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Safety and Biomarker Study of EPI-589 in Participants With Amyotrophic Lateral Sclerosis (ALS) (EPI-589)

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ClinicalTrials.gov Identifier: NCT02460679
Recruitment Status : Completed
First Posted : June 2, 2015
Results First Posted : September 23, 2020
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

Brief Summary:
This is an open label study with 30-day run in phase to establish baseline parameters, 90-day treatment phase, and a 90-day withdrawal phase to determine long-term effects, duration of treatment response, and potential effects of EPI-589 therapy on known trajectory.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: EPI-589 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2A Safety and Biomarker Study of EPI-589 in Subjects With Amyotrophic Lateral Sclerosis
Actual Study Start Date : January 14, 2016
Actual Primary Completion Date : February 23, 2018
Actual Study Completion Date : February 23, 2018


Arm Intervention/treatment
Experimental: EPI-589
Participants will receive EPI-589 500 milligrams (mg) (2 tablets of 250 mg each) twice daily (BID) for 3 months, unless discontinued for safety or tolerability issues.
Drug: EPI-589
An immediate release film-coated table at a 250 mg dosage strength will be administered per dose and schedule specified in arm.
Other Name: (R)-troloxamide quinone




Primary Outcome Measures :
  1. Number of Participants With Drug-Related Serious Adverse Events (SAEs) [ Time Frame: Baseline (Day 0) to Month 6 ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.


Secondary Outcome Measures :
  1. Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose at Month 1 and 3 ]
  2. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose at Month 1 and 3 ]
  3. Change From Baseline in ALSFRS-R Total Score at Month 6 [ Time Frame: Baseline, Month 6 ]
    ALSFRS-R is a quickly administered (5 minutes) ordinal rating scale that assesses participant's capability and independence in 12 functional activities. All 12 activities, 6 bulbar-respiratory functions, 3 upper extremity functions (writing, cutting food, and dressing), 2 lower-extremity functions (walking and climbing), and 1 other function (turning in bed), are relevant in ALS. Each activity was recorded to the closest approximation from a list of 5 choices, scored 0-4, with the total score ranging from 48 (normal function) to 0 (unable to attempt the task).

  4. Change From Baseline in Vital Capacity at Month 6 [ Time Frame: Baseline, Month 6 ]
    Vital capacity is the maximum amount of air a participant can expel from the lungs after a maximum inhalation.

  5. Change From Baseline in MIP at Month 6 [ Time Frame: Baseline, Month 6 ]
    MIP is a measure of the strength of inspiratory muscles, primarily the diaphragm, and allows for the assessment of ventilatory failure, restrictive lung disease, and respiratory muscle strength.

  6. Change From Baseline in Respiratory Rate at Month 6 [ Time Frame: Baseline, Month 6 ]
    Respiratory rate is the rate at which breathing occurs.

  7. Change From Baseline in Heart Rate at Month 6 [ Time Frame: Baseline, Month 6 ]
    The heart rate measures the number of times the heart beats per minute.

  8. Change From Baseline in SpO2 at Month 6 [ Time Frame: Baseline, Month 6 ]
    SpO2, also known as oxygen saturation, is a measure of the amount of oxygen-carrying hemoglobin in the blood relative to the amount of hemoglobin not carrying oxygen.

  9. Change From Baseline in ETCO2 at Month 6 [ Time Frame: Baseline, Month 6 ]
    ETCO2 is the amount of CO2 in exhaled air, which assesses ventilation.

  10. Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 6 [ Time Frame: Baseline, Month 6 ]
    The failure to thrive as measured by body weight was defined as weight loss of more than 5% from baseline

  11. Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6 [ Time Frame: Baseline, Month 6 ]
    Participants were observed and timed swallowing water as well as solid foods in accordance with a standardized protocol.

  12. Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion) [ Time Frame: Baseline, Month 6 ]
    The strength of designated muscle groups was measured using handheld dynamometry.

  13. Change From Baseline in Number of Words Participant Read at Month 6 [ Time Frame: Baseline, Month 6 ]
    The participant performed tasks in which speech was assessed through a perceptual assessment of overall intelligibility, vocal quality, and other factors by a speech language pathologist.

  14. Change From Baseline in Time Spent in Reading at Month 6 [ Time Frame: Baseline, Month 6 ]
    The participant performed tasks in which speech was assessed through a perceptual assessment of overall intelligibility, vocal quality, and other factors by a speech language pathologist.

  15. Change From Baseline in Number of Words Per Minute Read at Month 6 [ Time Frame: Baseline, Month 6 ]
    The participant performed tasks in which speech was assessed through a perceptual assessment of overall intelligibility, vocal quality, and other factors by a speech language pathologist.

  16. Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility [ Time Frame: Month 6 ]
    The participant performed tasks in which speech was assessed through a perceptual assessment of overall intelligibility, vocal quality, and other factors by a speech language pathologist.

  17. Level of Disease-Related Biomarker (Glutathione) in Plasma [ Time Frame: Baseline up to Month 6 ]
    Glutathione lowest limit of quantification (LLOQ) = 0.089 micromoles (uM) and upper limit of quantification (ULOQ) = 13.916 uM in plasma.

  18. Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF) [ Time Frame: Baseline up to Month 3 ]
    Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.

  19. Level of Disease-Related Biomarker (Glutathione) in Urine [ Time Frame: Baseline up to Month 6 ]
    Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.



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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of possible, probable, laboratory supported probable, or definite ALS by E1 Escorial Criteria
  • Forced vital capacity (FVC) ≥ 70% of predicted
  • Weakness onset within 3 years
  • Agreement to use contraception if within reproductive years
  • Willingness and ability to comply with study procedures
  • Stable regimen of dietary supplements and /or riluzole for at least 30 days prior to enrollment
  • Abstention from use of other investigative or non-approved drugs
  • Participants must be able to swallow 0.375 * 0.700 inch tablets

Exclusion Criteria:

  • Allergy to EPI-589
  • Use of ventilation
  • Participation in other intervention studies
  • Diagnosis of any other neurologic disease
  • Malignancy within the past 2 years
  • History of stroke
  • History of brain surgery
  • Hepatic insufficiency with liver function tests (LFTs) greater than 3 times upper limit of normal (ULN)
  • Renal insufficiency requiring dialysis
  • End stage cardiac failure
  • Participation in a trial of a device, drug, or other therapy for ALS within 3 months of screening or during the trial

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): NCT02460679


Locations
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United States, California
Cedar's Sinai
Los Angeles, California, United States, 90048
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Oregon
Providence Brain and Spine Institute ALS Center
Portland, Oregon, United States, 97213
Sponsors and Collaborators
PTC Therapeutics
Investigators
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Study Director: Matthew B Klein, MD, FACS PTC Therapeutics
  Study Documents (Full-Text)

Documents provided by PTC Therapeutics:
Study Protocol  [PDF] February 17, 2017
Statistical Analysis Plan  [PDF] March 20, 2018

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Responsible Party: PTC Therapeutics
ClinicalTrials.gov Identifier: NCT02460679    
Other Study ID Numbers: EPI589-15-001
First Posted: June 2, 2015    Key Record Dates
Results First Posted: September 23, 2020
Last Update Posted: October 14, 2020
Last Verified: September 2020
Additional relevant MeSH terms:
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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