The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05349721
Recruitment Status : Active, not recruiting
First Posted : April 27, 2022
Last Update Posted : March 15, 2024
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This study will assess the efficacy and safety of PTC857 treatment in participants diagnosed with ALS.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: PTC857 Drug: Placebo Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 258 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 15, 2022
Estimated Primary Completion Date : July 31, 2024
Estimated Study Completion Date : February 28, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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.

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

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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Change from Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) Score at Week 24 (Intention-to-Treat [ITT] 1 Analysis Population) [ Time Frame: 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.


Secondary Outcome Measures :
  1. Change from Baseline in ALSFRS-R Score at Week 24 (ITT2 Analysis Population) [ Time Frame: Baseline, Week 24 ]
    The ITT2 analysis population will include all participants who receive at least 1 dose of study drug.

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

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05349721


Locations
Show Show 55 study locations
Sponsors and Collaborators
PTC Therapeutics
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: PTC Therapeutics
ClinicalTrials.gov Identifier: NCT05349721    
Other Study ID Numbers: PTC857-CNS-001-ALS
First Posted: April 27, 2022    Key Record Dates
Last Update Posted: March 15, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
 Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases