Amyotrophic Lateral Sclerosis
Conditions
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.
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.
Sponsors
PTC Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug-Related Serious Adverse Events (SAEs) | 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | 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 | 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). |
| Change From Baseline in Vital Capacity at Month 6 | Baseline, 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 | 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. |
| Change From Baseline in Respiratory Rate at Month 6 | Baseline, Month 6 | Respiratory rate is the rate at which breathing occurs. |
| Change From Baseline in Heart Rate at Month 6 | Baseline, Month 6 | The heart rate measures the number of times the heart beats per minute. |
| Change From Baseline in SpO2 at Month 6 | 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. |
| Change From Baseline in ETCO2 at Month 6 | Baseline, 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 | Baseline, Month 6 | The failure to thrive as measured by body weight was defined as weight loss of more than 5% from baseline |
| Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) | 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 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) | Baseline, Month 6 | The strength of designated muscle groups was measured using handheld dynamometry. |
| Change From Baseline in Number of Words Participant Read at Month 6 | 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. |
| Change From Baseline in Time Spent in Reading at Month 6 | 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. |
| Change From Baseline in Number of Words Per Minute Read at Month 6 | 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. |
| Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility | 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. |
| Level of Disease-Related Biomarker (Glutathione) in Plasma | 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. |
| Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF) | Baseline up to Month 3 | Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF. |
| Level of Disease-Related Biomarker (Glutathione) in Urine | Baseline up to Month 6 | Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine. |
| Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6 | Baseline, Month 6 | Participants were observed and timed swallowing water as well as solid foods in accordance with a standardized protocol. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EPI-589 Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Investigator Decision | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | EPI-589 |
|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 8.25 |
| Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score | 37.4 units on a scale STANDARD_DEVIATION 6.19 |
| Average Solid Swallowing Time | 12.46 seconds STANDARD_DEVIATION 5.465 |
| Average Water Swallowing Time | 4.68 seconds STANDARD_DEVIATION 3.698 |
| End-Tidal Carbon Dioxide (ETCO2) After 10 minutes supine | 31.186 percentage of CO2 STANDARD_DEVIATION 14.5895 |
| End-Tidal Carbon Dioxide (ETCO2) After 5 minutes supine | 30.964 percentage of CO2 STANDARD_DEVIATION 15.9007 |
| End-Tidal Carbon Dioxide (ETCO2) Sitting | 24.833 percentage of CO2 STANDARD_DEVIATION 16.8444 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Heart Rate After 10 minutes supine | 65.3 beats/minute STANDARD_DEVIATION 12.3 |
| Heart Rate After 5 minutes supine | 63.8 beats/minute STANDARD_DEVIATION 13.46 |
| Heart Rate Sitting | 68.9 beats/minute STANDARD_DEVIATION 10.99 |
| Maximum Inspiratory Pressure (MIP) | 68.2 centimetres of water at (cm H2O) STANDARD_DEVIATION 34.53 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Ankle Dorsi Flexion - Left | 16.47 kilograms STANDARD_DEVIATION 12.188 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Ankle Dorsi Flexion - Right | 13.04 kilograms STANDARD_DEVIATION 10.898 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Elbow Extension - Left | 17.51 kilograms STANDARD_DEVIATION 10.514 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Elbow Extension - Right | 15.36 kilograms STANDARD_DEVIATION 10.482 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Elbow Flexion - Left | 17.16 kilograms STANDARD_DEVIATION 9.074 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Elbow Flexion - Right | 16.52 kilograms STANDARD_DEVIATION 10.508 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Grip - Left | 26.41 kilograms STANDARD_DEVIATION 20.63 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Grip - Right | 26.86 kilograms STANDARD_DEVIATION 18.667 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Hip Flexion - Left | 20.13 kilograms STANDARD_DEVIATION 16.229 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Hip Flexion - Right | 20.82 kilograms STANDARD_DEVIATION 12.738 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Knee Extension - Left | 22.11 kilograms STANDARD_DEVIATION 12.796 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Knee Extension - Right | 22.13 kilograms STANDARD_DEVIATION 13.224 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Knee Flexion - Left | 17.32 kilograms STANDARD_DEVIATION 11.832 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Knee Flexion - Right | 18.02 kilograms STANDARD_DEVIATION 12.987 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Shoulder Flexion - Left | 13.94 kilograms STANDARD_DEVIATION 8.218 |
| Muscle Function, as Assessed by Handheld Dynamometry Parameters Shoulder Flexion - Right | 14.42 kilograms STANDARD_DEVIATION 9.85 |
| Number of Words Participant Read | 100.3 Words STANDARD_DEVIATION 0.45 |
| Number of Words Per Minute Read | 143.529 words/minute STANDARD_DEVIATION 45.4527 |
| Oxygen Saturation (SpO2) After 10 minutes supine | 95.1 percentage of hemoglobin STANDARD_DEVIATION 2.7 |
| Oxygen Saturation (SpO2) After 5 minutes supine | 95.4 percentage of hemoglobin STANDARD_DEVIATION 2.79 |
| Oxygen Saturation (SpO2) Sitting | 96.9 percentage of hemoglobin STANDARD_DEVIATION 1.65 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Respiratory Rate After 10 minutes supine | 14.7 breaths/minute STANDARD_DEVIATION 3.28 |
| Respiratory Rate After 5 minutes supine | 14.7 breaths/minute STANDARD_DEVIATION 3.71 |
| Respiratory Rate Sitting | 15.1 breaths/minute STANDARD_DEVIATION 3.32 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 14 Participants |
| Time Spent in Reading | 48.5 seconds STANDARD_DEVIATION 23.51 |
| Vital Capacity | 97.7 percentage of capacity STANDARD_DEVIATION 18.14 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 15 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
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
Population: Safety population included any participant who received at least 1 dose of EPI-589.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EPI-589 | Number of Participants With Drug-Related Serious Adverse Events (SAEs) | 0 Participants |
Secondary
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
Population: EITT population or safety population included any participant who received at least 1 dose of EPI-589. Here, 'Number analyzed' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPI-589 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) | Month 1 | 7762.7 hours*nanograms/milliliter | Standard Error 721.1 |
| EPI-589 | Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) | Month 3 | 6878.8 hours*nanograms/milliliter | Standard Error 401.1 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPI-589 | Change From Baseline in ALSFRS-R Total Score at Month 6 | -4.1 units on a scale | Standard Deviation 4.03 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPI-589 | Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6 | Average Solid Swallowing Time | 4.80 seconds | Standard Deviation 11.718 |
| EPI-589 | Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6 | Average Water Swallowing Time | 6.65 seconds | Standard Deviation 20.95 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPI-589 | Change From Baseline in ETCO2 at Month 6 | Sitting | 2.384 percentage of CO2 | Standard Deviation 8.2343 |
| EPI-589 | Change From Baseline in ETCO2 at Month 6 | After 5 minutes supine | 0.605 percentage of CO2 | Standard Deviation 5.0262 |
| EPI-589 | Change From Baseline in ETCO2 at Month 6 | After 10 minutes supine | 7.112 percentage of CO2 | Standard Deviation 9.6591 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPI-589 | Change From Baseline in Heart Rate at Month 6 | Sitting | 5.2 beats/minute | Standard Deviation 10.74 |
| EPI-589 | Change From Baseline in Heart Rate at Month 6 | After 5 minutes supine | 7.1 beats/minute | Standard Deviation 7.49 |
| EPI-589 | Change From Baseline in Heart Rate at Month 6 | After 10 minutes supine | 7.2 beats/minute | Standard Deviation 8.39 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPI-589 | Change From Baseline in MIP at Month 6 | 2.4 cm H2O | Standard Deviation 24.83 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPI-589 | 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) | Grip - Left | -9.69 kilograms | Standard Deviation 15.33 |
| EPI-589 | 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) | Grip - Right | -7.28 kilograms | Standard Deviation 7.207 |
| EPI-589 | 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) | Shoulder Flexion - Left | -4.53 kilograms | Standard Deviation 6.922 |
| EPI-589 | 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) | Shoulder Flexion - Right | -5.43 kilograms | Standard Deviation 8.915 |
| EPI-589 | 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) | Knee Extension - Left | -5.42 kilograms | Standard Deviation 10.254 |
| EPI-589 | 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) | Knee Extension - Right | -5.05 kilograms | Standard Deviation 11.505 |
| EPI-589 | 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) | Knee Flexion - Left | -4.63 kilograms | Standard Deviation 8.237 |
| EPI-589 | 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) | Knee Flexion - Right | -4.01 kilograms | Standard Deviation 9.17 |
| EPI-589 | 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) | Hip Flexion - Left | -6.84 kilograms | Standard Deviation 12.579 |
| EPI-589 | 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) | Hip Flexion - Right | -5.60 kilograms | Standard Deviation 9.627 |
| EPI-589 | 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) | Elbow Flexion - Left | -4.84 kilograms | Standard Deviation 8.377 |
| EPI-589 | 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) | Elbow Flexion - Right | -3.28 kilograms | Standard Deviation 8.186 |
| EPI-589 | 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) | Elbow Extension - Left | -5.77 kilograms | Standard Deviation 10.511 |
| EPI-589 | 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) | Elbow Extension - Right | -4.28 kilograms | Standard Deviation 9.048 |
| EPI-589 | 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) | Ankle Dorsi Flexion - Left | -6.12 kilograms | Standard Deviation 7.609 |
| EPI-589 | 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) | Ankle Dorsi Flexion - Right | -4.89 kilograms | Standard Deviation 7.529 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPI-589 | Change From Baseline in Number of Words Participant Read at Month 6 | 0.0 words | Standard Deviation 0 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPI-589 | Change From Baseline in Number of Words Per Minute Read at Month 6 | -147.535 words/minute | Standard Deviation 26.7792 |
Secondary
Change From Baseline in Respiratory Rate at Month 6
Respiratory rate is the rate at which breathing occurs.
Time frame: Baseline, Month 6
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPI-589 | Change From Baseline in Respiratory Rate at Month 6 | Sitting | 0.3 breaths/minute | Standard Deviation 3.45 |
| EPI-589 | Change From Baseline in Respiratory Rate at Month 6 | After 5 minutes supine | -0.6 breaths/minute | Standard Deviation 5.57 |
| EPI-589 | Change From Baseline in Respiratory Rate at Month 6 | After 10 minutes supine | 0.0 breaths/minute | Standard Deviation 4.32 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPI-589 | Change From Baseline in SpO2 at Month 6 | Sitting | -1.0 percentage of hemoglobin | Standard Deviation 1.71 |
| EPI-589 | Change From Baseline in SpO2 at Month 6 | After 5 minutes supine | -0.8 percentage of hemoglobin | Standard Deviation 4.64 |
| EPI-589 | Change From Baseline in SpO2 at Month 6 | After 10 minutes supine | -0.1 percentage of hemoglobin | Standard Deviation 3.55 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPI-589 | Change From Baseline in Time Spent in Reading at Month 6 | 5.5 seconds | Standard Deviation 11.78 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPI-589 | Change From Baseline in Vital Capacity at Month 6 | -3.1 percentage of capacity | Standard Deviation 9.36 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EPI-589 | Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 6 | 2 Participants |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants with both baseline and Month 3 glutathione in CSF data.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| EPI-589 | Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF) | Baseline | 0.13 µM |
| EPI-589 | Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF) | Month 3 | 0.13 µM |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants with both baseline and Month 6 glutathione in plasma data.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| EPI-589 | Level of Disease-Related Biomarker (Glutathione) in Plasma | Baseline | 1.34 µM |
| EPI-589 | Level of Disease-Related Biomarker (Glutathione) in Plasma | Month 6 | 2.73 µM |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants with both baseline and Month 6 glutathione in urine data.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| EPI-589 | Level of Disease-Related Biomarker (Glutathione) in Urine | Baseline | 0.12 µM |
| EPI-589 | Level of Disease-Related Biomarker (Glutathione) in Urine | Month 6 | 0.17 µM |
Secondary
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
Population: EITT population or safety population included any participant who received at least 1 dose of EPI-589. Here, 'Number analyzed' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPI-589 | Maximum Observed Plasma Concentration (Cmax) | Month 1 | 5179.0 ng/mL | Standard Error 930.3 |
| EPI-589 | Maximum Observed Plasma Concentration (Cmax) | Month 3 | 4167.8 ng/mL | Standard Error 642.2 |
Secondary
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
Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EPI-589 | Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility | Normal Loudness | 10 Participants |
| EPI-589 | Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility | Normal Nasality | 6 Participants |
| EPI-589 | Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility | Normal Intelligibility | 6 Participants |