Carnitine-acylcarnitine Translocase (CACT) Deficiency, Carnitine Palmitoyltransferase (CPT I or CPT II) Deficiency, Long-chain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency, Trifunctional Protein (TFP) Deficiency, Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency
Conditions
Keywords
Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD), carnitine palmitoyltransferase (CPT I or CPT II) deficiency, very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency, trifunctional protein (TFP) deficiency, carnitine-acylcarnitine translocase (CACT) deficiency, Triheptanoin, UX007, C7
Brief summary
The primary objective of this study is to evaluate the long-term safety and efficacy of UX007 in participants with LC-FAOD. The secondary objectives of this study are to evaluate the effect of UX007 on energy metabolism in LC-FAOD and evaluate the impact of UX007 on clinical events associated with LC-FAOD.
Interventions
DRUGUX007
Administered orally (PO) with food or by gastrostomy tube, at the target dose range of 25-35% of total calories.
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, 6 months of age or older 2. Prior participation in a clinical study assessing UX007/triheptanoin treatment for LC FAOD. Study Sponsors/Collaborators include: Oregon Health & Science University, University of Pittsburgh, and Ultragenyx Pharmaceutical (ClinicalTrials.gov Identifiers: NCT01379625, NCT01461304, and NCT01886378). Patients who received UX007/triheptanoin treatment as part of other clinical studies; investigator sponsored trials (IST); expanded access/compassionate use treatment programs; or patients who are treatment naïve (i.e., naïve to both UX007 and food-grade triheptanoin), have failed conventional therapy and, in the opinion of the Investigator and Sponsor, have documented clear unmet need, may also be eligible at the discretion of the Sponsor 3. Confirmed diagnosis of LC-FAOD including: CPT I or CPT II deficiency, VLCAD deficiency, LCHAD deficiency, TFP deficiency, or CACT deficiency. Information on diagnosis will be obtained from medical records and should include confirmed diagnosis by results of acylcarnitine profiles, fatty acid oxidation probe studies in cultured fibroblasts, and/or mutation analysis 4. Willing and able to complete all aspects of the study through the end of the study, including visits and tests, documentation of symptoms and diet, and administration of study medications. If a minor, have a caregiver(s) willing and able to assist in all applicable study requirements 5. Provide written informed consent (subjects aged ≥ 18 years), or provide written assent (where appropriate) and have a legally authorized representative willing and able to provide written informed consent, after the nature of the study has been explained and prior to any research-related procedures. 6. Females of child-bearing potential must have a negative urine pregnancy test at Baseline and be willing to have additional pregnancy tests during the study. Females considered not of child-bearing potential include those who have not experienced menarche, are post-menopausal (defined as having no menses for at least 12 months without an alternative medical cause), or are permanently sterile due to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy 7. Participants of child-bearing potential or fertile males with partners of child-bearing potential who are sexually active must consent to use a highly effective method of contraception as determined by the Investigator from the period following the signing of the informed consent through 30 days after last dose of study drug
Exclusion criteria
1. Diagnosis of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency, short- or medium-chain FAOD, ketone body metabolism defect, propionic acidemia or methylmalonic acidemia 2. Patient qualifies for any other clinical trial designed to progressively evaluate the safety and efficacy of triheptanoin in LC-FAOD 3. Any known hypersensitivity to triheptanoin that, in the judgment of the Investigator, places the subject at increased risk for adverse effects 4. Pregnant and/or breastfeeding an infant at Screening or planning to become pregnant (self or partner) at any time during the study 5. Have any co-morbid conditions, including unstable major organ-system disease(s) that in the opinion of the Investigator, places the subject at increased risk of complications, interferes with study participation or compliance, or confounds study objectives, or unwilling to discontinue prohibited medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized LC-FAOD Major Clinical Events (MCEs) Rate: 18 Months Pre- and Entire UX007 Period Comparison for UX007-CL201-Rollover Cohort | Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days) | The annualized LC-FAOD MCE rate, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, defined as any visit to the emergency room (ER)/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25 |
| Annualized LC-FAOD MCEs Rate: 18 Months Pre- and Entire UX007 Period Comparison for IST/Other Cohort and Triheptanoin-Naïve Cohort | Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days) | The annualized LC-FAOD MCE rate, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, defined as any visit to the emergency room (ER)/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25 |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Post-UX007 treatment through the end of treatment (up to 2072 days) plus 30-35 days | An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. A serious adverse event (SAE) 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; a congenital anomaly/birth defect; an important medical event. AEs were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (mild=1, moderate=2, severe=3, life-threatening=4, death=5). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Baseline, Month 12, Month 18, Month 24, Month 30, Month 36, Month 48, Month 60 | — |
| Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Baseline, Month 12, Month 24, Month 36 | The Z-scores express the deviation (or how far away) the measure is from the mean LVEF based on the size or age of the pediatric participants: Z-score=0 indicates the participant is exactly the same as the mean of the healthy general population. Z-score=-1 indicates it's 1 standard deviation below the mean of the healthy population. Z-score=+1 indicates it's 1 standard deviation above the mean. |
| Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Baseline, Month 12, Month 24, Month 30, Month 36, Month 48, Month 60 | Fractional shortening is calculated by measuring the percentage change in left ventricular diameter during systole. A negative value indicates less ventricular/muscular contractility, and a positive value indicates more ventricular/muscular contractility. |
| Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Baseline, Month 12, Month 24, Month 36, Month 48, Month 60 | The Z-scores express the deviation (or how far away) the measure is from the mean LVSF based on the size or age of the pediatric participants: Z-score=0 indicates the participant is exactly the same as the mean of the healthy general population. Z-score=-1 indicates it's 1 standard deviation below the mean of the healthy population. Z-score=+1 indicates it's 1 standard deviation above the mean. |
| Annualized Duration Rate of All MCEs | Post-UX007 treatment through the end of the study (up to 2072 days) | The annualized duration rate of LC-FAOD MCEs, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, and defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25. |
| Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Baseline, Month 12, Month 24, Month 36, Month 48, Month 60 | — |
| Annualized Duration Rate of Rhabdomyolysis MCEs | Post-UX007 treatment through the end of the study (up to 2072 days) | The annualized duration rate of LC-FAOD skeletal myopathy (rhabdomyolysis) MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25. |
| Annualized Event Rate of Cardiomyopathy MCEs | Post-UX007 treatment through the end of the study (up to 2072 days) | The annualized event rate of LC-FAOD major events inclusive of cardiomyopathy events, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25. |
| Annualized Duration Rate of Cardiomyopathy MCEs | Post-UX007 treatment through the end of the study (up to 2072 days) | The annualized duration rate of LC-FAOD cardiomyopathy MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25 |
| Annualized Event Rate of Hypoglycemic MCEs | Post-UX007 treatment through the end of the study (up to 2072 days) | The annualized event rate of LC-FAOD major events of hepatic (hypoglycemia) events, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25. |
| Annualized Duration Rate of Hypoglycemic MCEs | Post-UX007 treatment through the end of the study (up to 2072 days) | The annualized duration rate of LC-FAOD hepatic (hypoglycemia) MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25. |
| Annualized Event Rate of Rhabdomyolysis MCEs | Post-UX007 treatment through the end of the study (up to 2072 days) | The annualized event rate of LC-FAOD major events of skeletal myopathy (rhabdomyolysis), defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25. |
| Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Baseline, Month 12, Month 24, Month 36, Month 48, Month 60 | — |
| Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Baseline, Month 12, Month 24, Month 36, Month 48, Month 60 | — |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UX007-CL201-Rollover Cohort Participants who participated in the UX007-CL201 study (NCT01886378) receive UX007, administered orally with food or by gastronomy tube (usually 4 times per day: breakfast, lunch, dinner, and before bed), at the target dose range of 25-35% of total calories. | 24 |
| IST/Other Cohort Participants who were previously treated with UX007/triheptanoin (including food-grade triheptanoin) in an investigator sponsored trial (IST) or another UX007/triheptanoin study receive UX007, administered orally with food or by gastronomy tube (usually 4 times per day: breakfast, lunch, dinner, and before bed), at the target dose range of 25-35% of total calories. | 37 |
| Triheptanoin-Naïve Cohort Participants who are UX007 treatment-naïve (i.e., naïve to both UX007 and food-grade triheptanoin), or who had failed conventional therapy (including those who participated in UX007-CL201 study previously but were off UX007 for more than 2 years preceding enrollment into CL202) receive UX007, administered orally with food or by gastronomy tube (usually 4 times per day: breakfast, lunch, dinner, and before bed), at the target dose range of 25-35% of total calories. | 33 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
| Overall Study | Death | 2 | 2 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 2 | 0 |
| Overall Study | Subject Non-Compliance | 0 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 6 |
Baseline characteristics
| Characteristic | UX007-CL201-Rollover Cohort | IST/Other Cohort | Triheptanoin-Naïve Cohort | Total |
|---|---|---|---|---|
| Age, Continuous | 13.16 years STANDARD_DEVIATION 14.31 | 17.69 years STANDARD_DEVIATION 14.49 | 9.33 years STANDARD_DEVIATION 9.745 | 13.60 years STANDARD_DEVIATION 13.333 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 5 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 30 Participants | 28 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 21 Participants | 33 Participants | 28 Participants | 82 Participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 14 Participants | 45 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 19 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 24 | 2 / 37 | 1 / 33 | 5 / 94 |
| other Total, other adverse events | 24 / 24 | 34 / 37 | 32 / 33 | 90 / 94 |
| serious Total, serious adverse events | 20 / 24 | 28 / 37 | 22 / 33 | 70 / 94 |
Outcome results
Primary
Annualized LC-FAOD Major Clinical Events (MCEs) Rate: 18 Months Pre- and Entire UX007 Period Comparison for UX007-CL201-Rollover Cohort
The annualized LC-FAOD MCE rate, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, defined as any visit to the emergency room (ER)/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25
Time frame: Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized LC-FAOD Major Clinical Events (MCEs) Rate: 18 Months Pre- and Entire UX007 Period Comparison for UX007-CL201-Rollover Cohort | Pre-UX007 Period | 1.76 events/year | Standard Deviation 1.64 |
| UX007-CL201-Rollover Cohort | Annualized LC-FAOD Major Clinical Events (MCEs) Rate: 18 Months Pre- and Entire UX007 Period Comparison for UX007-CL201-Rollover Cohort | UX007 Treatment Period | 1.00 events/year | Standard Deviation 1 |
p-value: 0.0347Paired T-test
Primary
Annualized LC-FAOD MCEs Rate: 18 Months Pre- and Entire UX007 Period Comparison for IST/Other Cohort and Triheptanoin-Naïve Cohort
The annualized LC-FAOD MCE rate, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, defined as any visit to the emergency room (ER)/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25
Time frame: Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment. Per protocol, pre-UX007 MCE data was not collected in the IST/Other Cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized LC-FAOD MCEs Rate: 18 Months Pre- and Entire UX007 Period Comparison for IST/Other Cohort and Triheptanoin-Naïve Cohort | UX007 Treatment Period | 0.57 events/year |
| Triheptanoin-Naïve Cohort | Annualized LC-FAOD MCEs Rate: 18 Months Pre- and Entire UX007 Period Comparison for IST/Other Cohort and Triheptanoin-Naïve Cohort | Pre-UX007 Period | 2.00 events/year |
| Triheptanoin-Naïve Cohort | Annualized LC-FAOD MCEs Rate: 18 Months Pre- and Entire UX007 Period Comparison for IST/Other Cohort and Triheptanoin-Naïve Cohort | UX007 Treatment Period | 0.28 events/year |
p-value: 0.0343Wilcoxon Signed Rank Test
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs
An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. A serious adverse event (SAE) 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; a congenital anomaly/birth defect; an important medical event. AEs were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (mild=1, moderate=2, severe=3, life-threatening=4, death=5).
Time frame: Post-UX007 treatment through the end of treatment (up to 2072 days) plus 30-35 days
Population: Safety Analysis Set: participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | >= 1 TEAE | 24 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related TEAEs | 14 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related Gastrointestinal (GI) TEAEs | 10 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Grade 3 TEAEs | 16 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Grade 4 TEAEs | 3 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Serious TEAEs | 20 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related Serious TEAEs | 1 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Treatment Discontinuation | 1 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Study Discontinuation | 0 participants |
| UX007-CL201-Rollover Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Death | 2 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Study Discontinuation | 1 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | >= 1 TEAE | 35 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Serious TEAEs | 28 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Grade 4 TEAEs | 2 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related TEAEs | 22 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Death | 2 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Treatment Discontinuation | 1 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related Gastrointestinal (GI) TEAEs | 19 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related Serious TEAEs | 1 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Grade 3 TEAEs | 26 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Treatment Discontinuation | 1 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Grade 3 TEAEs | 18 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Grade 4 TEAEs | 2 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Serious TEAEs | 22 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Study Discontinuation | 1 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related Serious TEAEs | 3 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | >= 1 TEAE | 32 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | TEAEs Leading to Death | 1 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related TEAEs | 28 participants |
| Triheptanoin-Naïve Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs | Treatment-Related Gastrointestinal (GI) TEAEs | 27 participants |
Secondary
Annualized Duration Rate of All MCEs
The annualized duration rate of LC-FAOD MCEs, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, and defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25.
Time frame: Post-UX007 treatment through the end of the study (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized Duration Rate of All MCEs | 2.123 days/year |
| Triheptanoin-Naïve Cohort | Annualized Duration Rate of All MCEs | 2.487 days/year |
| Triheptanoin-Naïve Cohort | Annualized Duration Rate of All MCEs | 0.796 days/year |
Secondary
Annualized Duration Rate of Cardiomyopathy MCEs
The annualized duration rate of LC-FAOD cardiomyopathy MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25
Time frame: Post-UX007 treatment through the end of the study (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized Duration Rate of Cardiomyopathy MCEs | 0.000 days/year |
| Triheptanoin-Naïve Cohort | Annualized Duration Rate of Cardiomyopathy MCEs | 0.000 days/year |
| Triheptanoin-Naïve Cohort | Annualized Duration Rate of Cardiomyopathy MCEs | 0.000 days/year |
Secondary
Annualized Duration Rate of Hypoglycemic MCEs
The annualized duration rate of LC-FAOD hepatic (hypoglycemia) MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25.
Time frame: Post-UX007 treatment through the end of the study (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized Duration Rate of Hypoglycemic MCEs | 0.000 days/year |
| Triheptanoin-Naïve Cohort | Annualized Duration Rate of Hypoglycemic MCEs | 0.000 days/year |
| Triheptanoin-Naïve Cohort | Annualized Duration Rate of Hypoglycemic MCEs | 0.000 days/year |
Secondary
Annualized Duration Rate of Rhabdomyolysis MCEs
The annualized duration rate of LC-FAOD skeletal myopathy (rhabdomyolysis) MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25.
Time frame: Post-UX007 treatment through the end of the study (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized Duration Rate of Rhabdomyolysis MCEs | 2.123 days/year |
| Triheptanoin-Naïve Cohort | Annualized Duration Rate of Rhabdomyolysis MCEs | 2.487 days/year |
| Triheptanoin-Naïve Cohort | Annualized Duration Rate of Rhabdomyolysis MCEs | 0.448 days/year |
Secondary
Annualized Event Rate of Cardiomyopathy MCEs
The annualized event rate of LC-FAOD major events inclusive of cardiomyopathy events, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25.
Time frame: Post-UX007 treatment through the end of the study (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized Event Rate of Cardiomyopathy MCEs | 0.000 event/year |
| Triheptanoin-Naïve Cohort | Annualized Event Rate of Cardiomyopathy MCEs | 0.000 event/year |
| Triheptanoin-Naïve Cohort | Annualized Event Rate of Cardiomyopathy MCEs | 0.000 event/year |
Secondary
Annualized Event Rate of Hypoglycemic MCEs
The annualized event rate of LC-FAOD major events of hepatic (hypoglycemia) events, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25.
Time frame: Post-UX007 treatment through the end of the study (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized Event Rate of Hypoglycemic MCEs | 0.000 events/year |
| Triheptanoin-Naïve Cohort | Annualized Event Rate of Hypoglycemic MCEs | 0.000 events/year |
| Triheptanoin-Naïve Cohort | Annualized Event Rate of Hypoglycemic MCEs | 0.000 events/year |
Secondary
Annualized Event Rate of Rhabdomyolysis MCEs
The annualized event rate of LC-FAOD major events of skeletal myopathy (rhabdomyolysis), defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25.
Time frame: Post-UX007 treatment through the end of the study (up to 2072 days)
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007-CL201-Rollover Cohort | Annualized Event Rate of Rhabdomyolysis MCEs | 0.352 events/year |
| Triheptanoin-Naïve Cohort | Annualized Event Rate of Rhabdomyolysis MCEs | 0.574 events/year |
| Triheptanoin-Naïve Cohort | Annualized Event Rate of Rhabdomyolysis MCEs | 0.281 events/year |
Secondary
Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI)
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007-CL201-Rollover Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 12 | -5.27 g/m | Standard Deviation 21.433 |
| UX007-CL201-Rollover Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 24 | -2.73 g/m | Standard Deviation 23.711 |
| UX007-CL201-Rollover Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 36 | -6.75 g/m | Standard Deviation 28.933 |
| UX007-CL201-Rollover Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 48 | -12.33 g/m | Standard Deviation 29.263 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 24 | -0.37 g/m | Standard Deviation 18.132 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 36 | 1.23 g/m | Standard Deviation 19.488 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 60 | 8.83 g/m | Standard Deviation 25.639 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 12 | 4.55 g/m | Standard Deviation 21.903 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 48 | -1.04 g/m | Standard Deviation 21.9 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 24 | 1.00 g/m | Standard Deviation 39.459 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 48 | -9.67 g/m | Standard Deviation 36.529 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 12 | -9.06 g/m | Standard Deviation 29.965 |
| Triheptanoin-Naïve Cohort | Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI) | Change at Month 36 | 12.33 g/m | Standard Deviation 38.831 |
Secondary
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD)
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 48 | 10.88 mm | Standard Deviation 17.264 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 12 | 2.19 mm | Standard Deviation 9.138 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 36 | -0.11 mm | Standard Deviation 13.174 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 24 | 3.26 mm | Standard Deviation 11.158 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 36 | 3.23 mm | Standard Deviation 8.883 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 12 | 2.38 mm | Standard Deviation 8.719 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 24 | 3.00 mm | Standard Deviation 8.535 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 48 | 3.82 mm | Standard Deviation 9.115 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 60 | 40.29 mm | Standard Deviation 5.407 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 12 | 1.57 mm | Standard Deviation 4.308 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 60 | 50.00 mm | — |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 48 | 2.60 mm | Standard Deviation 5.177 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 24 | 0.67 mm | Standard Deviation 4.755 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD) | Change at Month 36 | 4.78 mm | Standard Deviation 5.094 |
Secondary
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline, Month 12, Month 18, Month 24, Month 30, Month 36, Month 48, Month 60
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 24 | -1.86 percent of blood ejected during systole | Standard Deviation 9.062 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 12 | 0.76 percent of blood ejected during systole | Standard Deviation 7.602 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 30 | 0.00 percent of blood ejected during systole | — |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 48 | -1.33 percent of blood ejected during systole | Standard Deviation 3.445 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 36 | -1.10 percent of blood ejected during systole | Standard Deviation 7.259 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 60 | -5.00 percent of blood ejected during systole | Standard Deviation 7.394 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 12 | 1.32 percent of blood ejected during systole | Standard Deviation 7.254 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 24 | 0.24 percent of blood ejected during systole | Standard Deviation 8.875 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 36 | -1.92 percent of blood ejected during systole | Standard Deviation 5.986 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 48 | -1.57 percent of blood ejected during systole | Standard Deviation 7.464 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 48 | 1.60 percent of blood ejected during systole | Standard Deviation 5.459 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 36 | 3.44 percent of blood ejected during systole | Standard Deviation 7.601 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 12 | 0.71 percent of blood ejected during systole | Standard Deviation 6.474 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 60 | 1.00 percent of blood ejected during systole | — |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 24 | 2.31 percent of blood ejected during systole | Standard Deviation 8.4 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF) | Change at Month 18 | 0.00 percent of blood ejected during systole | — |
Secondary
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM)
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 12 | -1.50 g | Standard Deviation 29.374 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 24 | 9.71 g | Standard Deviation 27.034 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 36 | 6.21 g | Standard Deviation 30.355 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 48 | 33.25 g | Standard Deviation 12.842 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 24 | 5.61 g | Standard Deviation 34.465 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 36 | 16.36 g | Standard Deviation 36.898 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 60 | 46.29 g | Standard Deviation 19.102 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 12 | 12.58 g | Standard Deviation 22.648 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 48 | 19.72 g | Standard Deviation 42.645 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 24 | 3.25 g | Standard Deviation 38.833 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 48 | 10.25 g | Standard Deviation 52.753 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 12 | -0.75 g | Standard Deviation 25.935 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM) | Change at Month 36 | 15.75 g | Standard Deviation 48.922 |
Secondary
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF)
Fractional shortening is calculated by measuring the percentage change in left ventricular diameter during systole. A negative value indicates less ventricular/muscular contractility, and a positive value indicates more ventricular/muscular contractility.
Time frame: Baseline, Month 12, Month 24, Month 30, Month 36, Month 48, Month 60
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment. Participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 12 | -1.30 % change in left ventricular diameter | Standard Deviation 5.564 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 36 | -0.10 % change in left ventricular diameter | Standard Deviation 6.086 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 30 | -7.00 % change in left ventricular diameter | — |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 48 | 3.00 % change in left ventricular diameter | Standard Deviation 4.32 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 24 | -1.90 % change in left ventricular diameter | Standard Deviation 6.052 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 60 | -0.57 % change in left ventricular diameter | Standard Deviation 4.392 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 12 | -0.91 % change in left ventricular diameter | Standard Deviation 6.468 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 24 | 1.03 % change in left ventricular diameter | Standard Deviation 6.242 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 36 | 0.25 % change in left ventricular diameter | Standard Deviation 4.502 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 48 | 0.52 % change in left ventricular diameter | Standard Deviation 4.501 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 36 | 1.11 % change in left ventricular diameter | Standard Deviation 5.395 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 12 | -1.48 % change in left ventricular diameter | Standard Deviation 5.904 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 60 | 0.00 % change in left ventricular diameter | — |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 24 | -1.36 % change in left ventricular diameter | Standard Deviation 7.967 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF) | Change at Month 48 | -0.60 % change in left ventricular diameter | Standard Deviation 6.269 |
Secondary
Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants)
The Z-scores express the deviation (or how far away) the measure is from the mean LVEF based on the size or age of the pediatric participants: Z-score=0 indicates the participant is exactly the same as the mean of the healthy general population. Z-score=-1 indicates it's 1 standard deviation below the mean of the healthy population. Z-score=+1 indicates it's 1 standard deviation above the mean.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment. Pediatric participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Change at Month 12 | 0.34 Z-score | Standard Deviation 1.229 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Change at Month 24 | -0.05 Z-score | Standard Deviation 1.469 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Change at Month 24 | 2.28 Z-score | — |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Change at Month 12 | 1.84 Z-score | — |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Change at Month 36 | -0.52 Z-score | — |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Change at Month 24 | 0.72 Z-score | Standard Deviation 1.103 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Change at Month 36 | -0.66 Z-score | — |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants) | Change at Month 12 | 0.21 Z-score | Standard Deviation 1.492 |
Secondary
Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants)
The Z-scores express the deviation (or how far away) the measure is from the mean LVSF based on the size or age of the pediatric participants: Z-score=0 indicates the participant is exactly the same as the mean of the healthy general population. Z-score=-1 indicates it's 1 standard deviation below the mean of the healthy population. Z-score=+1 indicates it's 1 standard deviation above the mean.
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
Population: Full Analysis Set: all participants enrolled who had at least 1 post-baseline efficacy assessment. Pediatric participants with a value at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 12 | 0.10 Z-score | Standard Deviation 1.659 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 24 | 0.27 Z-score | Standard Deviation 2.255 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 36 | 0.75 Z-score | Standard Deviation 1.729 |
| UX007-CL201-Rollover Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 48 | 0.53 Z-score | Standard Deviation 0.316 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 24 | 0.30 Z-score | Standard Deviation 1.607 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 36 | 0.13 Z-score | Standard Deviation 1.115 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 60 | -0.45 Z-score | Standard Deviation 0.834 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 12 | 0.25 Z-score | Standard Deviation 1.315 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 48 | 0.24 Z-score | Standard Deviation 1.464 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 24 | 0.13 Z-score | Standard Deviation 2.119 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 48 | 0.10 Z-score | Standard Deviation 1.888 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 12 | -0.38 Z-score | Standard Deviation 1.597 |
| Triheptanoin-Naïve Cohort | Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants) | Change at Month 36 | 0.58 Z-score | Standard Deviation 1.943 |