Clinical Trials

Date: 2018-07-26

Type of information: Clinical trial authorisation

phase: 1-2

Announcement: treatment of the first patient

Company: Ultragenyx Pharmaceutical (USA - CA)

Product: DTX401

Action mechanism:

gene therapy. GSDIa is the most common genetically inherited glycogen storage disease. It is caused by a defective gene for the enzyme glucose-6-phosphatase-?(G6Pase-?), resulting in the inability to regulate glucose. Hypoglycemia in GSDIa patients can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, progress to renal failure, and potentially die in infancy or childhood. There are no approved pharmacological therapies. An estimated 6,000 patients worldwide are affected by GSDIa.
DTX401 is an investigational adeno-associated virus vector (AAV) type 8 gene therapy designed to deliver stable expression and activity of G6Pase-? following a single intravenous infusion and has been shown in preclinical studies to improve G6Pase-? activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression. DTX401 has been granted Orphan Drug Designation in both the United States and Europe.
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Disease: glycogen storage disease type Ia (GSDIa)

Therapeutic area: Rare diseases - Genetic diseases - Metabolic diseases

Country: USA

Trial details:

The primary objective of the study is to determine the safety of single doses of DTX401, including the incidence of dose-limiting toxicities (DLTs) at each dose level. The open-label, dose-finding Phase 1/2 study evaluates the safety, tolerability and therapeutic response of DTX401 in adults with GSDIa. Key efficacy assessments include time to hypoglycemia, impact on biomarkers such as lipids, uric acid, and measurement of glycogen in liver. There are three potential dosing cohorts in the study, and three patients will be enrolled in each cohort. Patients in the first cohort receive a single dose of DTX401 of 2.0 ×10¹² GC/kg. The decision to proceed to the next, higher dose cohort will be made after the data monitoring committee evaluates the safety data for all patients in the previous dosing cohort.(NCT03517085)

Latest news:

• On July 26, 2018, Ultragenyx Pharmaceutical announced that the first patient has been dosed in the Phase 1/2 study of DTX401, an adeno-associated virus vector based gene therapy for the treatment of patients with glycogen storage disease type Ia (GSDIa). Data from the three-patient first dose cohort are expected in the second half of 2018.
• On April 23, 2018, Ultragenyx Pharmaceutical announced that the FDA has cleared the Investigational New Drug (IND) application for DTX401, an adeno-associated virus vector based gene therapy for the treatment of glycogen storage disease type Ia (GSDIa). Enrollment in the Phase 1/2 study is expected to begin in the first half of 2018, with data from the first cohort expected in the second half of 2018.
The open-label, multicenter Phase 1/2 study will evaluate the safety, tolerability and therapeutic response of DTX401 in adults with GSDIa. Key efficacy assessments include time to hypoglycemia, impact on biomarkers such as lipids, uric acid, and measurement of glycogen in liver. There are three potential dosing cohorts in the study, and three patients will be enrolled in each cohort.