MERIDIAN: A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults With Amyotrophic Lateral Sclerosis (ALS)
- Conditions
- Amyotrophic Lateral SclerosisMotor Neuron Disease
- Interventions
- Other: Placebo
- Registration Number
- NCT04579666
- Lead Sponsor
- Apellis Pharmaceuticals, Inc.
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 249
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1,080 mg pegcetacoplan (APL-2) Pegcetacoplan (APL-2) administered subcutaneously twice weekly Placebo administered subcutaneously twice weekly Placebo -
- Primary Outcome Measures
Name Time Method RTP: Combined Assessment of Function and Survival (CAFS) Rank Score (Joint-Rank Score) at Week 52 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.
RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) From first dose of study drug (Day 1) up to 56 days post last dose of study drug, approximately 60 weeks 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.
OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events From first dose of study drug (Week 52) up to 56 days post last dose of study drug, approximately 60 weeks 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.
RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52 Baseline (Day 1) 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.
OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104 From Baseline (Week 52) 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.
- Secondary Outcome Measures
Name Time Method 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 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.
RTP: Change From Baseline in Percent Predicted Slow Vital Capacity (%SVC) at Week 52 Baseline (Day 1) and 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.
RTP: Change From Baseline in Muscle Strength at Week 52 Baseline (Day 1) and 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.
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 Subjects with an event (that is, either death or permanent tracheostomy or permanent assisted ventilation) in RTP are reported.
RTP: Change From Baseline in ALS Assessment Questionnaire (ALSAQ)-40 at Week 52 Baseline (Day 1) and 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.
OLP: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Score at Week 104 Baseline (Week 52) and 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.
OLP: Change From Baseline in Percent Predicted Slow Vital Capacity at Week 104 Baseline (Week 52) and 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.
OLP: Change From Baseline in Muscle Strength at Week 104 Baseline (Week 52) and 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.
OLP: Number of Subjects With an Event of Death or Permanent Tracheostomy or Permanent Assisted Ventilation at Week 104 Baseline (Week 52) and 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.
OLP: Change From Baseline in ALS Assessment Questionnaire-40 at Week 104 Baseline (Week 52) and 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.
Number of Subjects With an Event of Death During the Study RTP: Baseline (Day 1) up to Week 52; OLP: Baseline (Week 52) up to Week 104 Total number of subjects who died in the study are reported.
Trial Locations
- Locations (60)
Brain and Mind Centre
🇦🇺Camperdown, New South Wales, Australia
Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
The Berman Center
🇺🇸Minneapolis, Minnesota, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Austin Neuromuscular Center
🇺🇸Austin, Texas, United States
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Central Coast Neurosciences Research
🇦🇺Erina, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Nueor-Immunology Clinical Researh Education and Support Service (N-CRESS), Austin Health
🇦🇺Heidelberg, Victoria, Australia
AZ Sint-Lucas & Volkskliniek
🇧🇪Gent, Belgium
Universitaire Ziekenhuizen Leuven (UZ Leuven)
🇧🇪Leuven, Belgium
Hopital Pellegrin
🇫🇷Bordeaux, France
FORBELI s.r.o.
🇨🇿Prague 6, Czechia
CHU Gabriel Montpied
🇫🇷Clermont-Ferrand, France
Vseobecna fakultni nemocnice v Praze
🇨🇿Prague 2, Czechia
Hôpital Neurologique Pierre Wertheimer
🇫🇷Bron, France
Hôpital Roger Salengro
🇫🇷Lille, France
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
CHU de Nice Hôpital Pasteur
🇫🇷Nice, France
Medizinische Hochschule Hannover Klinik für Neurologie
🇩🇪Hannover, Germany
Universitätsklinikum Jena
🇩🇪Jena, Germany
Universitätsmedizin Rostock, Klinik und Poliklinik für Neurologie
🇩🇪Rostock, Germany
University of Ulm
🇩🇪Ulm, Germany
Beaumont Hospital
🇮🇪Dublin, Ireland
Ospedale Niguarda - Nemo Clinical Center - Fondazione Serena Onlus
🇮🇹Milano, Italy
Ospedale Civile S. Agostino Estense di Modena, Azienda Ospedaliero Universitaria di Modena
🇮🇹Modena, Italy
AOUP "P. Giaccone"
🇮🇹Palermo, Italy
Azienda Ospedaliera Universitaria di Torino - Città della Salute e della Scienza di Torino
🇮🇹Torino, Italy
National Hospital Organization Higashinagoya National Hospital
🇯🇵Aichi, Japan
National Hospital Organization Omuta National Hospital
🇯🇵Fukuoka, Japan
National Hospital Organization Asahikawa Medical Center
🇯🇵Hokkaido, Japan
National Hospital Organization Iou National Hospital
🇯🇵Ishikawa, Japan
National Hospital Organization Matsumoto Medical Center
🇯🇵Matsumoto, Japan
National Hospital Organization Hyogo-Chuo National Hospital
🇯🇵Hyōgo, Japan
Niigata National Hospital National Hospital Organization
🇯🇵Niigata, Japan
National Hospital Organization Okinawa National Hospital
🇯🇵Okinawa, Japan
National Hospital Organization Higashisaitama National Hospital
🇯🇵Saitama, Japan
Shizuoka Institute of Epilepsy and Neurological Disorders
🇯🇵Shizuoka, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Uniwersytecki Szpital Kliniczny w Olsztynie Klinika Neurologii
🇵🇱Olsztyn, Poland
Centrum Medyczne NeuroProtect
🇵🇱Warsaw, Poland
City Clinic Sp. z o.o.
🇵🇱Warsaw, Poland
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Centre of Reconstructive and Restorative Medicine (University Clinic) Odessa National Medical University
🇺🇦Odessa, Ukraine
Zaporizhzhya Regional Clinical Hospital
🇺🇦Zaporizhzhya, Ukraine
Bellvitge University Hospital
🇪🇸Barcelona, Spain
SI Institute of Neurology, Psychiatry and Narcology of NAMSU
🇺🇦Kharkiv, Ukraine
Hospital Universitari I Politecnic La Fe
🇪🇸Valencia, Spain
Maurice Wohl Clinical Neuroscience Institute, King's College London
🇬🇧London, United Kingdom
University Hospitals Sussex NHS Foundation Trust
🇬🇧Brighton, United Kingdom
CHU de Limoges Dupuytren 1
🇫🇷Limoges, France
St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
University of Colorado
🇺🇸Aurora, Colorado, United States
University of South Florida
🇺🇸Tampa, Florida, United States
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands