 2020
• Est. completion date: October 17, 2021

Study information

• Verified date: December 2022
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 382
• Est. completion date: October 17, 2021
• Est. primary completion date: October 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ALS
• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Placebo
Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.

Biological:
• Ravulizumab
Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Ireland,  Israel,  Italy,  Japan,  Netherlands,  Poland,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline In Serum Neurofilament Light Chain		Baseline, Week 50
Secondary	Change From Baseline in Serum Ravulizumab Concentration Over the Study Duration		Baseline, Predose at Week 50
Secondary	Change From Baseline in Serum Free Complement Component 5 (C5) Concentration Over the Study Duration		Baseline, Predose at Week 50
Secondary	Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1210	Blood samples were collected to evaluate antibody response through development of ADAs.	Week 50