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

Study Timeline

• Study First Submitted: 2020-01-27
• Study First Submitted QC: 2020-01-29
• Study First Posted: 2020-01-30
• Study Start: 2020-03-30
• Primary Completion: 2021-10-17
• Study Completion: 2021-10-17
• Results First Submitted: 2022-09-22
• Status Verified: 2022-12
• Results First Submitted QC: 2022-12-15
• Last Update Submitted: 2022-12-15
• Results First Posted: 2023-01-10
• Last Update Posted: 2023-01-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 382

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 & 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.
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 Neurofilament Light Chain	Baseline, 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.
Change From Baseline in Serum Ravulizumab Concentration Over the Study Duration	Baseline, Predose at Week 50

Trial Locations

Locations (95)

Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

Neuromuscular Research Center and Clinic; 🇺🇸 Phoenix, Arizona, United States

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

University of California-Irvine; 🇺🇸 Orange, California, United States

Stanford University Medical Center; 🇺🇸 Palo Alto, California, 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

Scroll for more (85 remaining)