Clinical trial NCT05349721: Study to Assess the Effects of PTC857 Treatment in Participants With Amyotrophic Lateral Sclerosis ALS
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-04-27
Enrollment: 307
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Week 24
Secondary outcomes:
measure: Participant Ranks Based on the Combined Assessment of ALSFRS-R and Survival After 24 Weeks of Treatment (ITT 2 Analysis Population)
timeFrame: Week 24
measure: Change from Baseline in ALSFRS-R Score at Week 24 (ITT1 Analysis Population)
timeFrame: Baseline, Week 24
measure: Change from Baseline in ALSFRS-R Score at Week 24 (ITT2 Analysis Population)
timeFrame: Baseline, Week 24
measure: Number of Participants with Treatment-emergent Adverse Events
timeFrame: Day 1 through Week 52
measure: Change from Baseline in Slow Vital Capacity at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in Sniff Nasal Inspiratory Pressure at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in Modified Norris Scale Score at Week 24
timeFrame: Baseline, Week 24
measure: Rate of Death
timeFrame: Baseline to Week 24
measure: Length of Time to Death
timeFrame: Baseline to Week 24
measure: Change from Baseline in ALS Assessment Questionnaire (ALSAQ-40) Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Neurofilament Light Chain (NfL) Activity at Week 24
timeFrame: Baseline, Week 24
measure: Area under the Concentration-time Curve (AUC) of PTC857 in Plasma
timeFrame: Predose through Week 24
measure: Maximum Observed Concentration (Cmax) of PTC857 in Plasma
timeFrame: Predose through Week 24
measure: AUC of PTC857 in Cerebrospinal Fluid (CSF)
timeFrame: Predose through Week 24
measure: Cmax of PTC857 in CSF
timeFrame: Predose through Week 24
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Health ALS and Neuromuscular Center
state: California
city: San Francisco
country: United States
facility: Forbes Norris MDA/ALS Research Center at California Pacific Medical Center
state: California
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital, Phil Smith Neuroscience Institute
state: Florida
city: Tampa
country: United States
facility: University of South Florida - Carol and Frank Morsani Center for Advanced Healthcare
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC) - Landon Center on Aging
state: Kansas
city: Detroit
country: United States
facility: Henry Ford Health System Department of Neurology
state: Michigan
city: Lincoln
country: United States
facility: Neurology Associates, P.C. / Somnos Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Portland
country: United States
facility: Providence Brain and Spine Institute
state: Oregon
city: Philadelphia
country: United States
facility: Lewis Katz School of Medicine at Temple Universtiy
state: Pennsylvania
city: Austin
country: United States
facility: National Neuromuscular Research Institute
state: Texas
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: STAT Research S.A.
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Iadin Srl.
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Ramos Mejía
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast Hospital
state: Queensland
city: Caulfield South
country: Australia
facility: Calvary Health Care Bethlehem
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Gent
country: Belgium
facility: AZ Sint-Lucas Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Brno
country: Czechia
facility: University hospital Brno, Department of Neurology
city: Prague 6
country: Czechia
facility: FORBELI s.r.o.
city: Bordeaux Cedex
country: France
facility: CHU de Bordeaux
city: Bron Cedex
country: France
facility: Hôpital Neurologique Pierre Wertheimer
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied
city: Lille Cedex
country: France
facility: CHRU Lille - Hôpital Roger Salengro
city: Limoges
country: France
facility: CHU Dupuytren 1 Limoges
city: Montpellier
country: France
facility: CHU Gui de Chauliac (Pharmacie Saint-Eloi & Gui de Chauliac, Hopital Saint-Eloi)
city: Nice
country: France
facility: CRMR SLA - MNM du CHU de Nice
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin - Berlin
city: Hannover
country: Germany
facility: Hannover Medical School
city: Jena
country: Germany
facility: University Hospital Jena
city: Lubeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein (UKSH) Campus Luebeck, Klinik fuer Neurologie, Praezisionsneurologie
city: Ulm
country: Germany
facility: University of Ulm, Dept. of Neurology
city: Brescia
country: Italy
facility: Centro Clinico Nemo Brescia
city: Milano
country: Italy
facility: Istituti Clinici Scientifici Maugeri IRCCS
city: Milano
country: Italy
facility: Istituto Auxolgoico Italiano
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria di Modena
city: Novara
country: Italy
facility: Maggiore della Carita University Hospital, Neurology department, ALS center
city: Palermo
country: Italy
facility: ALS Clinical Research Center, University Hospital Policlinico "P Giaccone"
city: Pavia
country: Italy
facility: IRCCS Fondazione Mondino - Reparto Neuroncologia/Neuroinfiammazione
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Torino
country: Italy
facility: AOU Citta Della Salute e Scienza
city: Japanese City
country: Japan
facility: PTC Clinical Site
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Warsaw
country: Poland
facility: City Clinic Research Sp. Z o.o
city: Warszawa
country: Poland
facility: Centrum Medyczne Neuro Protect
city: Barcelona
country: Spain
facility: Unidad Neuromuscular. Servicio de Neurologia Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: H. St Pau
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Malmo
country: Sweden
facility: Skanes universitetssjukhus, VE Neurologi
city: Umea
country: Sweden
facility: Norrlands universitetssjukhus Neurologens Forskningsavdelning
Study officials:
References: