US-based Ultragenyx Pharmaceutical has started patient enrolment in an open-label Phase II trial to evaluate safety and clinical effects of triheptanoin, also known as UX007, in patients severely affected by long-chain fatty acid oxidation disorders (LC-FAOD).
LC-FAOD is a group of autosomal recessive genetic disorders that are characterised by metabolic deficiencies in which the body is unable to breakdown and convert long chain fatty acids into energy.
Ultragenyx chief executive officer and president Emil Kakkis said: "The goal for this study is to determine the optimal patient population and endpoints for evaluation in a potential future Phase III clinical trial."
The prospective, interventional, open-label Phase II study will assess triheptanoin treatment in about 30 severely affected LC-FAOD patients, aged six months to 35 years, exhibiting significant clinical manifestations of LC-FAOD despite current therapy.
Before starting treatment with triheptanoin, patients will continue their current therapy for four weeks to establish their baseline condition, when the drug will be titrated to an expected target dose of 25%-35% of total daily caloric intake via oral administration, while ensuring tolerability.
The company said that the patients will be followed to assess the effects of triheptanoin treatment over 24 weeks, when it may continue treatment for an additional 54 weeks.
The trial will evaluate the impact of triheptanoin on several endpoints, including cycle ergometer performance, 12-minute walk test, muscle strength, creatine kinase levels, hypoglycemia, liver size, and cardiac disease.
The trial will be carried out at eight clinical sites in the US and Europe and its primary objective is to evaluate the impact of triheptanoin on acute clinical pathophysiology associated with LC-FAOD, while the secondary objectives are to assess the safety of triheptanoin treatment and its effects on energy metabolism in LC-FAOD patients.
According to the company, the objective of the extension period of the trial is to assess the impact of triheptanoin on major clinical events, including hospitalisations, emergency room visits, and emergency interventions associated with LC-FAOD.
Triheptanoin is a purified form of a specially designed synthetic triglyceride compound designed to provide patients with medium-length, odd-chain fatty acids that are metabolised to replace intermediate substrates in fatty acid oxidation downstream of their genetic block in fatty acid metabolism.
While there are six main genetic diseases that cause LC-FAOD, the company's main clinical programme is focused on the most common four forms: carnitine palmitoyltransferase II (CPT-II) deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, trifunctional protein deficiency (TFP), and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency.
Image: A mortality rate of more than 50% has been observed in LC-FAOD patients. Photo: courtesy of freedigitalphotos.net.