Phase 2 N=29 Treatment

A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)

Long-chain Fatty Acid Oxidation Disorders (LC-FAOD) · Carnitine Palmitoyltransferase (CPT II) Deficiency · Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency · Longchain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency · Trifunctional Protein (TFP) Deficiency

Bottom Line

View on ClinicalTrials.gov: NCT01886378 ↗

Enrolled (actual)

Serious AEs

65.5%

Results posted

Feb 2021

Primary outcome: Primary: Change From Baseline in Time Adjusted-Area Under the Curve (AUC/Time) for Workload During Cycle Ergometry at Week 24 — 423.594 watts — p=0.1518

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: UX007 (Drug)
Age: Pediatric, Adult, Older Adult · 0+ yrs
Sex: All
Sponsor: Ultragenyx Pharmaceutical Inc
Primary completion: Aug 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Time Adjusted-Area Under the Curve (AUC/Time) for Workload During Cycle Ergometry at Week 24	423.594	0.1518
PRIMARY Change From Baseline in Time-Adjusted-AUC for Respiratory Exchange Ratio (RER) During Cycle Ergometry at Week 24	-0.011	0.3964
PRIMARY Change From Baseline in Actual Duration of Exercise During Cycle Ergometry at Week 24	4.671	0.0777
PRIMARY Change From Baseline in Distance Traveled During the 12-Minute Walk Test (12MWT) at Week 18	181.37	0.0830
PRIMARY Change From Baseline in Energy Expenditure Index (EEI) During the 12MWT at Week 18	-0.185	0.0320 sig
PRIMARY Change From Baseline in Percentage of the Predicted 6-Minute Walk Test (6MWT) Distance Walked at Week 18	12.44	0.0850
PRIMARY Change From Baseline in Physical Summary Score (PHS-10) of the Short Form 10 (SF-10) at Week 24	2.16	0.3754
PRIMARY Change From Baseline in Psychosocial Summary Score (PSS-10) of the SF10 at Week 24	0.816	0.7564
PRIMARY Change From Baseline in the Physical Component Summary Scale (PCS-12) at Week 24	8.88	<0.0001 sig
PRIMARY Change From Baseline in the Mental Component Summary Scale (MCS-12) at Week 24	9.7	0.0152 sig
PRIMARY Annualized Event Rate of All Major Clinical Events Pre- and Post-Treatment With UX007	1.69; 0.877	—
PRIMARY Annualized Duration Rate of All Major Clinical Events Pre- and Post-Treatment With UX007	5.961; 2.964	—
PRIMARY Annualized Event Rate of Major Rhabdomyolysis Clinical Events Pre- and Post-Treatment With UX007	1.303; 0.833	—
PRIMARY Annualized Duration Rate of Major Rhabdomyolysis Clinical Events Pre- and Post-Treatment With UX007	3.949; 2.792	—
PRIMARY Annualized Event Rate of Major Hypoglycemia Clinical Events Pre- and Post-Treatment With UX007	0.318; 0.023	—
PRIMARY Annualized Duration Rate of Major Hypoglycemia Clinical Events Pre- and Post-Treatment With UX007	1.414; 0.023	—
PRIMARY Annualized Event Rate of Major Cardiac Clinical Events Pre- and Post-Treatment With UX007	0.069; 0.021	—
PRIMARY Annualized Duration Rate of Major Cardiac Clinical Events Pre- and Post-Treatment With UX007	0.598; 0.149	—

Summary

The primary objective of the study was to evaluate the impact of UX007 on acute clinical pathophysiology associated with LC-FAOD following 24 weeks of treatment.

Eligibility Criteria

Inclusion Criteria

Confirmed diagnosis of CPT II, VLCAD, LCHAD, or TFP deficiency, based on results of acylcarnitine profiles, fatty acid oxidation probe studies in cultured fibroblasts, and/or mutation analysis obtained from medical records.
Male or female, at least 6 months of age
Willing and able to complete all aspects of the study through the end of the study. If a minor, have a caregiver(s) willing and able to assist in all applicable study requirements.
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
Willing and able to provide access to medical records charting the last 18-24 months of care prior to the study initiation, or from birth for those subjects less than 18 months of age
No history of serious adverse reactions or known hypersensitivity to triheptanoin
Currently managed on a stable treatment regimen (including diet), which may include low-fat/high-carbohydrate diet, avoidance of fasting, carnitine and/or medium-chain triglyceride (MCT) oil. The treatment regimen (including diet) should be stable for the last 60 days to assure that changes in the subject's condition are not confounded by recent changes in the treatment regimen that could affect the 4 week run-in evaluation period. Once study drug treatment has started, must be willing to maintain all aspects of the subject's treatment regimen and diet unchanged, other than discontinuation of MCT oil, in order to avoid potential variability of response due to variations in dietary intake.
Have severe LC-FAOD, as evidenced by ANY ONE of the following significant clinical manifestations despite therapy:
Chronic Elevated Creatine Kinase (CK) with Major Clinical Events: Elevated mean CK levels over the last 6 months -1 year (defined as ≥ 2X upper limit of age/gender-matched normal, or ≥ 500 units/L if age-matched reference not established) not associated with an acute rhabdomyolysis event, AND at least two major clinical events (as defined in the protocol) in the last year, or at least four major clinical events over the last two years,
Episodic Elevated CK with Reported Muscle Dysfunction: Episodes of elevated CK levels over the last 6 months -1 year (defined as ≥ 2X upper limit of age/gender-matched normal, or ≥ 500 units/L if age-matched reference is not established) not associated with an acute rhabdomyolysis event, AND patient report of frequent muscle fatigue, exercise intolerance, or limitation of exercise,
Highly Elevated CK but Asymptomatic: More seriously elevated mean CK levels (defined as ≥ 4X upper limit of age/gender-matched normal, or ≥ 1000 units/L if age-matched reference is not established) consistent with substantial chronic muscle rupture over the last 6 months-1 year, regardless of frequency of hospitalizations or ER events,
Frequent Severe Major Medical Episodes (at least 3 within the past year, or 5 within 2 years) of hypoglycemia, rhabdomyolysis, or exacerbation of cardiomyopathy [CM], requiring emergency room [ER]/acute care visits or hospitalizations,
Severe Susceptibility to Hypoglycemia (serum glucose <60 mg/dL) after short periods of fasting (less than 4-12 hours, depending on age), with at least 2 events in the last year that require ongoing prophylactic management, OR recurrent symptomatic hypoglycemia (blood glucose levels or clinical symptoms of hypoglycemia) at home requiring intervention ≥ 2 times per week,
Evidence of Functional Cardiomyopathy (with echocardiogram (ECHO) within past 90 days documenting poor ejection fraction [EF]) requiring ongoing medical management
Females who have reached menarche must have a negative pregnancy test at Screening. If sexually active, subject must be willing to use acceptable method of contraception and have additional pregnancy tests during the study.

Exclusion Criteria

Diagnosis of carnitine-acylcarnitin

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01886378). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.