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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05349721




Registration number
NCT05349721
Ethics application status
Date submitted
21/04/2022
Date registered
27/04/2022

Titles & IDs
Public title
Study to Assess the Effects of PTC857 Treatment in Participants With Amyotrophic Lateral Sclerosis ALS
Scientific 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)
Secondary ID [1] 0 0
PTC857-CNS-001-ALS
Universal Trial Number (UTN)
Trial acronym
CARDINALS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PTC857
Treatment: Drugs - Placebo

Experimental: 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.

Active comparator: 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.


Treatment: Drugs: PTC857
PTC8657 will be administered as an oral solution twice a day.

Treatment: Drugs: Placebo
Matching placebo will be administered as an oral solution twice a day.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) Score at Week 24 (Intention-to-Treat [ITT] 1 Analysis Population)
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Change from Baseline in ALSFRS-R Score at Week 24 (ITT2 Analysis Population)
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Number of Participants with Treatment-emergent Adverse Events
Timepoint [2] 0 0
Day 1 through Week 52
Secondary outcome [3] 0 0
Change from Baseline in Slow Vital Capacity at Week 24
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Change from Baseline in Sniff Nasal Inspiratory Pressure at Week 24
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Change from Baseline in Modified Norris Scale Score at Week 24
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Change from Baseline in ALS Cognitive Behavioral Screen Assessment at Week 24
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Rate of Needing Respiratory Support/Intubation and/or Death
Timepoint [7] 0 0
Baseline, Week 24
Secondary outcome [8] 0 0
Length of Time to Needing Respiratory Support/Intubation and/or Death
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Combined Assessment of Function and Survival (CAFS) Score
Timepoint [9] 0 0
Week 24
Secondary outcome [10] 0 0
Change from Baseline in ALS Assessment Questionnaire (ALSAQ-40) Score at Week 24
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Area under the Concentration-time Curve (AUC) of PTC857 in Plasma
Timepoint [11] 0 0
Predose through Week 24
Secondary outcome [12] 0 0
Maximum Observed Concentration (Cmax) of PTC857 in Plasma
Timepoint [12] 0 0
Predose through Week 24
Secondary outcome [13] 0 0
AUC of PTC857 in Cerebrospinal Fluid (CSF)
Timepoint [13] 0 0
Predose through Week 24
Secondary outcome [14] 0 0
Cmax of PTC857 in CSF
Timepoint [14] 0 0
Predose through Week 24

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/02/2025
Actual
Sample size
Target
Accrual to date
Final
258
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [2] 0 0
Gold Coast Hospital - Southport
Recruitment hospital [3] 0 0
Calvary Health Care Bethlehem - Caulfield South
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
3162 - Caulfield South
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Wisconsin
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Argentina
State/province [12] 0 0
Ciudad Autonoma de Buenos Aires
Country [13] 0 0
Belgium
State/province [13] 0 0
Gent
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Czechia
State/province [15] 0 0
Brno
Country [16] 0 0
Czechia
State/province [16] 0 0
Prague 6
Country [17] 0 0
France
State/province [17] 0 0
Bordeaux Cedex
Country [18] 0 0
France
State/province [18] 0 0
Bron Cedex
Country [19] 0 0
France
State/province [19] 0 0
Clermont-Ferrand
Country [20] 0 0
France
State/province [20] 0 0
Lille Cedex
Country [21] 0 0
France
State/province [21] 0 0
Limoges
Country [22] 0 0
France
State/province [22] 0 0
Montpellier
Country [23] 0 0
France
State/province [23] 0 0
Nice
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Germany
State/province [25] 0 0
Hannover
Country [26] 0 0
Germany
State/province [26] 0 0
Jena
Country [27] 0 0
Germany
State/province [27] 0 0
Lubeck
Country [28] 0 0
Germany
State/province [28] 0 0
Ulm
Country [29] 0 0
Italy
State/province [29] 0 0
Brescia
Country [30] 0 0
Italy
State/province [30] 0 0
Milano
Country [31] 0 0
Italy
State/province [31] 0 0
Modena
Country [32] 0 0
Italy
State/province [32] 0 0
Novara
Country [33] 0 0
Italy
State/province [33] 0 0
Palermo
Country [34] 0 0
Italy
State/province [34] 0 0
Pavia
Country [35] 0 0
Italy
State/province [35] 0 0
Roma
Country [36] 0 0
Italy
State/province [36] 0 0
Torino
Country [37] 0 0
Japan
State/province [37] 0 0
Japanese City
Country [38] 0 0
Netherlands
State/province [38] 0 0
Utrecht
Country [39] 0 0
Poland
State/province [39] 0 0
Warsaw
Country [40] 0 0
Poland
State/province [40] 0 0
Warszawa
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Valencia
Country [43] 0 0
Sweden
State/province [43] 0 0
Malmo
Country [44] 0 0
Sweden
State/province [44] 0 0
Umea

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
PTC Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05349721