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
    • Hôpital Pellegrin
  • Bron, France, 69677
    • Hôpital Neurologique Pierre Wertheimer
  • Clermont-Ferrand, France, 63000
    • CHU Gabriel Montpied
  • Lille, France, 59037
    • Hopital Roger Salengro
  • Limoges, France, 87042
    • CHU de Limoges Dupuytren 1
  • Nice, France, 6300
    • CHU de Nice Hopital Pasteur
• Germany
  • Berlin, Germany, D-13353
    • Charité - Universitätsmedizin Berlin
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover Klinik Fur Neurologie
  • Jena, Germany, 07747
    • Universitatsklinikum 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 Politecnic 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
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

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): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; Motor Neuron Disease; APL-2; APL2; Pegcetacoplan
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular 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