An Efficacy and Safety Study of Ravulizumab in ALS Participants

• ClinicalTrials.gov Identifier: NCT04248465
• Recruitment Status: Terminated
• First Posted: January 30, 2020
• Results First Posted: January 10, 2023
• Last Update Posted: January 10, 2023
• Sponsor: Alexion Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Alexion Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: January 27, 2020
• First Posted Date: January 30, 2020
• Results First Submitted Date: September 22, 2022
• Results First Posted Date: January 10, 2023
• Last Update Posted Date: January 10, 2023
• Actual Study Start Date: March 30, 2020
• Actual Primary Completion Date: October 17, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 22, 2022)

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.

• Original Primary Outcome Measures (submitted: January 29, 2020): Change From Baseline In Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score [ Time Frame: Baseline, Week 50 ]

Current Secondary Outcome Measures (submitted: December 15, 2022)

• 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.
• 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.
• 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.
• 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.
• Change From Baseline In Serum Neurofilament Light Chain [ Time Frame: Baseline, Week 50 ]
• Change From Baseline in Serum Ravulizumab Concentration Over the Study Duration [ Time Frame: Baseline, Predose at Week 50 ]
• Change From Baseline in Serum Free Complement Component 5 (C5) Concentration Over the Study Duration [ Time Frame: Baseline, Predose at Week 50 ]
• 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.

Original Secondary Outcome Measures (submitted: January 29, 2020)

• Time To Ventilator Assistance-free Survival [ Time Frame: Up to Week 50 ]
• Change From Baseline In Slow Vital Capacity [ Time Frame: Baseline, Week 50 ]
• Incidence Of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events, And TEAEs Leading To Study Drug Discontinuation [ Time Frame: Baseline through Week 156 ]
• Change From Baseline In Muscle Strength As Assessed By Handheld Dynamometry [ Time Frame: Baseline, Week 50 ]
• Change From Baseline In Serum Neurofilament Light Chain [ Time Frame: Baseline, Week 50 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Amyotrophic Lateral Sclerosis
• ALS

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.
  Other Names:

  • ALXN1210
  • Ultomiris

Study Arms

• Experimental: Ravulizumab
  Participants will receive ravulizumab for the duration of the study.
  Intervention: Biological: Ravulizumab
• 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.
  Interventions:

  • Drug: Placebo
  • Biological: Ravulizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 17, 2021): 382
• Original Estimated Enrollment (submitted: January 29, 2020): 354
• Actual Study Completion Date: October 17, 2021
• Actual Primary Completion Date: October 17, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Denmark, France, Germany, Ireland, Israel, Italy, Japan, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04248465
• Other Study ID Numbers: ALXN1210-ALS-308; 2019-004619-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alexion Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alexion Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Alexion Pharmaceuticals, Inc.
• Verification Date: December 2022