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

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)

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)

Study Overview

• Status: Terminated
• Conditions: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Other: Placebo; Drug: Pegcetacoplan (APL-2)

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Brain and Mind Centre
    • Erina, New South Wales, Australia, 2250
      • Central Coast Neurosciences Research
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Nueor-Immunology Clinical Researh Education and Support Service (N-CRESS), Austin Health
• Belgium
  • Gent, Belgium, B-9000
    • AZ Sint-Lucas & Volkskliniek
  • Leuven, Belgium, B-3000
    • Universitaire Ziekenhuizen Leuven (UZ Leuven)
• Czechia
  • Prague 2, Czechia, 128 21
    • Vseobecna fakultni nemocnice v Praze
  • Prague 6, Czechia, 160 00
    • FORBELI s.r.o.
• France
  • Bordeaux, France, 33076
    • Hopital Pellegrin
  • Bron, France, 69677
    • Hopital Neurologique Pierre Wertheimer
  • Clermont-Ferrand, France, 63000
    • Chu Gabriel Montpied
  • Lille, France, 59037
    • Hôpital Roger Salengro
  • Limoges, France, 87042
    • CHU de Limoges Dupuytren 1
  • Nice, France, 6300
    • CHU de Nice Hopital Pasteur
• Germany
  • Berlin, Germany, D-13353
    • Charite - Universitätsmedizin Berlin
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover Klinik Fur Neurologie
  • Jena, Germany, 07747
    • Universitätsklinikum Jena
  • Rostock, Germany, 18147
    • Universitätsmedizin Rostock, Klinik und Poliklinik für Neurologie
  • Ulm, Germany, 89081
    • University of Ulm
• Ireland
  • Dublin, Ireland, DO9 V2NO
    • Beaumont Hospital
• Italy
  • Milano, Italy, 20162
    • Ospedale Niguarda - Nemo Clinical Center - Fondazione Serena Onlus
  • Modena, Italy, 41126
    • Ospedale Civile S. Agostino Estense di Modena, Azienda Ospedaliero Universitaria di Modena
  • Palermo, Italy, 90129
    • AOUP "P. Giaccone"
  • Torino, Italy, 10126
    • Azienda Ospedaliera Universitaria di Torino - Città della Salute e della Scienza di Torino
• Japan
  • Aichi, Japan, 465-8620
    • National Hospital Organization Higashinagoya National Hospital
  • Fukuoka, Japan, 837-0911
    • National Hospital Organization Omuta National Hospital
  • Hokkaido, Japan, 070-8644
    • National Hospital Organization Asahikawa Medical Center
  • Hyōgo, Japan, 669-1592
    • National Hospital Organization Hyogo-Chuo National Hospital
  • Ishikawa, Japan, 920-0192
    • National Hospital Organization Iou National Hospital
  • Matsumoto, Japan, 399-8701
    • National Hospital Organization Matsumoto Medical Center
  • Niigata, Japan, 945-8585
    • Niigata National Hospital National Hospital Organization
  • Okinawa, Japan, 901-2214
    • National Hospital Organization Okinawa National Hospital
  • Saitama, Japan, 349-0196
    • National Hospital Organization Higashisaitama National Hospital
  • Shizuoka, Japan, 420-8688
    • Shizuoka Institute of Epilepsy and Neurological Disorders
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
• Poland
  • Olsztyn, Poland, 10-082
    • Uniwersytecki Szpital Kliniczny w Olsztynie Klinika Neurologii
  • Warsaw, Poland, 01-684
    • Centrum Medyczne NeuroProtect
  • Warsaw, Poland, 02-473
    • City Clinic Sp. z o.o.
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Bellvitge University Hospital
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
• Ukraine
  • Kharkiv, Ukraine, 61068
    • SI Institute of Neurology, Psychiatry and Narcology of NAMSU
  • Odessa, Ukraine, 65062
    • Centre of Reconstructive and Restorative Medicine (University Clinic) Odessa National Medical University
  • Zaporizhzhya, Ukraine, 69600
    • Zaporizhzhya Regional Clinical Hospital
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • University Hospitals Sussex NHS Foundation Trust
  • London, United Kingdom, SE5 9RX
    • Maurice Wohl Clinical Neuroscience Institute, King's College London
  • London, United Kingdom, SW17 0WT
    • St George's University Hospitals NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • The Berman Center
  • New York
    • New York, New York, United States, 10021
      • Hospital For Special Surgery
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Neuromuscular Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RTP: Combined Assessment of Function and Survival (CAFS) Rank Score (Joint-Rank Score) at Week 52	The CAFS scale is a combined endpoint ranking subjects' clinical outcomes based on ALS Functional Rating Scale-Revised (ALSFRS-R-described below) and survival time. For ALSFRS-R, 12 functions were rated on 5-point ordinal rating scales (0 to 4) with a total score range of 0-48 (sum of all 12 items); higher score indicated better functioning. For survival time, longer the subject survives indicated better outcome. Each subject's outcome was compared to every other subject outcome in trial in series of pairwise comparisons, summed scores (sum of comparisons [+1 {better}, 0 {tie}, -1 {worse}]) were ranked and ranged from 001-247 (number of subjects in modified [m]ITT population).Reported values are the least squares mean rank scores in each group for the composite endpoint. Higher rank indicated better outcome.	Week 52
RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An SAE was any AE or suspected adverse reaction that, in the view of the investigator, resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital anomaly or birth defect. TEAEs were AEs that started on or after first dose of study drug or started before first dose of study drug but increased in severity on or after the first dose of study drug up to 56 days post last dose of study drug.	From first dose of study drug (Day 1) up to 56 days post last dose of study drug, approximately 60 weeks
OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events	An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An SAE was any AE or suspected adverse reaction that, in the view of the investigator, resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital anomaly or birth defect. TEAEs were AEs that started on or after first dose of study drug or started before first dose of study drug but increased in severity on or after the first dose of study drug up to 56 days post last dose of study drug.	From first dose of study drug (Week 52) up to 56 days post last dose of study drug, approximately 60 weeks
RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52	The C-SSRS is a measure used to identify and assess individuals at risk for suicide and included "yes" or "no" responses for assessment of suicidal ideation (SI) and suicidal behavior (SB).C-SSRS SI items are classified on 5-item scale:1 (wish to be dead),2 (non-specific active suicidal thoughts),3 (active SI with any methods without intent to act),4 (active SI with some intent to act, without specific plan) and 5 (active SI with a specific plan and intent).C-SSRS SB items are classified on 5-item scale: 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), 4 (actual attempt [non-fatal]) and 5 (completed suicide). Numeric ratings were provided for SI (1 to 5) and SB (1 to 5) with 5 being more severe for each. Number of subjects with a response of 'yes' to SI only, SB only & SI and SB are reported. Baseline: last available, non-missing observation prior to first study drug administration.	Baseline (Day 1) up to Week 52
OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104	The C-SSRS is a measure used to identify and assess individuals at risk for suicide and included "yes" or "no" responses for assessment of SI and SB.C-SSRS SI items are classified on 5-item scale:1 (wish to be dead),2 (non-specific active suicidal thoughts),3 (active SI with any methods without intent to act),4 (active SI with some intent to act, without specific plan) and 5 (active SI with a specific plan and intent).C-SSRS SB items are classified on 5-item scale:1 (preparatory acts or behavior),2 (aborted attempt), 3 (interrupted attempt), 4 (actual attempt [non-fatal]) and 5 (completed suicide). Numeric ratings were provided for SI (1 to 5) and SB (1 to 5) with 5 being more severe for each. Number of subjects with a response of 'yes' to SI only, SB only & SI and SB are reported. Baseline: last available, non-missing observation prior to first study drug administration in OLP.	From Baseline (Week 52) up to Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RTP: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score at Week 52	The ALSFRS-R included 12 items for assessment of functional status: speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing and hygiene, turning in bed and adjusting bed clothes, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency. Each item ranged from 0 (no ability) to 4 (normal ability). Individual item scores were summed to produce a total score between 0 (worst) and 48 (best) with higher scores meaning better outcome. Least squares mean is presented here. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (Day 1) and Week 52
RTP: Change From Baseline in Percent Predicted Slow Vital Capacity (%SVC) at Week 52	SVC is a pulmonary function test and predictor of functional loss in ALS. It was conducted at clinic visits with the clinic spirometer which reflected the maximum amount of air that could be exhaled slowly. %SVC is the actual volume exhaled in the first 1 second, divided by the normal value for that actual value for a person of that age, gender, height and weight. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (Day 1) and Week 52
RTP: Change From Baseline in Muscle Strength at Week 52	Muscle strength was measured using handheld dynamometry (HHD) and assessed the following muscles: first dorsal interosseous, wrist extension, elbow extension, elbow flexion, shoulder flexion, knee extension, knee flexion, and ankle dorsiflexion, on both sides of the body. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (Day 1) and Week 52
RTP: Number of Subjects With an Event of Death or Permanent Tracheostomy or Permanent Assisted Ventilation at Week 52	Subjects with an event (that is, either death or permanent tracheostomy or permanent assisted ventilation) in RTP are reported.	Baseline (Day 1) up to Week 52
RTP: Change From Baseline in ALS Assessment Questionnaire (ALSAQ)-40 at Week 52	The ALSAQ-40 was a 40-item validated questionnaire designed to assess health related quality of life (QoL) over the previous 2 weeks in subjects with ALS. It represented 5 dimensions of health status; each scored from 0 (never, or best) to 4 (always, or worst). 5 dimensions evaluated were: physical mobility (10 items: 1-10; possible score of 0-40); activities of daily living/independence (10 items: 11-20; possible score of 0-40); eating and drinking (3 items: 21-23; possible score of 0-12); communication (7 items: 24-30; possible score: 0-28) and emotional functioning (10 items: 31-40; possible score: 0-40). The total score 0 (no impairment) to 160 (severe impairment) was calculated by adding the 5 dimension scores; least squares mean is presented here. Higher scores indicated worse QoL.	Baseline (Day 1) and Week 52
OLP: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Score at Week 104	The ALSFRS-R included 12 items for assessment of functional status: speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing and hygiene, turning in bed and adjusting bed clothes, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency. Each item ranged from 0 (no ability) to 4 (normal ability). Individual item scores were summed to produce a total score between 0 (worst) and 48 (best) with higher scores meaning better outcome. Mean is presented here. Baseline was defined as the last observed value for the efficacy assessment prior to taking the first dose of study drug in OLP.	Baseline (Week 52) and Week 104
OLP: Change From Baseline in Percent Predicted Slow Vital Capacity at Week 104	SVC is a pulmonary function test and predictor of functional loss in ALS. It was planned to be conducted at clinic visits with the clinic spirometer which reflected the maximum amount of air that could be exhaled slowly. %SVC is the actual volume exhaled in the first 1 second, divided by the normal value for that actual value for a person of that age, gender, height and weight. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (Week 52) and Week 104
OLP: Change From Baseline in Muscle Strength at Week 104	Muscle strength was planned to be measured using HHD and assessed the following muscles: first dorsal interosseous, wrist extension, elbow extension, elbow flexion, shoulder flexion, knee extension, knee flexion, and ankle dorsiflexion, on both sides of the body. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (Week 52) and Week 104
OLP: Number of Subjects With an Event of Death or Permanent Tracheostomy or Permanent Assisted Ventilation at Week 104	Subjects with an event of death are reported. Subjects were planned to be assessed for permanent tracheostomy or permanent assisted ventilation in OLP; however, that data was not collected as study was terminated early.	Baseline (Week 52) and Week 104
OLP: Change From Baseline in ALS Assessment Questionnaire-40 at Week 104	The ALSAQ-40 was a 40-item validated questionnaire designed to assess health related QoL over the previous 2 weeks in subjects with ALS. It represented 5 dimensions of health status; each scored from 0 (never, or best) to 4 (always, or worst). 5 dimensions evaluated were: physical mobility (10 items: 1-10; possible score of 0-40); activities of daily living/independence (10 items: 11-20; possible score of 0-40); eating and drinking (3 items: 21-23; possible score of 0-12); communication (7 items: 24-30; possible score: 0-28) and emotional functioning (10 items: 31-40; possible score: 0-40). The total score 0 (no impairment) to 160 (severe impairment) was planned to be calculated by adding the 5 dimension scores. Higher scores would have indicated worse QoL.	Baseline (Week 52) and Week 104
Number of Subjects With an Event of Death During the Study	Total number of subjects who died in the study are reported.	RTP: Baseline (Day 1) up to Week 52; OLP: Baseline (Week 52) up to Week 104

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Study Website

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): July 13, 2023

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; Motor Neuron Disease; APL-2; APL2; Pegcetacoplan
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: APL2-ALS-206

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No