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

Amyotrophic Lateral Sclerosis Clinical Trial

— CARDINALS  

Official title:

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Assess the Efficacy, Safety, Tolerability, PK, and Biomarker Effects of PTC857 in Adult Subjects With Amyotrophic Lateral Sclerosis (CARDINALS)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05349721
• Other study ID #: PTC857-CNS-001-ALS
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 15, 2022
• Est. completion date: February 28, 2025

Study information

• Verified date: March 2024
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 258
• Est. completion date: February 28, 2025
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Key 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 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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• PTC857
PTC8657 will be administered as an oral solution twice a day.
• Placebo
Matching placebo will be administered as an oral solution twice a day.

Locations

Country	Name	City	State
Argentina	Iadin Srl.	Buenos Aires
Argentina	Hospital Ramos Mejía	Ciudad Autonoma de Buenos Aires
Argentina	STAT Research S.A.	Ciudad Autónoma de Buenos Aires	Buenos Aires
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Calvary Health Care Bethlehem	Caulfield South	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Gold Coast Hospital	Southport	Queensland
Belgium	AZ Sint-Lucas Gent	Gent
Belgium	UZ Leuven	Leuven
Czechia	University hospital Brno, Department of Neurology	Brno
Czechia	FORBELI s.r.o.	Prague 6
France	CHU de Bordeaux	Bordeaux Cedex
France	Hôpital Neurologique Pierre Wertheimer	Bron Cedex
France	CHU Gabriel Montpied	Clermont-Ferrand
France	CHRU Lille - Hôpital Roger Salengro	Lille Cedex
France	CHU Dupuytren 1 Limoges	Limoges
France	CHU Gui de Chauliac (Pharmacie Saint-Eloi & Gui de Chauliac, Hopital Saint-Eloi)	Montpellier
France	CRMR SLA - MNM du CHU de Nice	Nice
Germany	Charite - Universitatsmedizin - Berlin	Berlin
Germany	Hannover Medical School	Hannover
Germany	University Hospital Jena	Jena
Germany	Universitaetsklinikum Schleswig-Holstein (UKSH) Campus Luebeck, Klinik fuer Neurologie, Praezisionsneurologie	Lubeck
Germany	University of Ulm, Dept. of Neurology	Ulm
Italy	Centro Clinico Nemo Brescia	Brescia
Italy	Istituti Clinici Scientifici Maugeri IRCCS	Milano
Italy	Istituto Auxolgoico Italiano	Milano
Italy	Azienda Ospedaliero Universitaria di Modena	Modena
Italy	Maggiore della Carita University Hospital, Neurology department, ALS center	Novara
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	AOU Citta Della Salute e Scienza	Torino
Japan	PTC Clinical Site	Japanese City
Netherlands	UMC Utrecht	Utrecht
Poland	City Clinic Research Sp. Z o.o	Warsaw
Poland	Centrum Medyczne Neuro Protect	Warszawa
Spain	H. St Pau	Barcelona
Spain	Unidad Neuromuscular. Servicio de Neurologia Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Sweden	Skanes universitetssjukhus, VE Neurologi	Malmo
Sweden	Norrlands universitetssjukhus Neurologens Forskningsavdelning	Umea
United States	Augusta University	Augusta	Georgia
United States	National Neuromuscular Research Institute	Austin	Texas
United States	Henry Ford Health System Department of Neurology	Detroit	Michigan
United States	Holy Cross Hospital, Phil Smith Neuroscience Institute	Fort Lauderdale	Florida
United States	Nerve and Muscle Center of Texas	Houston	Texas
United States	University of Kansas Medical Center (KUMC) - Landon Center on Aging	Kansas City	Kansas
United States	Neurology Associates, P.C. / Somnos Clinical Research	Lincoln	Nebraska
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Health ALS and Neuromuscular Center	Orange	California
United States	Lewis Katz School of Medicine at Temple Universtiy	Philadelphia	Pennsylvania
United States	Providence Brain and Spine Institute	Portland	Oregon
United States	Forbes Norris MDA/ALS Research Center at California Pacific Medical Center	San Francisco	California
United States	University of South Florida - Carol and Frank Morsani Center for Advanced Healthcare	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Czechia,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) Score at Week 24 (Intention-to-Treat [ITT] 1 Analysis Population)	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.	Baseline, Week 24
Secondary	Change from Baseline in ALSFRS-R Score at Week 24 (ITT2 Analysis Population)	The ITT2 analysis population will include all participants who receive at least 1 dose of study drug.	Baseline, Week 24
Secondary	Number of Participants with Treatment-emergent Adverse Events		Day 1 through Week 52
Secondary	Change from Baseline in Slow Vital Capacity at Week 24		Baseline, Week 24
Secondary	Change from Baseline in Sniff Nasal Inspiratory Pressure at Week 24		Baseline, Week 24
Secondary	Change from Baseline in Modified Norris Scale Score at Week 24		Baseline, Week 24
Secondary	Change from Baseline in ALS Cognitive Behavioral Screen Assessment at Week 24		Baseline, Week 24
Secondary	Rate of Needing Respiratory Support/Intubation and/or Death		Baseline, Week 24
Secondary	Length of Time to Needing Respiratory Support/Intubation and/or Death		Baseline, Week 24
Secondary	Combined Assessment of Function and Survival (CAFS) Score		Week 24
Secondary	Change from Baseline in ALS Assessment Questionnaire (ALSAQ-40) Score at Week 24		Baseline, Week 24
Secondary	Area under the Concentration-time Curve (AUC) of PTC857 in Plasma		Predose through Week 24
Secondary	Maximum Observed Concentration (Cmax) of PTC857 in Plasma		Predose through Week 24
Secondary	AUC of PTC857 in Cerebrospinal Fluid (CSF)		Predose through Week 24
Secondary	Cmax of PTC857 in CSF		Predose through Week 24