Distal Myopathy, Nonaka Type, Distal Myopathy With Rimmed Vacuoles, GNE Myopathy, Hereditary Inclusion Body Myopathy, Inclusion Body Myopathy 2, Quadriceps Sparing Myopathy
Conditions
Keywords
GNE Myopathy, Nonaka, GNEM, Hereditary Inclusion Body Myopathy, HIBM, DMRV, QSM
Brief summary
The primary objective of this Phase 2 study is to evaluate the safety of open-label 6 g/day Ace-ER in GNEM participants with severe ambulatory impairment.
Interventions
DRUGAceneuramic Acid Extended-Release
oral tablets
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, aged ≥ 18 years old * Willing and able to provide written, signed informed consent after the nature of the study has been explained, and before any research-related procedures are conducted * Have a documented diagnosis of GNEM, HIBM, distal myopathy with rimmed vacuoles (DMRV), or Nonaka disease due to previously demonstrated mutations in the gene encoding the GNE/N-acetylmannosamine kinase (MNK) enzyme (genotyping will not be conducted in this study). * Should meet the criteria for severe ambulatory impairment defined below: * Unable to rise from a seated position to standing without help from another person, assistive device(s), stationary object, or other support AND * Unable to walk without the assistance of another person OR if able to walk (use of assistive device(s) permitted), requires at least 2 minutes to walk 40 meters (one full lap of the 6-minute walk test \[6MWT\] course) AND * Use of wheelchair or scooter for activities outside of the home or unable to leave the home independently * Willing and able to comply with all study procedures * Participants of child-bearing potential or with partners of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use highly effective method of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation or true abstinence (when this is in line with the preferred and usual lifestyle of the subject) which means not having sex because the subject chooses not to), from the period following the signing of the informed consent through 30 days after last dose of study drug * Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause for at least two years, have had tubal ligation at least one year prior to Screening, or who have had a total hysterectomy or bilateral salpingo-oophorectomy
Exclusion criteria
* Ingestion of N-acetyl-D-mannosamine (ManNAc), SA, or related metabolites; intravenous immunoglobulin (IVIG); or anything that can be metabolized to produce SA in the body within 60 days prior to the Screening Visit * Prior participation in a clinical trial involving treatment with Ace-ER/placebo and/or Sialic Acid immediate release (SA-IR) in the past year * Has had any hypersensitivity to aceneuramic acid or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects * Has serum transaminase (i.e. aspartate aminotransferase \[AST\] or gamma-glutamyl transpeptidase \[GGT\]) levels greater than 3X the upper limit of normal (ULN) for age/gender, or serum creatinine of greater than 2X ULN at Screening * Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study * Use of any investigational product or investigational medical device within 30 days prior to Screening, or anticipated requirement for any investigational agent prior to completion of all scheduled study assessments * Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment or may not allow safe participation in the study * Has a concurrent disease, active suicidal ideation, or other condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or would affect safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation | 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study) | An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction that at any dose, in the view of either the Investigator or Ultragenyx, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect. TEAEs were defined as any AE that occurred after the first dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations | 48 weeks | Complete physical examinations included assessments of general appearance; head, eyes, ears, nose, and throat; the cardiovascular, dermatologic, lymphatic, respiratory, GI, musculoskeletal, and neurologic systems. The neurologic system examination included assessments of cognition, cranial nerves, motor function, coordination and gait, reflexes, and sensory function. Brief physical examinations included assessments of general appearance, cardiovascular and respiratory systems, and a focus on any presenting complaints. |
| Number of Participants With Clinically Significant Changes From Baseline In Vital Signs | 48 weeks | Vital signs included seated systolic blood pressure and diastolic blood pressure, heart rate, respiration rate, and temperature. |
| Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results | 48 weeks | The clinical laboratory evaluations performed included serum chemistry, complete blood count (hematology), and urinalysis. |
| Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline | 48 weeks | As evaluated by the Columbia Suicide Severity Rating Scale (C-SSRS), a participant-rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses). |
| Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time | Baseline, Weeks 12, 24, 36, and 48 | GNEM-FAS Expanded Version Mobility subscale scores have 13 items and range from 0 to 52 with higher scores representing greater mobility. Analyzed using a repeated measure generalized estimation equation (GEE) model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure. |
| Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time | Baseline, Weeks 12, 24, 36, and 48 | GNEM-FAS Expanded Version Upper Extremity subscale scores have 9 items and range from 0 to 36 with higher scores representing more skilled, independent use of the arms during functional activity performance. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure. |
| Number of Participants Taking Prior and Concomitant Medications | 48 weeks | Prior medications are any medications which started before the date of the first dose of investigational product. Concomitant medications are any medications that are taken on or after the date of the first dose of investigational product excluding concomitant medications started after the date of the last dose of investigational product. |
| Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time | Baseline, Weeks 12, 24, 36, and 48 | GNEM-FAS Expanded Version Total Score were calculated as the sum of the subscale Scores range from 0 to 120 with higher scores representing greater independence with functional activities. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure. |
| Change From Baseline in HHD Raw Strength (Grip) Over Time | Baseline, Weeks 12, 24, 36, and 48 | Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure. |
| Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time | Baseline, Weeks 12, 24, 36, and 48 | Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure. |
| Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time | Baseline, Weeks 12, 24, 36, and 48 | Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure. |
| Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time | Baseline, Weeks 12, 24, 36, and 48 | Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure. |
| Change From Baseline in HHD Raw Strength (Key Pinch) Over Time | Baseline, Weeks 12, 24, 36, and 48 | Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. |
| Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time | Baseline, Weeks 12, 24, 36, and 48 | GNEM-FAS Expanded Version Self-Care subscale scores have 8 items range from 0 to 32 with higher scores representing greater independence with functional care activities. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure. |
Countries
Bulgaria, Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UX001 6g/Day Open-label UX001 6000 mg (6 g) total daily dose administered orally divided into a 3-times-daily regimen. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Discontinuation of Study by Sponsor | 26 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | UX001 6g/Day |
|---|---|
| Age, Continuous | 46.0 years STANDARD_DEVIATION 13.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy Functional Activities Scale(GNEM-FAS) Mobility Score | 10.63 units on a scale STANDARD_DEVIATION 7.816 |
| GNEM-FAS Self-Care Domain Score | 13.00 units on a scale STANDARD_DEVIATION 7.413 |
| GNEM-FAS Total Score | 38.83 units on a scale STANDARD_DEVIATION 23.116 |
| GNEM-FAS Upper Extremity Domain Score | 15.20 units on a scale STANDARD_DEVIATION 8.897 |
| Hand-Held Dynamometry (HHD) Raw Strength: Average Grip | 5.535 kgf STANDARD_DEVIATION 7.6778 |
| HHD Lower Extremity Muscle Strength: Average Knee Extension | 10.50 kgf STANDARD_DEVIATION 8.001 |
| HHD Raw Strength: Average Shoulder Abduction | 3.880 kgf STANDARD_DEVIATION 4.4583 |
| HHD Raw Strength: Average Wrist Extension | 3.532 kgf STANDARD_DEVIATION 3.5177 |
| HHD Raw Strength: Key Pinch | 1.790 kgf STANDARD_DEVIATION 2.1614 |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Other (Not Specified) | 9 Participants |
| Race/Ethnicity, Customized White | 31 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 42 |
| other Total, other adverse events | 26 / 42 |
| serious Total, serious adverse events | 1 / 42 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction that at any dose, in the view of either the Investigator or Ultragenyx, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect. TEAEs were defined as any AE that occurred after the first dose of study drug.
Time frame: 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)
Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UX001 6g/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation | TEAEs | 30 Participants |
| UX001 6g/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation | Serious TEAEs | 1 Participants |
| UX001 6g/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation | TEAEs Causing Study Drug Discontinuation | 1 Participants |
| UX001 6g/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation | TEAEs Causing Study Discontinuation | 1 Participants |
Secondary
Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time
GNEM-FAS Expanded Version Mobility subscale scores have 13 items and range from 0 to 52 with higher scores representing greater mobility. Analyzed using a repeated measure generalized estimation equation (GEE) model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time | Week 12 | 0.16 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time | Week 24 | -0.65 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time | Week 36 | -0.69 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time | Week 48 | -1.03 units on a scale |
Comparison: Week 12p-value: 0.5303GEE model
Comparison: Week 24p-value: 0.1646GEE model
Comparison: Week 36p-value: 0.1189GEE model
Comparison: Week 48p-value: 0.0706GEE model
Secondary
Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time
GNEM-FAS Expanded Version Self-Care subscale scores have 8 items range from 0 to 32 with higher scores representing greater independence with functional care activities. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time | Week 12 | -0.39 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time | Week 24 | -0.71 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time | Week 36 | -0.83 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time | Week 48 | -0.40 units on a scale |
Comparison: Week 12p-value: 0.0568GEE model
Comparison: Week 24p-value: 0.0533GEE model
Comparison: Week 36p-value: 0.0459GEE model
Comparison: Week 48p-value: 0.5678GEE model
Secondary
Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time
GNEM-FAS Expanded Version Total Score were calculated as the sum of the subscale Scores range from 0 to 120 with higher scores representing greater independence with functional activities. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time | Week 12 | 0.35 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time | Week 24 | -1.95 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time | Week 36 | -2.02 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time | Week 48 | -3.34 units on a scale |
Comparison: Week 12p-value: 0.581GEE model
Comparison: Week 24p-value: 0.0465GEE model
Comparison: Week 36p-value: 0.1047GEE model
Comparison: Week 48p-value: 0.0661GEE model
Secondary
Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time
GNEM-FAS Expanded Version Upper Extremity subscale scores have 9 items and range from 0 to 36 with higher scores representing more skilled, independent use of the arms during functional activity performance. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time | Week 12 | 0.57 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time | Week 24 | -0.62 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time | Week 36 | -0.51 units on a scale |
| UX001 6g/Day | Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time | Week 48 | -1.91 units on a scale |
Comparison: Week 12p-value: 0.0715GEE model
Comparison: Week 24p-value: 0.1697GEE model
Comparison: Week 36p-value: 0.3428GEE model
Comparison: Week 48p-value: 0.0642GEE model
Secondary
Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time
Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| UX001 6g/Day | Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time | Week 12 | 0.80 kgf |
| UX001 6g/Day | Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time | Week 24 | 1.35 kgf |
| UX001 6g/Day | Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time | Week 36 | 2.05 kgf |
| UX001 6g/Day | Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time | Week 48 | 2.45 kgf |
Comparison: Week 12p-value: 0.0872GEE model
Comparison: Week 24p-value: 0.0073GEE model
Comparison: Week 36p-value: 0.0086GEE model
Comparison: Week 48p-value: 0.0489GEE model
Secondary
Change From Baseline in HHD Raw Strength (Grip) Over Time
Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Grip) Over Time | Week 12 | 0.258 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Grip) Over Time | Week 24 | 0.128 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Grip) Over Time | Week 36 | 0.038 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Grip) Over Time | Week 48 | -0.261 kgf |
Comparison: Week 12p-value: 0.1615GEE model
Comparison: Week 24p-value: 0.6201GEE model
Comparison: Week 36p-value: 0.9229GEE model
Comparison: Week 48p-value: 0.6307GEE model
Secondary
Change From Baseline in HHD Raw Strength (Key Pinch) Over Time
Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Key Pinch) Over Time | Week 24 | 0.112 kgf | Standard Deviation 0.6534 |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Key Pinch) Over Time | Week 12 | 0.110 kgf | Standard Deviation 0.7083 |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Key Pinch) Over Time | Week 36 | 0.049 kgf | Standard Deviation 0.809 |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Key Pinch) Over Time | Week 48 | 0.318 kgf | Standard Deviation 0.9509 |
Secondary
Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time
Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time | Week 12 | 0.339 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time | Week 24 | 0.379 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time | Week 36 | 0.437 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time | Week 48 | -0.277 kgf |
Comparison: Week 12p-value: 0.0088GEE model
Comparison: Week 24p-value: 0.2213GEE model
Comparison: Week 36p-value: 0.018GEE model
Comparison: Week 48p-value: 0.197GEE model
Secondary
Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time
Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Analyzed using a repeated measure GEE model, which includes the change from baseline as the dependent variable, visit as a fixed factor, and the baseline value as a covariate. Compound symmetry is used as the covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set: all participants with a baseline measurement and at least 1 postbaseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time | Week 12 | 0.235 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time | Week 24 | 0.152 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time | Week 36 | 0.358 kgf |
| UX001 6g/Day | Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time | Week 48 | -0.123 kgf |
Comparison: Week 12p-value: 0.0752GEE model
Comparison: Week 24p-value: 0.6403GEE model
Comparison: Week 36p-value: 0.2316GEE model
Comparison: Week 48p-value: 0.7635GEE model
Secondary
Number of Participants Taking Prior and Concomitant Medications
Prior medications are any medications which started before the date of the first dose of investigational product. Concomitant medications are any medications that are taken on or after the date of the first dose of investigational product excluding concomitant medications started after the date of the last dose of investigational product.
Time frame: 48 weeks
Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UX001 6g/Day | Number of Participants Taking Prior and Concomitant Medications | Prior Medications | 31 Participants |
| UX001 6g/Day | Number of Participants Taking Prior and Concomitant Medications | Concomitant Medications | 33 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results
The clinical laboratory evaluations performed included serum chemistry, complete blood count (hematology), and urinalysis.
Time frame: 48 weeks
Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| UX001 6g/Day | Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results | Hematology | 0 participants |
| UX001 6g/Day | Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results | Clinical Chemistry | 2 participants |
| UX001 6g/Day | Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results | Urinalysis | 0 participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations
Complete physical examinations included assessments of general appearance; head, eyes, ears, nose, and throat; the cardiovascular, dermatologic, lymphatic, respiratory, GI, musculoskeletal, and neurologic systems. The neurologic system examination included assessments of cognition, cranial nerves, motor function, coordination and gait, reflexes, and sensory function. Brief physical examinations included assessments of general appearance, cardiovascular and respiratory systems, and a focus on any presenting complaints.
Time frame: 48 weeks
Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UX001 6g/Day | Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations | 0 participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline In Vital Signs
Vital signs included seated systolic blood pressure and diastolic blood pressure, heart rate, respiration rate, and temperature.
Time frame: 48 weeks
Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UX001 6g/Day | Number of Participants With Clinically Significant Changes From Baseline In Vital Signs | 0 participants |
Secondary
Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline
As evaluated by the Columbia Suicide Severity Rating Scale (C-SSRS), a participant-rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses).
Time frame: 48 weeks
Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UX001 6g/Day | Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline | Overall Suicidal Ideation: Baseline | 7 Participants |
| UX001 6g/Day | Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline | Overall Suicidal Behaviors: Baseline | 1 Participants |
| UX001 6g/Day | Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline | Overall Suicidal Behaviors: Post-Baseline | 0 Participants |
| UX001 6g/Day | Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline | Non-Suicide Self-Injurious Behavior: Baseline | 0 Participants |
| UX001 6g/Day | Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline | Non-Suicide Self-Injurious Behavior: Post-Baseline | 0 Participants |
| UX001 6g/Day | Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline | Completed Suicide: Post-Baseline | 0 Participants |
| UX001 6g/Day | Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline | Overall Suicidal Ideation: Post-Baseline | 1 Participants |