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CompletedNCT02460679EPI-589Updated Oct 14, 2020Results posted

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

A Phase 2 interventional study of EPI-589 in Amyotrophic Lateral Sclerosis, sponsored by PTC Therapeutics. Completed at 3 sites in United States. Open to participants aged 21 Years to 70 Years. Per ClinicalTrials.gov, last updated 2020-10-14.

Sponsored by PTC Therapeutics · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
19
Allocation
Not applicable
Ages
21 Years to 70 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Amyotrophic Lateral Sclerosis
03

In context

Motor Neuron Disease

717 studies on the registry are indexed under Motor Neuron Disease; 137 are open to participants now.

This study's enrollment of 19 is below the median of 35 across 461 interventional studies indexed under Motor Neuron Disease.

Browse Motor Neuron Disease studies →

Lead sponsor

PTC Therapeutics is the lead sponsor of 65 studies on the registry; 3 are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 14 (78%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
19 participants (actual)

Study arms

  • 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

Interventions

  • DrugEPI-589

    An immediate release film-coated table at a 250 mg dosage strength will be administered per dose and schedule specified in arm.

    Also known as: (R)-troloxamide quinone

06

What researchers measure

Primary outcomes

  1. 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'.

    Time frame: Baseline (Day 0) to Month 6

Secondary outcomes

  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

    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

  4. 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.

    Time frame: Baseline, Month 6

  5. 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.

    Time frame: Baseline, Month 6

  6. Change From Baseline in Respiratory Rate at Month 6

    Respiratory rate is the rate at which breathing occurs.

    Time frame: Baseline, Month 6

  7. Change From Baseline in Heart Rate at Month 6

    The heart rate measures the number of times the heart beats per minute.

    Time frame: Baseline, Month 6

  8. 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.

    Time frame: Baseline, Month 6

  9. Change From Baseline in ETCO2 at Month 6

    ETCO2 is the amount of CO2 in exhaled air, which assesses ventilation.

    Time frame: Baseline, Month 6

  10. 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

    Time frame: Baseline, Month 6

  11. 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.

    Time frame: Baseline, Month 6

  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)

    The strength of designated muscle groups was measured using handheld dynamometry.

    Time frame: Baseline, Month 6

  13. 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.

    Time frame: Baseline, Month 6

  14. 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.

    Time frame: Baseline, Month 6

  15. 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.

    Time frame: Baseline, Month 6

  16. 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.

    Time frame: Month 6

  17. 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.

    Time frame: Baseline up to Month 6

  18. Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)

    Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.

    Time frame: Baseline up to Month 3

  19. Level of Disease-Related Biomarker (Glutathione) in Urine

    Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.

    Time frame: Baseline up to Month 6

07

Results

Posted Sep 23, 2020

Participant flow

Participant flow — Overall Study
MilestoneEPI-589
Started19
Received at least 1 dose of study drug19
Completed14
Not completed5
Withdrew: Investigator decision1
Withdrew: Withdrawal by subject4

Outcome measures

PrimaryNumber 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'.

Time frame:
Baseline (Day 0) to Month 6
Reported as:
Count of participants · Participants
Number of Participants With Drug-Related Serious Adverse Events (SAEs)
ParticipantsEPI-589
Number of Participants With Drug-Related Serious Adverse Events (SAEs)0
SecondaryArea 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
Reported as:
Mean · hours*nanograms/milliliter
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12)
hours*nanograms/milliliterEPI-589
Month 17762.7 ± 721.1
Month 36878.8 ± 401.1
SecondaryMaximum 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
Reported as:
Mean · ng/mL
Maximum Observed Plasma Concentration (Cmax)
ng/mLEPI-589
Month 15179.0 ± 930.3
Month 34167.8 ± 642.2
SecondaryChange 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).

Time frame:
Baseline, Month 6
Reported as:
Mean · units on a scale
Change From Baseline in ALSFRS-R Total Score at Month 6
units on a scaleEPI-589
Change From Baseline in ALSFRS-R Total Score at Month 6-4.1 ± 4.03
SecondaryChange 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.

Time frame:
Baseline, Month 6
Reported as:
Mean · percentage of capacity
Change From Baseline in Vital Capacity at Month 6
percentage of capacityEPI-589
Change From Baseline in Vital Capacity at Month 6-3.1 ± 9.36
SecondaryChange 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.

Time frame:
Baseline, Month 6
Reported as:
Mean · cm H2O
Change From Baseline in MIP at Month 6
cm H2OEPI-589
Change From Baseline in MIP at Month 62.4 ± 24.83
SecondaryChange From Baseline in Respiratory Rate at Month 6

Respiratory rate is the rate at which breathing occurs.

Time frame:
Baseline, Month 6
Reported as:
Mean · breaths/minute
Change From Baseline in Respiratory Rate at Month 6
breaths/minuteEPI-589
Sitting0.3 ± 3.45
After 5 minutes supine-0.6 ± 5.57
After 10 minutes supine0.0 ± 4.32
SecondaryChange From Baseline in Heart Rate at Month 6

The heart rate measures the number of times the heart beats per minute.

Time frame:
Baseline, Month 6
Reported as:
Mean · beats/minute
Change From Baseline in Heart Rate at Month 6
beats/minuteEPI-589
Sitting5.2 ± 10.74
After 5 minutes supine7.1 ± 7.49
After 10 minutes supine7.2 ± 8.39
SecondaryChange 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.

Time frame:
Baseline, Month 6
Reported as:
Mean · percentage of hemoglobin
Change From Baseline in SpO2 at Month 6
percentage of hemoglobinEPI-589
Sitting-1.0 ± 1.71
After 5 minutes supine-0.8 ± 4.64
After 10 minutes supine-0.1 ± 3.55
SecondaryChange From Baseline in ETCO2 at Month 6

ETCO2 is the amount of CO2 in exhaled air, which assesses ventilation.

Time frame:
Baseline, Month 6
Reported as:
Mean · percentage of CO2
Change From Baseline in ETCO2 at Month 6
percentage of CO2EPI-589
Sitting2.384 ± 8.2343
After 5 minutes supine0.605 ± 5.0262
After 10 minutes supine7.112 ± 9.6591
SecondaryFailure 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

Time frame:
Baseline, Month 6
Reported as:
Count of participants · Participants
Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 6
ParticipantsEPI-589
Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 62
SecondaryChange 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.

Time frame:
Baseline, Month 6
Reported as:
Mean · seconds
Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6
secondsEPI-589
Average Solid Swallowing Time4.80 ± 11.718
Average Water Swallowing Time6.65 ± 20.950
SecondaryChange 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.

Time frame:
Baseline, Month 6
Reported as:
Mean · kilograms
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)
kilogramsEPI-589
Grip - Left-9.69 ± 15.330
Grip - Right-7.28 ± 7.207
Shoulder Flexion - Left-4.53 ± 6.922
Shoulder Flexion - Right-5.43 ± 8.915
Knee Extension - Left-5.42 ± 10.254
Knee Extension - Right-5.05 ± 11.505
Knee Flexion - Left-4.63 ± 8.237
Knee Flexion - Right-4.01 ± 9.170
Hip Flexion - Left-6.84 ± 12.579
Hip Flexion - Right-5.60 ± 9.627
Elbow Flexion - Left-4.84 ± 8.377
Elbow Flexion - Right-3.28 ± 8.186
Elbow Extension - Left-5.77 ± 10.511
Elbow Extension - Right-4.28 ± 9.048
Ankle Dorsi Flexion - Left-6.12 ± 7.609
Ankle Dorsi Flexion - Right-4.89 ± 7.529
SecondaryChange 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.

Time frame:
Baseline, Month 6
Reported as:
Mean · words
Change From Baseline in Number of Words Participant Read at Month 6
wordsEPI-589
Change From Baseline in Number of Words Participant Read at Month 60.0 ± 0.00
SecondaryChange 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.

Time frame:
Baseline, Month 6
Reported as:
Mean · seconds
Change From Baseline in Time Spent in Reading at Month 6
secondsEPI-589
Change From Baseline in Time Spent in Reading at Month 65.5 ± 11.78
SecondaryChange 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.

Time frame:
Baseline, Month 6
Reported as:
Mean · words/minute
Change From Baseline in Number of Words Per Minute Read at Month 6
words/minuteEPI-589
Change From Baseline in Number of Words Per Minute Read at Month 6-147.535 ± 26.7792
SecondaryNumber 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.

Time frame:
Month 6
Reported as:
Count of participants · Participants
Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility
ParticipantsEPI-589
Normal Loudness10
Normal Nasality6
Normal Intelligibility6
SecondaryLevel 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.

Time frame:
Baseline up to Month 6
Reported as:
Mean · µM
Level of Disease-Related Biomarker (Glutathione) in Plasma
µMEPI-589
Baseline1.34 (0.41 to 2.15)
Month 62.73 (0.83 to 11.74)
SecondaryLevel of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)

Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.

Time frame:
Baseline up to Month 3
Reported as:
Mean · µM
Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
µMEPI-589
Baseline0.13 (0.04 to 0.31)
Month 30.13 (0.06 to 0.31)
SecondaryLevel of Disease-Related Biomarker (Glutathione) in Urine

Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.

Time frame:
Baseline up to Month 6
Reported as:
Mean · µM
Level of Disease-Related Biomarker (Glutathione) in Urine
µMEPI-589
Baseline0.12 (0.03 to 0.46)
Month 60.17 (0.02 to 0.82)

Adverse events

Collected over Baseline (Day 0) to Month 6. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
EPI-5890/19 (0%)0/19 (0%)15/19 (78.9%)
Most frequent other events
Showing 10 of 51
Most frequent other events
EventEPI-589
NauseaGastrointestinal disorders6/19
FallInjury, poisoning and procedural complications5/19
Back painMusculoskeletal and connective tissue disorders4/19
Oropharyngeal painRespiratory, thoracic and mediastinal disorders4/19
NasopharyngitisInfections and infestations3/19
Decreased appetiteMetabolism and nutrition disorders3/19
HeadacheNervous system disorders3/19
DiarrhoeaGastrointestinal disorders2/19
ChillsGeneral disorders2/19
ContusionInjury, poisoning and procedural complications2/19

Baseline characteristics

Efficacy intent-to-treat (EITT) population or safety population included any participant who received at least 1 dose of EPI-589.

Age, Continuous
Age, Continuous(years)EPI-589
Mean55.9 ± 8.25
Sex: Female, Male
Sex: Female, Male(Participants)EPI-589
Female5
Male14
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)EPI-589
Hispanic or Latino2
Not Hispanic or Latino17
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)EPI-589
American Indian or Alaska Native0
Asian1
Native Hawaiian or Other Pacific Islander0
Black or African American1
White17
More than one race0
Unknown or Not Reported0
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score(units on a scale)EPI-589
Mean37.4 ± 6.19
Vital Capacity
Vital Capacity(percentage of capacity)EPI-589
Mean97.7 ± 18.14
Maximum Inspiratory Pressure (MIP)
Maximum Inspiratory Pressure (MIP)(centimetres of water at (cm H2O))EPI-589
Mean68.2 ± 34.53
Respiratory Rate
Respiratory Rate(breaths/minute)EPI-589
Sitting15.1 ± 3.32
After 5 minutes supine14.7 ± 3.71
After 10 minutes supine14.7 ± 3.28

9 further baseline measures are reported on the registry.

08

Study locations

3 sites
  • Cedar's Sinai
    Los Angeles, California 90048, United States
  • California Pacific Medical Center
    San Francisco, California 94115, United States
  • Providence Brain and Spine Institute ALS Center
    Portland, Oregon 97213, United States
09

References and documents

Study documents

  • Study protocol · Feb 17, 2017
  • Statistical analysis plan · Mar 20, 2018

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 14, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02460679
Lead sponsor
PTC Therapeutics
Responsible party
Sponsor
First posted
Jun 2, 2015
Start date
Jan 14, 2016
Primary completion
Feb 23, 2018
Completion
Feb 23, 2018
Results posted
Sep 23, 2020
Last update
Oct 14, 2020

Study contacts

Matthew B Klein, MD, FACS
study director · PTC Therapeutics

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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