Study to Assess the Effects of PTC857 Treatment in Participants With Amyotrophic Lateral Sclerosis ALS

NCT05349721 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: PTC857-CNS-001-ALS2021-006511-292023-510317-26-00
• Study Type: interventional
• Target: 336
• Locations: 13 countries
• Sites: 55

Brief Summary

This study will assess the efficacy and safety of PTC857 treatment in participants diagnosed with ALS.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Combined Assessment of Function (ALS Functional Rating Scale-Revised [ALSFRS-R]) and Survival (CAFS) Rank After 24 Weeks of Treatment (Intention-to-Treat [ITT] 1 Analysis Population)

  The CAFS is a composite endpoint based on time to earlier occurrence of death and change from baseline in ALSFRS-R score. ALSFRS-R is a rating scale where 12 functions were rated on 5-point scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items), with a higher score indicating better function. Each participant's outcome was compared to every other participant's outcome in a pairwise fashion by time to death and change on ALSFRS-R, assigned a score which was sum of comparisons (+1 \[better\], 0 \[tie\], -1 \[worse\]), and summed scores were ranked, from 1 to 306 (ITT1 Analysis Set) lowest rank corresponds to participant who died first and highest rank to the participant with best ALSFRS-R outcome among those who survived. Multiple imputation was used to impute participants with missing ALSFRS-R score at Week 24. A higher rank was considered a better outcome. Least square (LS) means and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.

  Week 24

Secondary Outcomes (13)

• Combined Assessment of Function (ALSFRS-R) and Survival (CAFS) Rank After 24 Weeks of Treatment (ITT2 Analysis Population)

  Week 24

• Change From Baseline in ALSFRS-R Score at Week 24 (ITT1 Analysis Population)

  Baseline, Week 24

• Change From Baseline in ALSFRS-R Score at Week 24 (ITT2 Analysis Population)

  Baseline, Week 24

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Day 1 through Week 24

• Change From Baseline in Percent Predicted Slow Vital Capacity (SVC) at Week 24

  Baseline, Week 24

Study Arms (2)

PTC857

EXPERIMENTAL

Participants will receive PTC857 during the 24-Week Treatment Period. Following successful completion of the Treatment Period, participants who enter the Long-term Extension (LTE) Period, will receive open-label PTC857 for 28 weeks. Following completion of the LTE period, participants who enter the Continued LTE Period will receive open-label PTC857 for an additional 108 weeks.

Drug: PTC857

Placebo

ACTIVE COMPARATOR

Participants will receive matching placebo during the 24-Week Treatment Period. Following successful completion of the Treatment Period, participants who enter the LTE Period, will receive open-label PTC857 for 28 weeks. Following completion of the LTE period, participants who enter the Continued LTE Period will receive open-label PTC857 for an additional 108 weeks.

Drug: Placebo

Interventions

PTC857 DRUG

PTC8657 will be administered as an oral solution twice a day.

PTC857

Placebo DRUG

Matching placebo will be administered as an oral solution twice a day.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ALS with preserved function, defined as:
• Onset of the first symptom leading to the diagnosis of ALS ≤24 months at the time of the initial Screening Visit
• Revised EL Escorial criteria of either:
• (i) Clinically definite ALS (ii) Clinically probable ALS
• A total ALSFRS-R score of at least 34 at the start of the Screening Period
• No significant respiratory compromise as evidenced by slow vital capacity ≥60% at the start of the Screening Period
• All chronic concomitant medications (both prescription and over the counter), and non-pharmacologic therapy regimens, excluding standard-of-care therapy riluzole, edaravone, or sodium phenylbutyrate/taurursodiol, should be stable and unchanged from 14 days prior to the start of the Screening Period and intend to remain stable and unchanged throughout the course of the study
• Female participants must have a negative breast cancer imaging screening status (not considered clinically abnormal and/or requiring further evaluation/treatment) within 6 months prior to the Screening Visit, or during the Screening Period.
• Standard-of-care therapy for the treatment of ALS (riluzole, edaravone, or sodium phenylbutyrate/taurursodiol) should be stable and unchanged from 30 (-3) days prior to the start of the Screening Period and intend to remain stable and unchanged throughout the course of the study.

You may not qualify if:

• Females who are pregnant or nursing or plan to become pregnant during the study
• Participants with clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular/ischemic disease or any other condition that, in the opinion of the investigator would jeopardize the safety of the participant or impact the validity of the study results
• Any clinically significant medical or psychiatric condition or medical history that, in the opinion of the investigator or the medical monitor, would interfere with the participant's ability to participate in the study or increase the risk of participation for that participant
• Current participation in any other investigational study with an investigational product or participation within 30 days prior to the start of the Screening Period or 5 half-lives of the previously taken investigational drug, whichever is longer
• Participant has previously received PTC857
• Participant is receiving a combination of edaravone and sodium phenylbutyrate/taurursodiol treatment, where applicable, within 30 days prior to the start of the Screening Period
• For female participants, any past medical history of breast cancer, regardless of remission status, or any first degree relative with history of breast cancer

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (55)

UC Irvine Health ALS and Neuromuscular Center

Orange, California, 92868, United States

Location

Forbes Norris MDA/ALS Research Center at California Pacific Medical Center

San Francisco, California, 94109, United States

Location

Holy Cross Hospital, Phil Smith Neuroscience Institute

Fort Lauderdale, Florida, 33308, United States

Location

University of South Florida - Carol and Frank Morsani Center for Advanced Healthcare

Tampa, Florida, 33612, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

University of Kansas Medical Center (KUMC) - Landon Center on Aging

Kansas City, Kansas, 66205, United States

Location

Henry Ford Health System Department of Neurology

Detroit, Michigan, 48202, United States

Location

Neurology Associates, P.C. / Somnos Clinical Research

Lincoln, Nebraska, 68506, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-8440, United States

Location

Providence Brain and Spine Institute

Portland, Oregon, 97213, United States

Location

Lewis Katz School of Medicine at Temple Universtiy

Philadelphia, Pennsylvania, 19140, United States

Location

National Neuromuscular Research Institute

Austin, Texas, 78759, United States

Location

Nerve and Muscle Center of Texas

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

STAT Research S.A.

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1023AAB, Argentina

Location

Iadin Srl.

Buenos Aires, C1015ABR, Argentina

Location

Hospital Ramos Mejía

Buenos Aires, CP 1221, Argentina

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Gold Coast Hospital

Southport, Queensland, 4215, Australia

Location

Calvary Health Care Bethlehem

Caulfield South, Victoria, 3162, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

AZ Sint-Lucas Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

University hospital Brno, Department of Neurology

Brno, 62500, Czechia

Location

FORBELI s.r.o.

Prague, 160 00, Czechia

Location

CHU de Bordeaux

Bordeaux, 33076, France

Location

Hôpital Neurologique Pierre Wertheimer

Bron, 69677, France

Location

CHU Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

CHRU Lille - Hôpital Roger Salengro

Lille, 59037, France

Location

CHU Dupuytren 1 Limoges

Limoges, 87000, France

Location

CHU Gui de Chauliac (Pharmacie Saint-Eloi & Gui de Chauliac, Hopital Saint-Eloi)

Montpellier, 34295, France

Location

CRMR SLA - MNM du CHU de Nice

Nice, 06200, France

Location

Charite - Universitatsmedizin - Berlin

Berlin, 13353, Germany

Location

Hannover Medical School

Hanover, 30625, Germany

Location

University Hospital Jena

Jena, 7747, Germany

Location

Universitaetsklinikum Schleswig-Holstein (UKSH) Campus Luebeck, Klinik fuer Neurologie, Praezisionsneurologie

Lübeck, 23538, Germany

Location

University of Ulm, Dept. of Neurology

Ulm, 89081, Germany

Location

Centro Clinico Nemo Brescia

Brescia, 25123, Italy

Location

Istituti Clinici Scientifici Maugeri IRCCS

Milan, 20138, Italy

Location

Istituto Auxolgoico Italiano

Milan, 20149, Italy

Location

Azienda Ospedaliero Universitaria di Modena

Modena, 41126, Italy

Location

Maggiore della Carita University Hospital, Neurology department, ALS center

Novara, 28100, Italy

Location

ALS Clinical Research Center, University Hospital Policlinico "P Giaccone"

Palermo, 90127, Italy

Location

IRCCS Fondazione Mondino - Reparto Neuroncologia/Neuroinfiammazione

Pavia, 27100, Italy

Location

Policlinico Umberto I

Roma, 00161, Italy

Location

AOU Citta Della Salute e Scienza

Torino, 10126, Italy

Location

PTC Clinical Site

Japanese City, Japan

Location

UMC Utrecht

Utrecht, 3584 CW, Netherlands

Location

Centrum Medyczne Neuro Protect

Warsaw, 01-684, Poland

Location

City Clinic Research Sp. Z o.o

Warsaw, 02-473, Poland

Location

Unidad Neuromuscular. Servicio de Neurologia Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

H. St Pau

Barcelona, 08041, Spain

Location

Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

Location

Skanes universitetssjukhus, VE Neurologi

Malmo, SE-211 24, Sweden

Location

Norrlands universitetssjukhus Neurologens Forskningsavdelning

Umeå, 90185, Sweden

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study was terminated early due to company decision.

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• 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: April 21, 2022
• First Posted: April 27, 2022
• Study Start: May 15, 2022
• Primary Completion: September 26, 2024
• Study Completion: January 30, 2025
• Last Updated: August 1, 2025
• Results First Posted: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); AR (3); IT (9); FR (7); US (14); AU (4); DE (5); BE (2); NL (1); ES (3); PL (2); CZ (2); JP (1)