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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
EPI-589
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

21 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cedar's Sinai
  • California Pacific Medical Center
  • Providence Brain and Spine Institute ALS Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EPI-589

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Participants With Drug-Related Serious Adverse Events (SAEs)
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

Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12)
Maximum Observed Plasma Concentration (Cmax)
Change From Baseline in ALSFRS-R Total Score at 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).
Change From Baseline in Vital Capacity at Month 6
Vital capacity is the maximum amount of air a participant can expel from the lungs after a maximum inhalation.
Change From Baseline in MIP at 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.
Change From Baseline in Respiratory Rate at Month 6
Respiratory rate is the rate at which breathing occurs.
Change From Baseline in Heart Rate at Month 6
The heart rate measures the number of times the heart beats per minute.
Change From Baseline in SpO2 at 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.
Change From Baseline in ETCO2 at Month 6
ETCO2 is the amount of CO2 in exhaled air, which assesses ventilation.
Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 6
The failure to thrive as measured by body weight was defined as weight loss of more than 5% from baseline
Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6
Participants were observed and timed swallowing water as well as solid foods in accordance with a standardized protocol.
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)
The strength of designated muscle groups was measured using handheld dynamometry.
Change From Baseline in Number of Words Participant Read at 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.
Change From Baseline in Time Spent in Reading at 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.
Change From Baseline in Number of Words Per Minute Read at 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.
Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility
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.
Level of Disease-Related Biomarker (Glutathione) in Plasma
Glutathione lowest limit of quantification (LLOQ) = 0.089 micromoles (uM) and upper limit of quantification (ULOQ) = 13.916 uM in plasma.
Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.
Level of Disease-Related Biomarker (Glutathione) in Urine
Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.

Full Information

First Posted
May 21, 2015
Last Updated
September 23, 2020
Sponsor
PTC Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT02460679
Brief Title
Safety and Biomarker Study of EPI-589 in Participants With Amyotrophic Lateral Sclerosis (ALS)
Acronym
EPI-589
Official Title
A Phase 2A Safety and Biomarker Study of EPI-589 in Subjects With Amyotrophic Lateral Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
January 14, 2016 (Actual)
Primary Completion Date
February 23, 2018 (Actual)
Study Completion Date
February 23, 2018 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

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
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EPI-589
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
EPI-589
Other Intervention Name(s)
(R)-troloxamide quinone
Intervention Description
An immediate release film-coated table at a 250 mg dosage strength will be administered per dose and schedule specified in arm.
Primary Outcome Measure Information:
Title
Number of Participants With Drug-Related Serious Adverse Events (SAEs)
Description
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'.
Time Frame
Baseline (Day 0) to Month 6
Secondary Outcome Measure Information:
Title
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
Title
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
Title
Change From Baseline in ALSFRS-R Total Score at Month 6
Description
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).
Time Frame
Baseline, Month 6
Title
Change From Baseline in Vital Capacity at Month 6
Description
Vital capacity is the maximum amount of air a participant can expel from the lungs after a maximum inhalation.
Time Frame
Baseline, Month 6
Title
Change From Baseline in MIP at Month 6
Description
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.
Time Frame
Baseline, Month 6
Title
Change From Baseline in Respiratory Rate at Month 6
Description
Respiratory rate is the rate at which breathing occurs.
Time Frame
Baseline, Month 6
Title
Change From Baseline in Heart Rate at Month 6
Description
The heart rate measures the number of times the heart beats per minute.
Time Frame
Baseline, Month 6
Title
Change From Baseline in SpO2 at Month 6
Description
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.
Time Frame
Baseline, Month 6
Title
Change From Baseline in ETCO2 at Month 6
Description
ETCO2 is the amount of CO2 in exhaled air, which assesses ventilation.
Time Frame
Baseline, Month 6
Title
Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 6
Description
The failure to thrive as measured by body weight was defined as weight loss of more than 5% from baseline
Time Frame
Baseline, Month 6
Title
Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6
Description
Participants were observed and timed swallowing water as well as solid foods in accordance with a standardized protocol.
Time Frame
Baseline, Month 6
Title
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)
Description
The strength of designated muscle groups was measured using handheld dynamometry.
Time Frame
Baseline, Month 6
Title
Change From Baseline in Number of Words Participant Read at Month 6
Description
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.
Time Frame
Baseline, Month 6
Title
Change From Baseline in Time Spent in Reading at Month 6
Description
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.
Time Frame
Baseline, Month 6
Title
Change From Baseline in Number of Words Per Minute Read at Month 6
Description
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.
Time Frame
Baseline, Month 6
Title
Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility
Description
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.
Time Frame
Month 6
Title
Level of Disease-Related Biomarker (Glutathione) in Plasma
Description
Glutathione lowest limit of quantification (LLOQ) = 0.089 micromoles (uM) and upper limit of quantification (ULOQ) = 13.916 uM in plasma.
Time Frame
Baseline up to Month 6
Title
Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
Description
Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.
Time Frame
Baseline up to Month 3
Title
Level of Disease-Related Biomarker (Glutathione) in Urine
Description
Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.
Time Frame
Baseline up to Month 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew B Klein, MD, FACS
Organizational Affiliation
PTC Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Cedar's Sinai
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Providence Brain and Spine Institute ALS Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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