An Efficacy and Safety Study of Ravulizumab in ALS Participants

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

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)

Conditions
-----------------
ALS, Amyotrophic Lateral Sclerosis

Intervention / Treatment
-----------------
* Drug: Placebo
* Biological: Ravulizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: A diagnosis of sporadic or familial ALS, defined by the El Escorial criteria (possible, laboratory-supported probable, probable, or definite ALS). ALS onset ≤ 36 months from Screening. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment. Upright slow vital capacity ≥ 65% predicted at Screening. 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). Body weight ≥ 40 kilograms at Screening. 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: History of Neisseria meningitidis infection. Human immunodeficiency virus (HIV) infection (evidenced by HIV 1 or HIV 2 antibody titer). Dependence on invasive or non-invasive mechanical ventilation. Previously or currently treated with a complement inhibitor. Exposure to an investigational drug or device within 30 days of Screening or 5 half lives of the study drug, whichever is greater.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ravulizumab<br>Participants will receive ravulizumab for the duration of the study. | Biological: Ravulizumab<br>* Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.<br>* Other names: Ultomiris;|
| Placebo Comparator: Placebo<br>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<br>* Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.<br>Biological: Ravulizumab<br>* Single loading dose via intravenous infusion, followed by regular maintenance dosing, based on weight.<br>* Other names: Ultomiris;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Change From Baseline In Serum Neurofilament Light Chain |  | Baseline, Week 50 | 
| Change From Baseline in Serum Ravulizumab Concentration Over the Study Duration |  | Baseline, Predose at 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 | Blood samples were collected to evaluate antibody response through development of ADAs. | Week 50 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ALS, Ravulizumab, ALXN1210, Ultomiris, Motor Neuron Disease, Amyotrophic Lateral Sclerosis