Clinical trial NCT02460679: Safety and Biomarker Study of EPI-589 in Participants With Amyotrophic Lateral Sclerosis (ALS)
Official title: A Phase 2A Safety and Biomarker Study of EPI-589 in Subjects With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-06-02
Enrollment: 19
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Drug-Related Serious Adverse Events (SAEs)
timeFrame: Baseline (Day 0) to Month 6
Secondary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12)
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose at Month 1 and 3
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose at Month 1 and 3
measure: Change From Baseline in ALSFRS-R Total Score at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Vital Capacity at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in MIP at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Respiratory Rate at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Heart Rate at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in SpO2 at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in ETCO2 at Month 6
timeFrame: Baseline, Month 6
measure: Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6
timeFrame: Baseline, Month 6
measure: 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)
timeFrame: Baseline, Month 6
measure: Change From Baseline in Number of Words Participant Read at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Time Spent in Reading at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Number of Words Per Minute Read at Month 6
timeFrame: Baseline, Month 6
measure: Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility
timeFrame: Month 6
measure: Level of Disease-Related Biomarker (Glutathione) in Plasma
timeFrame: Baseline up to Month 6
measure: Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
timeFrame: Baseline up to Month 3
measure: Level of Disease-Related Biomarker (Glutathione) in Urine
timeFrame: Baseline up to Month 6
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedar's Sinai
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Portland
country: United States
facility: Providence Brain and Spine Institute ALS Center
state: Oregon
Study officials:
affiliation: PTC Therapeutics
name: Matthew B Klein, MD, FACS
role: STUDY_DIRECTOR
References: