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

Phase 2

Active, not recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: PTC857; Drug: Placebo

• Registration Number: NCT05349721
• Lead Sponsor: PTC Therapeutics

Brief Summary

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

Detailed Description

Participants will be randomized to 1 of the 2 treatment groups: PTC857 or matching placebo. 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.

Study Timeline

• Study First Submitted: 2022-04-21
• Study First Submitted QC: 2022-04-21
• Study First Posted: 2022-04-27
• Study Start: 2022-05-15
• Status Verified: 2024-08
• Primary Completion: 2024-09-26
• Last Update Submitted: 2024-10-01
• Last Update Posted: 2024-10-03
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 307

Inclusion Criteria

• ALS with preserved function, defined as:

  1. Onset of the first symptom leading to the diagnosis of ALS ≤24 months at the time of the initial Screening Visit
  2. 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.

Key

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Exclusion Criteria

• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PTC857	PTC857	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.
Placebo	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Participant Ranks Based on the Combined Assessment of ALS Functional Rating Scale-Revised (ALSFRS-R) and Survival After 24 Weeks of Treatment (Intention-to-Treat [ITT] 1 Analysis Population)	Week 24	The ITT1 analysis population will include all participants who receive at least 1 dose of study drug and have a decrease in the ALSFRS-R score of between 1 and 4 points (inclusive) during the Screening Period.

Secondary Outcome Measures

Name	Time	Method
Participant Ranks Based on the Combined Assessment of ALSFRS-R and Survival After 24 Weeks of Treatment (ITT 2 Analysis Population)	Week 24	The ITT2 analysis population will include all participants who receive at least 1 dose of study drug.
Change from Baseline in ALSFRS-R Score at Week 24 (ITT1 Analysis Population)	Baseline, Week 24	The ITT1 analysis population will include all participants who receive at least 1 dose of study drug and have a decrease in the ALSFRS-R score of between 1 and 4 points (inclusive) during the Screening Period.
Change from Baseline in ALSFRS-R Score at Week 24 (ITT2 Analysis Population)	Baseline, Week 24	The ITT2 analysis population will include all participants who receive at least 1 dose of study drug.
Number of Participants with Treatment-emergent Adverse Events	Day 1 through Week 52
Change from Baseline in Slow Vital Capacity at Week 24	Baseline, Week 24
Change from Baseline in Sniff Nasal Inspiratory Pressure at Week 24	Baseline, Week 24
Change from Baseline in Modified Norris Scale Score at Week 24	Baseline, Week 24
Rate of Death	Baseline to Week 24
Length of Time to Death	Baseline to Week 24
Change from Baseline in ALS Assessment Questionnaire (ALSAQ-40) Score at Week 24	Baseline, Week 24
Change From Baseline in Neurofilament Light Chain (NfL) Activity at Week 24	Baseline, Week 24
Area under the Concentration-time Curve (AUC) of PTC857 in Plasma	Predose through Week 24
Maximum Observed Concentration (Cmax) of PTC857 in Plasma	Predose through Week 24
AUC of PTC857 in Cerebrospinal Fluid (CSF)	Predose through Week 24
Cmax of PTC857 in CSF	Predose through Week 24

Trial Locations

Locations (55)

Unidad Neuromuscular. Servicio de Neurologia Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Maggiore della Carita University Hospital, Neurology department, ALS center; 🇮🇹 Novara, Italy

AOU Citta Della Salute e Scienza; 🇮🇹 Torino, Italy

City Clinic Research Sp. Z o.o; 🇵🇱 Warsaw, Poland

Centrum Medyczne Neuro Protect; 🇵🇱 Warszawa, Poland

Azienda Ospedaliero Universitaria di Modena; 🇮🇹 Modena, Italy

PTC Clinical Site; 🇯🇵 Japanese City, Japan

UMC Utrecht; 🇳🇱 Utrecht, Netherlands

H. St Pau; 🇪🇸 Barcelona, Spain

University of Kansas Medical Center (KUMC) - Landon Center on Aging; 🇺🇸 Kansas City, Kansas, United States

Forbes Norris MDA/ALS Research Center at California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Istituto Auxolgoico Italiano; 🇮🇹 Milano, Italy

ALS Clinical Research Center, University Hospital Policlinico "P Giaccone"; 🇮🇹 Palermo, Italy

IRCCS Fondazione Mondino - Reparto Neuroncologia/Neuroinfiammazione; 🇮🇹 Pavia, Italy

Policlinico Umberto I; 🇮🇹 Roma, Italy

CHU de Bordeaux; 🇫🇷 Bordeaux Cedex, France

UC Irvine Health ALS and Neuromuscular Center; 🇺🇸 Orange, California, United States

Holy Cross Hospital, Phil Smith Neuroscience Institute; 🇺🇸 Fort Lauderdale, Florida, United States

Lewis Katz School of Medicine at Temple Universtiy; 🇺🇸 Philadelphia, Pennsylvania, United States

Augusta University; 🇺🇸 Augusta, Georgia, United States

University hospital Brno, Department of Neurology; 🇨🇿 Brno, Czechia

Nerve and Muscle Center of Texas; 🇺🇸 Houston, Texas, United States

STAT Research S.A.; 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Hospital Ramos Mejía; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Iadin Srl.; 🇦🇷 Buenos Aires, Argentina

Gold Coast Hospital; 🇦🇺 Southport, Queensland, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Calvary Health Care Bethlehem; 🇦🇺 Caulfield South, Victoria, Australia

AZ Sint-Lucas Gent; 🇧🇪 Gent, Belgium

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

UZ Leuven; 🇧🇪 Leuven, Belgium

FORBELI s.r.o.; 🇨🇿 Prague 6, Czechia

CHRU Lille - Hôpital Roger Salengro; 🇫🇷 Lille Cedex, France

Hôpital Neurologique Pierre Wertheimer; 🇫🇷 Bron Cedex, France

CHU Gabriel Montpied; 🇫🇷 Clermont-Ferrand, France

CHU Dupuytren 1 Limoges; 🇫🇷 Limoges, France

Hannover Medical School; 🇩🇪 Hannover, Germany

University Hospital Jena; 🇩🇪 Jena, Germany

CHU Gui de Chauliac (Pharmacie Saint-Eloi & Gui de Chauliac, Hopital Saint-Eloi); 🇫🇷 Montpellier, France

CRMR SLA - MNM du CHU de Nice; 🇫🇷 Nice, France

Charite - Universitatsmedizin - Berlin; 🇩🇪 Berlin, Germany

University of Ulm, Dept. of Neurology; 🇩🇪 Ulm, Germany

Universitaetsklinikum Schleswig-Holstein (UKSH) Campus Luebeck, Klinik fuer Neurologie, Praezisionsneurologie; 🇩🇪 Lubeck, Germany

Centro Clinico Nemo Brescia; 🇮🇹 Brescia, Italy

Istituti Clinici Scientifici Maugeri IRCCS; 🇮🇹 Milano, Italy

Hospital Universitario y Politecnico La Fe; 🇪🇸 Valencia, Spain

Skanes universitetssjukhus, VE Neurologi; 🇸🇪 Malmo, Sweden

Norrlands universitetssjukhus Neurologens Forskningsavdelning; 🇸🇪 Umea, Sweden

Neurology Associates, P.C. / Somnos Clinical Research; 🇺🇸 Lincoln, Nebraska, United States

University of South Florida - Carol and Frank Morsani Center for Advanced Healthcare; 🇺🇸 Tampa, Florida, United States

Henry Ford Health System Department of Neurology; 🇺🇸 Detroit, Michigan, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Providence Brain and Spine Institute; 🇺🇸 Portland, Oregon, United States

National Neuromuscular Research Institute; 🇺🇸 Austin, Texas, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States