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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PTC857
Placebo
Sponsored by
PTC Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Males or females aged between 18 and 70 years with a body mass index between 18 and 35 kilograms/meters squared
  • ALS with preserved function, defined as:

    1. Onset of the first symptom leading to the diagnosis of ALS ≥7 and ≤18 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%
  • All concomitant medications (both prescription and over the counter) and non-pharmacologic therapy regimens should be stable and unchanged from 30 days prior to the start of the Screening Period and intend to remain stable and unchanged throughout the course of the study, with the exception of prohibited medications
  • 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.

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
  • Edaravone 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

Sites / Locations

  • UC Irvine Health ALS and Neuromuscular CenterRecruiting
  • Forbes Norris MDA/ALS Research Center at California Pacific Medical CenterRecruiting
  • Holy Cross Hospital, Phil Smith Neuroscience Institute
  • University of South Florida - Carol and Frank Morsani Center for Advanced HealthcareRecruiting
  • Augusta UniversityRecruiting
  • University of Kansas Medical Center (KUMC) - Landon Center on Aging
  • Henry Ford Health System Department of Neurology
  • Neurology Associates, P.C. / Somnos Clinical ResearchRecruiting
  • University of Nebraska Medical CenterRecruiting
  • Providence Brain and Spine Institute
  • Lewis Katz School of Medicine at Temple Universtiy
  • National Neuromuscular Research InstituteRecruiting
  • Nerve and Muscle Center of TexasRecruiting
  • Iadin Srl.Recruiting
  • Royal Brisbane and Women's HospitalRecruiting
  • Gold Coast HospitalRecruiting
  • Calvary Health Care Bethlehem
  • Austin HealthRecruiting
  • AZ Sint-Lucas Gent
  • UZ LeuvenRecruiting
  • FORBELI s.r.o.Recruiting
  • CHU de BordeauxRecruiting
  • Hôpital Neurologique Pierre WertheimerRecruiting
  • CHRU Lille - Hôpital Roger SalengroRecruiting
  • CHU Dupuytren 1 LimogesRecruiting
  • CRMR SLA - MNM du CHU de Nice
  • Hannover Medical SchoolRecruiting
  • Universitaetsklinikum Schleswig-Holstein (UKSH) Campus Luebeck, Klinik fuer Neurologie, PraezisionsneurologieRecruiting
  • Centro Clinico Nemo Brescia
  • Istituti Clinici Scientifici Maugeri IRCCSRecruiting
  • Istituto Auxolgoico ItalianoRecruiting
  • Maggiore della Carita University Hospital, Neurology department, ALS centerRecruiting
  • ALS Clinical Research Center, University Hospital Policlinico "P Giaccone"
  • Policlinico Umberto I
  • AOU Citta Della Salute e ScienzaRecruiting
  • UMC UtrechtRecruiting
  • City Clinic Research Sp. Z o.oRecruiting
  • Centrum Medyczne Neuro ProtectRecruiting
  • Unidad Neuromuscular. Servicio de Neurologia Hospital Universitari Vall d'HebronRecruiting
  • H. St Pau
  • Hospital Universitario y Politecnico La FeRecruiting
  • Skanes universitetssjukhus, VE Neurologi

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

PTC857

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Number of Participants with Treatment-emergent Adverse Events
Change from Baseline in Slow Vital Capacity at Week 24
Change from Baseline in Sniff Nasal Inspiratory Pressure at Week 24
Change from Baseline in Modified Norris Scale Score at Week 24
Change from Baseline in ALS Cognitive Behavioral Screen Assessment at Week 24
Rate of Needing Respiratory Support/Intubation and/or Death
Length of Time to Needing Respiratory Support/Intubation and/or Death
Combined Assessment of Function and Survival (CAFS) Score
Change from Baseline in ALS Assessment Questionnaire (ALSAQ-40) Score at Week 24
Area under the Concentration-time Curve (AUC) of PTC857 in Plasma
Maximum Observed Concentration (Cmax) of PTC857 in Plasma
AUC of PTC857 in Cerebrospinal Fluid (CSF)
Cmax of PTC857 in CSF

Full Information

First Posted
April 21, 2022
Last Updated
October 11, 2023
Sponsor
PTC Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05349721
Brief Title
Study to Assess the Effects of PTC857 Treatment in Participants With Amyotrophic Lateral Sclerosis ALS
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 15, 2022 (Actual)
Primary Completion Date
July 31, 2024 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PTC Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
258 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PTC857
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PTC857
Intervention Description
PTC8657 will be administered as an oral solution twice a day.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo will be administered as an oral solution twice a day.
Primary Outcome Measure Information:
Title
Change from Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) Score at Week 24 (Intention-to-Treat [ITT] 1 Analysis Population)
Description
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.
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Change from Baseline in ALSFRS-R Score at Week 24 (ITT2 Analysis Population)
Description
The ITT2 analysis population will include all participants who receive at least 1 dose of study drug.
Time Frame
Baseline, Week 24
Title
Number of Participants with Treatment-emergent Adverse Events
Time Frame
Day 1 through Week 52
Title
Change from Baseline in Slow Vital Capacity at Week 24
Time Frame
Baseline, Week 24
Title
Change from Baseline in Sniff Nasal Inspiratory Pressure at Week 24
Time Frame
Baseline, Week 24
Title
Change from Baseline in Modified Norris Scale Score at Week 24
Time Frame
Baseline, Week 24
Title
Change from Baseline in ALS Cognitive Behavioral Screen Assessment at Week 24
Time Frame
Baseline, Week 24
Title
Rate of Needing Respiratory Support/Intubation and/or Death
Time Frame
Baseline, Week 24
Title
Length of Time to Needing Respiratory Support/Intubation and/or Death
Time Frame
Baseline, Week 24
Title
Combined Assessment of Function and Survival (CAFS) Score
Time Frame
Week 24
Title
Change from Baseline in ALS Assessment Questionnaire (ALSAQ-40) Score at Week 24
Time Frame
Baseline, Week 24
Title
Area under the Concentration-time Curve (AUC) of PTC857 in Plasma
Time Frame
Predose through Week 24
Title
Maximum Observed Concentration (Cmax) of PTC857 in Plasma
Time Frame
Predose through Week 24
Title
AUC of PTC857 in Cerebrospinal Fluid (CSF)
Time Frame
Predose through Week 24
Title
Cmax of PTC857 in CSF
Time Frame
Predose through Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: 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. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Patient Advocacy
Phone
1-866-562-4620
Email
medinfo@ptcbio.com
Facility Information:
Facility Name
UC Irvine Health ALS and Neuromuscular Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
Forbes Norris MDA/ALS Research Center at California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Individual Site Status
Recruiting
Facility Name
Holy Cross Hospital, Phil Smith Neuroscience Institute
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of South Florida - Carol and Frank Morsani Center for Advanced Healthcare
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Kansas Medical Center (KUMC) - Landon Center on Aging
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Henry Ford Health System Department of Neurology
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Neurology Associates, P.C. / Somnos Clinical Research
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68506
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-8440
Country
United States
Individual Site Status
Recruiting
Facility Name
Providence Brain and Spine Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Lewis Katz School of Medicine at Temple Universtiy
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
National Neuromuscular Research Institute
City
Austin
State/Province
Texas
ZIP/Postal Code
78759
Country
United States
Individual Site Status
Recruiting
Facility Name
Nerve and Muscle Center of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Iadin Srl.
City
Buenos Aires
ZIP/Postal Code
C1015ABR
Country
Argentina
Individual Site Status
Recruiting
Facility Name
Royal Brisbane and Women's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Individual Site Status
Recruiting
Facility Name
Gold Coast Hospital
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Individual Site Status
Recruiting
Facility Name
Calvary Health Care Bethlehem
City
Caulfield South
State/Province
Victoria
ZIP/Postal Code
3162
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Name
AZ Sint-Lucas Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
FORBELI s.r.o.
City
Prague 6
ZIP/Postal Code
160 00
Country
Czechia
Individual Site Status
Recruiting
Facility Name
CHU de Bordeaux
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital Neurologique Pierre Wertheimer
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Individual Site Status
Recruiting
Facility Name
CHRU Lille - Hôpital Roger Salengro
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Dupuytren 1 Limoges
City
Limoges
ZIP/Postal Code
87000
Country
France
Individual Site Status
Recruiting
Facility Name
CRMR SLA - MNM du CHU de Nice
City
Nice
ZIP/Postal Code
06200
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Hannover Medical School
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitaetsklinikum Schleswig-Holstein (UKSH) Campus Luebeck, Klinik fuer Neurologie, Praezisionsneurologie
City
Lubeck
ZIP/Postal Code
23538
Country
Germany
Individual Site Status
Recruiting
Facility Name
Centro Clinico Nemo Brescia
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Individual Site Status
Not yet recruiting
Facility Name
Istituti Clinici Scientifici Maugeri IRCCS
City
Milano
ZIP/Postal Code
20138
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Auxolgoico Italiano
City
Milano
ZIP/Postal Code
20149
Country
Italy
Individual Site Status
Recruiting
Facility Name
Maggiore della Carita University Hospital, Neurology department, ALS center
City
Novara
ZIP/Postal Code
28100
Country
Italy
Individual Site Status
Recruiting
Facility Name
ALS Clinical Research Center, University Hospital Policlinico "P Giaccone"
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Individual Site Status
Not yet recruiting
Facility Name
Policlinico Umberto I
City
Roma
ZIP/Postal Code
00161
Country
Italy
Individual Site Status
Not yet recruiting
Facility Name
AOU Citta Della Salute e Scienza
City
Torino
ZIP/Postal Code
10126
Country
Italy
Individual Site Status
Recruiting
Facility Name
UMC Utrecht
City
Utrecht
ZIP/Postal Code
3584 CW
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
City Clinic Research Sp. Z o.o
City
Warsaw
ZIP/Postal Code
02-473
Country
Poland
Individual Site Status
Recruiting
Facility Name
Centrum Medyczne Neuro Protect
City
Warszawa
ZIP/Postal Code
01-684
Country
Poland
Individual Site Status
Recruiting
Facility Name
Unidad Neuromuscular. Servicio de Neurologia Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
H. St Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Hospital Universitario y Politecnico La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Name
Skanes universitetssjukhus, VE Neurologi
City
Malmo
ZIP/Postal Code
SE-211 24
Country
Sweden
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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