臨床研究等提出・公開システム

A Randomized, Double-blind, Multicenter Study to Determine the Effect of Triheptanoin Compared with Even-chain Medium-chain Triglycerides (MCT) on Major Clinical Events (MCEs) in Pediatric Patients with Long-chain Fatty Acid Oxidation Disorders (LC-FAOD)

A Study to Determine the Effect of Triheptanoin Compared with Even-chain MCT on MCEs in Pediatric Patients with LC-FAOD

Kajiwara Makoto

PPD-SNBL K.K.

St. Lukes Tower, 8-1, Akashi-cho, Chuo-ku, Tokyo

CRGPPDSNBL-9-UX007-CL302_JPN_All@Thermofisher.com

Kajiwara Makoto

PPD-SNBL K.K.

St. Lukes Tower, 8-1, Akashi-cho, Chuo-ku, Tokyo

+81-80-6771-1846

CRGPPDSNBL-9-UX007-CL302_JPN_All@Thermofisher.com

Complete

Jan. 01, 2025

Interventional

non-randomized controlled trial

double blind

active control

parallel assignment

treatment purpose

1. Confirmed diagnosis of LC-FAOD: carnitine palmitoyl transferase (CPT) I deficiency, CPT II deficiency, carnitine/acylcarnitine translocase (CACT) deficiency, very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, or mitochondrial trifunctional protein (TFP) deficiency. Diagnosis must be confirmed by results of acylcarnitine profiles, fatty acid oxidation probe studies in cultured fibroblasts, or mutation analysis obtained from medical records
2. Males and females, from 0 (including newborns) to < 18 years of age
3. Have ANY ONE of the following significant clinical manifestations of LC-FAOD:
- At least 2 in the prior year, or 3 in the prior 2 years, of severe major episodes of metabolic decompensation (eg, hypoglycemia, rhabdomyolysis, or exacerbation of cardiomyopathy, requiring ER/urgent care unit visits or hospitalizations)
- Recurrent symptomatic hypoglycemia (clinical symptoms of hypoglycemia) requiring intervention
- Susceptibility to hypoglycemia after short periods of fasting (less than 4 to 12 hours, depending on age)
- Evidence of functional cardiomyopathy requiring ongoing medical management or clinical manifestation of heart failure
- Sibling(s) with the same pathogenic variant who presented with MCEs
- Subject with pathogenic variants that are known or suspected to be associated with absent or severely reduced enzyme activity or with severe disease manifestations

Note: Additional inclusion/exclusion criteria may apply, per protocol.

1. Treatment with triheptanoin within 60 days of Screening
2. History of known hypersensitivity to triheptanoin or MCT
3. Have any comorbid 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 interpretation of results. History of metabolic decompensation(s) with metabolic acidosis, hyperammonemia, and/or liver enzyme elevations does not constitute an exclusion criterion unless 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 interpretation of results.
4. Have a diagnosis of pancreatic insufficiency

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Both

Long-chain Fatty Acid Oxidation Disorders

Subjects receive Triheptanoin or MCT oil orally or via enteral feeding tube at least 4 times per day.

- Annualized event rate of MCEs

- Annualized duration of MCEs
- Annualized hypoglycemic event-rate captured as MCEs and HCEs
- CGI-C scale score
- Left ventricular ejection fraction, left ventricular systolic volume, and left ventricular wall mass
- Change from baseline to 6 months in hepatic PDFF%, assessed by 1H-MRS in subjects enrolled in the Liver Substudy
- Annualized frequency and duration of rhabdomyolysis MCEs
- Annualized frequency and duration of cardiomyopathy MCEs
- Annualized duration of hypoglycemic-MCEs
- Change from baseline in scores for:
- Caregiver-reported PedsQL 4.0 Generic Core Scale (physical health summary, psychosocial health summary, and total scores) (2 years of age and older)
OR
- PedsQL Infant Scale (physical health summary, psychosocial health summary, and total scores) (ages 1 to < 24 months)
- Survival time - Annualized hospitalization days
- Number of missed school or learning opportunity days
- Frequency, severity, and relationship to study drug of TEAEs, serious TEAEs, and AESIs
- Incidence of TEAEs and serious TEAEs leading to dose modifications, dose reductions, treatment interruptions, discontinuations from study drug, and discontinuations from the study
- Plasma concentration levels of heptanoate and beta-hydroxy pentanoate (BHP)
- Acceptability and Palatability Survey scores of triheptanoin mixed with oral liquids

+81-3-3813-3111

Nov. 29, 2024

No

Czech Republic/Germany/Poland/Saudi Arabia/Spain/Turkey/United Kingdom