Amyotrophic Lateral SclerosisPhase 2EPI-589NCT02460679
Safety and Biomarker Study of EPI-589 in Participants With Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing EPI-589 in people with Amyotrophic Lateral Sclerosis, run by PTC Therapeutics at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- EPI-589
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 3 sitesUnited States
- Study dates
- 14 Jan 2016to 23 Feb 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cedar's Sinai
Los Angeles, California, 90048
Providence Brain and Spine Institute ALS Center
Portland, Oregon, 97213
California Pacific Medical Center
San Francisco, California, 94115
About this study
Official title: A Phase 2A Safety and Biomarker Study of EPI-589 in Subjects With Amyotrophic Lateral Sclerosis
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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- EPI-589
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EPI-589Drug
Also called (R)-troloxamide quinone
An immediate release film-coated table at a 250 mg dosage strength will be administered per dose and schedule specified in arm.
| Study group | Role | What they receive |
|---|---|---|
| EPI-589 | Experimental | 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. Receives: Drug: EPI-589 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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'.
Measured: Baseline (Day 0) to Month 6
Secondary outcomes (19)
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12)
Measured: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose at Month 1 and 3
Maximum Observed Plasma Concentration (Cmax)
Measured: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose at Month 1 and 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).
Measured: Baseline, Month 6
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.
Measured: Baseline, Month 6
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.
Measured: Baseline, Month 6
Change From Baseline in Respiratory Rate at Month 6
Respiratory rate is the rate at which breathing occurs.
Measured: Baseline, Month 6
Change From Baseline in Heart Rate at Month 6
The heart rate measures the number of times the heart beats per minute.
Measured: Baseline, Month 6
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.
Measured: Baseline, Month 6
Change From Baseline in ETCO2 at Month 6
ETCO2 is the amount of CO2 in exhaled air, which assesses ventilation.
Measured: Baseline, Month 6
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
Measured: Baseline, Month 6
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.
Measured: Baseline, Month 6
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.
Measured: Baseline, Month 6
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.
Measured: Baseline, Month 6
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.
Measured: Baseline, Month 6
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.
Measured: Baseline, Month 6
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.
Measured: Month 6
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.
Measured: Baseline up to Month 6
Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.
Measured: Baseline up to Month 3
Level of Disease-Related Biomarker (Glutathione) in Urine
Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.
Measured: Baseline up to Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2015 (estimated)
- Study start14 Jan 2016
- Primary completion23 Feb 2018
- Study completion23 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Matthew B Klein, MD, FACS, Study director, PTC Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02460679
- Sponsor's protocol ID
- EPI589-15-001
- Acronym
- EPI-589
- Status last verified
- Sep 2020
- First submitted
- 21 May 2015
- Last updated
- 14 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2A Safety and Biomarker Study of EPI-589 in Subjects With Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT02460679
- Acronym / sponsor ID
- EPI-589 / EPI589-15-001
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 14 Jan 2016 (actual)
- Primary completion
- 23 Feb 2018 (actual)
- Study completion
- 23 Feb 2018 (actual)
- First posted
- 2 Jun 2015 (estimated)
- Results
- Posted 23 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EPI-589 | Experimental | Drug: EPI-589Participants 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. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- Allergy to EPI-589
- Use of ventilation
- Participation in other intervention studies
- Diagnosis of any other neurologic disease
- Malignancy within the past 2 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EPI-589Also: (R)-troloxamide quinoneAn immediate release film-coated table at a 250 mg dosage strength will be administered per dose and schedule specified in arm. | Drug | EPI-589 |
Primary outcome
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'.
19 secondary outcomes
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
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
Change From Baseline in ALSFRS-R Total Score at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Vital Capacity at Month 6
Time frame: Baseline, Month 6
Change From Baseline in MIP at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Respiratory Rate at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Heart Rate at Month 6
Time frame: Baseline, Month 6
Change From Baseline in SpO2 at Month 6
Time frame: Baseline, Month 6
Change From Baseline in ETCO2 at Month 6
Time frame: Baseline, Month 6
Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6
Time frame: Baseline, Month 6
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
Change From Baseline in Number of Words Participant Read at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Time Spent in Reading at Month 6
Time frame: Baseline, Month 6
Change From Baseline in Number of Words Per Minute Read at Month 6
Time frame: Baseline, Month 6
Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility
Time frame: Month 6
Level of Disease-Related Biomarker (Glutathione) in Plasma
Time frame: Baseline up to Month 6
Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
Time frame: Baseline up to Month 3
Level of Disease-Related Biomarker (Glutathione) in Urine
Time frame: Baseline up to Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew B Klein, MD, FACS study director
PTC Therapeutics
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EPI-589 in people with Amyotrophic Lateral Sclerosis, run by PTC Therapeutics at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Drug-Related Serious Adverse Events (SAEs) (time frame: Baseline (Day 0) to Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2020.