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An Efficacy and Safety Study of Ravulizumab in ALS Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04248465
Recruitment Status : Terminated (The IDMC recommended the study be discontinued due to lack of efficacy with ravulizumab.)
First Posted : January 30, 2020
Results First Posted : January 10, 2023
Last Update Posted : January 10, 2023
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis ALS Drug: Placebo Biological: Ravulizumab Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 382 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 30, 2020
Actual Primary Completion Date : October 17, 2021
Actual Study Completion Date : October 17, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ravulizumab

Arms and Interventions
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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:
  • ALXN1210
  • Ultomiris
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.
 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.
Other Names:
  • ALXN1210
  • Ultomiris


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score [ Time Frame: 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 :
  1. Time To Ventilator Assistance-free Survival [ Time Frame: 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.

  2. Change From Baseline In Percent Predicted Slow Vital Capacity [ Time Frame: Baseline, Week 50 ]
    Slow vital capacity measures slow and gradual expulsion of air from the lungs using a spirometer.

  3. Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events, and TEAEs Leading To Study Drug Discontinuation [ Time Frame: 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.

  4. Change From Baseline In Muscle Strength As Assessed By Handheld Dynamometry [ Time Frame: 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.

  5. Change From Baseline In Serum Neurofilament Light Chain [ Time Frame: Baseline, Week 50 ]
  6. Change From Baseline in Serum Ravulizumab Concentration Over the Study Duration [ Time Frame: Baseline, Predose at Week 50 ]
  7. Change From Baseline in Serum Free Complement Component 5 (C5) Concentration Over the Study Duration [ Time Frame: Baseline, Predose at Week 50 ]
  8. Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1210 [ Time Frame: Week 50 ]
    Blood samples were collected to evaluate antibody response through development of ADAs.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04248465


Locations
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Sponsors and Collaborators
Alexion Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals, Inc.:
Study Protocol  [PDF] June 23, 2021
Statistical Analysis Plan  [PDF] November 18, 2021

More Information
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Responsible Party: Alexion Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04248465    
Other Study ID Numbers: ALXN1210-ALS-308
2019-004619-30 ( EudraCT Number )
First Posted: January 30, 2020    Key Record Dates
Results First Posted: January 10, 2023
Last Update Posted: January 10, 2023
Last Verified: December 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alexion Pharmaceuticals, Inc.:
Ravulizumab
ALXN1210
Ultomiris
 Motor Neuron Disease
Amyotrophic Lateral Sclerosis
ALS
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
 TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Ravulizumab
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs