MERIDIAN: A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults With Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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This is a 24-month, Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pegcetacoplan in subjects with amyotrophic lateral sclerosis (ALS)

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Conditions
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Amyotrophic Lateral Sclerosis, Motor Neuron Disease

Intervention / Treatment
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* Drug: Pegcetacoplan (APL-2)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Sporadic ALS diagnosed as definite, probable, or laboratory-supported probable as defined by the revised El Escorial criteria Slow vital capacity (SVC) ≥60% of the predicted value at screening Onset of ALS symptoms within 72 weeks (18 months) prior to screening Total ALSFRS-R score of ≥30 at screening Have vaccination within 5 years against Streptococcus pneumoniae, Neisseria meningitidis (types A, C, W, Y, and B), and Haemophilus influenzae (type B) or agree to receive vaccination Exclusion Criteria: Confirmed or suspected other causes of neuromuscular weakness Diagnosed with another neurodegenerative disease (examples include Parkinson's disease and Huntington's disease) Significant pulmonary disorder not attributed to ALS (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension) If taking riluzole, participant must be on a stable dose for 30 days prior to the start of the screening period. Use of riluzole is not required for participation. If taking edaravone, participant must be on a stable dose for 60 days prior to the start of the screening period. Use of edaravone is not required for participation. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or within 5-half lives of the treatment (whichever is longer) prior to the start of the screening period or during study participation Use of any other complement inhibitor within 30 days or within 5-half lives of the treatment (whichever is longer) prior to the start of the screening period or during study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1,080 mg pegcetacoplan (APL-2)<br>administered subcutaneously twice weekly | Drug: Pegcetacoplan (APL-2)<br>* Complement (C3) Inhibitor<br>|
| Placebo Comparator: Placebo administered subcutaneously twice weekly<br> | Other: Placebo<br>* Sterile solution of equal volume to active arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Assessment of Function and Survival (CAFS) | Efficacy | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (TEAEs) | Safety | Up to Week 104 | 
| Number of participants with positive responses (yes) to the Columbia Suicide Severity Rating Scale (C-SSRS) |  | Up to Week 104 | 
| Change from Baseline in the Revised ALS Functional Rating scale (ALSFRS-R) score | Minimum score of 0 and maximum of 48, with higher values representing better function | Baseline, Week 52 | 
| Change from Baseline in percentage of slow vital capacity (%SVC) |  | Baseline, at Week 52 | 
| Change from Baseline in muscle strength |  | Baseline, Week 52 | 
| Time to death, permanent tracheostomy, or permanent assisted ventilation |  | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, ALS, Motor Neuron Disease, APL-2, APL2, Pegcetacoplan