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

NCT04579666 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: APL2-ALS-206
• Study Type: interventional
• Target: 249
• Locations: 14 countries
• Sites: 60

Brief Summary

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)

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Keywords

Amyotrophic Lateral Sclerosis; ALS; Motor Neuron Disease; APL-2; APL2; Pegcetacoplan

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (11)

• RTP: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score at Week 52

  Baseline (Day 1) and Week 52

• RTP: Change From Baseline in Percent Predicted Slow Vital Capacity (%SVC) at Week 52

  Baseline (Day 1) and Week 52

• RTP: Change From Baseline in Muscle Strength at Week 52

  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

  Baseline (Day 1) up to Week 52

• RTP: Change From Baseline in ALS Assessment Questionnaire (ALSAQ)-40 at Week 52

  Baseline (Day 1) and Week 52

Study Arms (2)

1,080 mg pegcetacoplan (APL-2)

EXPERIMENTAL

administered subcutaneously twice weekly

Drug: Pegcetacoplan (APL-2)

Placebo administered subcutaneously twice weekly

PLACEBO COMPARATOR

Other: Placebo

Interventions

Pegcetacoplan (APL-2) DRUG

Complement (C3) Inhibitor

1,080 mg pegcetacoplan (APL-2)

Placebo OTHER

Sterile solution of equal volume to active arm

Placebo administered subcutaneously twice weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (60)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

The Berman Center

Minneapolis, Minnesota, 55415, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Austin Neuromuscular Center

Austin, Texas, 78756, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Brain and Mind Centre

Camperdown, New South Wales, 2050, Australia

Location

Central Coast Neurosciences Research

Erina, New South Wales, 2250, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

Nueor-Immunology Clinical Researh Education and Support Service (N-CRESS), Austin Health

Heidelberg, Victoria, 3084, Australia

Location

AZ Sint-Lucas & Volkskliniek

Ghent, B-9000, Belgium

Location

Universitaire Ziekenhuizen Leuven (UZ Leuven)

Leuven, B-3000, Belgium

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 21, Czechia

Location

FORBELI s.r.o.

Prague, 160 00, Czechia

Location

Hopital Pellegrin

Bordeaux, 33076, France

Location

Hôpital Neurologique Pierre Wertheimer

Bron, 69677, France

Location

CHU Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

Hôpital Roger Salengro

Lille, 59037, France

Location

CHU de Limoges Dupuytren 1

Limoges, 87042, France

Location

CHU de Nice Hôpital Pasteur

Nice, 6300, France

Location

Charité - Universitätsmedizin Berlin

Berlin, D-13353, Germany

Location

Medizinische Hochschule Hannover Klinik für Neurologie

Hanover, 30625, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Universitätsmedizin Rostock, Klinik und Poliklinik für Neurologie

Rostock, 18147, Germany

Location

University of Ulm

Ulm, 89081, Germany

Location

Beaumont Hospital

Dublin, DO9 V2NO, Ireland

Location

Ospedale Niguarda - Nemo Clinical Center - Fondazione Serena Onlus

Milan, 20162, Italy

Location

Ospedale Civile S. Agostino Estense di Modena, Azienda Ospedaliero Universitaria di Modena

Modena, 41126, Italy

Location

AOUP "P. Giaccone"

Palermo, 90129, Italy

Location

Azienda Ospedaliera Universitaria di Torino - Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

National Hospital Organization Higashinagoya National Hospital

Aichi, 465-8620, Japan

Location

National Hospital Organization Omuta National Hospital

Fukuoka, 837-0911, Japan

Location

National Hospital Organization Asahikawa Medical Center

Hokkaido, 070-8644, Japan

Location

National Hospital Organization Hyogo-Chuo National Hospital

Hyōgo, 669-1592, Japan

Location

National Hospital Organization Iou National Hospital

Ishikawa, 920-0192, Japan

Location

National Hospital Organization Matsumoto Medical Center

Matsumoto, 399-8701, Japan

Location

Niigata National Hospital National Hospital Organization

Niigata, 945-8585, Japan

Location

National Hospital Organization Okinawa National Hospital

Okinawa, 901-2214, Japan

Location

National Hospital Organization Higashisaitama National Hospital

Saitama, 349-0196, Japan

Location

Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, 420-8688, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Uniwersytecki Szpital Kliniczny w Olsztynie Klinika Neurologii

Olsztyn, 10-082, Poland

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-684, Poland

Location

City Clinic Sp. z o.o.

Warsaw, 02-473, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Bellvitge University Hospital

Barcelona, 08907, Spain

Location

Hospital Universitari I Politecnic La Fe

Valencia, 46026, Spain

Location

SI Institute of Neurology, Psychiatry and Narcology of NAMSU

Kharkiv, 61068, Ukraine

Location

Centre of Reconstructive and Restorative Medicine (University Clinic) Odessa National Medical University

Odesa, 65062, Ukraine

Location

Zaporizhzhya Regional Clinical Hospital

Zaporizhzhya, 69600, Ukraine

Location

University Hospitals Sussex NHS Foundation Trust

Brighton, BN2 5BE, United Kingdom

Location

Maurice Wohl Clinical Neuroscience Institute, King's College London

London, SE5 9RX, United Kingdom

Location

St George's University Hospitals NHS Foundation Trust

London, SW17 0WT, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

pegcetacoplan

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

The study was terminated early, during the OLP, due to lack of efficacy as determined by the Week 52 data and no safety concerns.

Results Point of Contact

• Title: Apellis Clinical Trial Information Line
• Organization: Apellis Pharmaceuticals, Inc

clinicaltrials@apellis.com

1-833-284-6361

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: October 8, 2020
• Study Start: September 30, 2020
• Primary Completion: March 31, 2023
• Study Completion: July 13, 2023
• Last Updated: April 24, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-04

Locations

AU (5); JP (12); PL (3); ES (3); IT (4); UA (3); GB (3); BE (2); IE (1); US (10); FR (6); CZ (2); NL (1); DE (5)