Date: 2018-02-12
Type of
information: Treatment of the first patient
phase: 1-2
Announcement: treatment of the first patient
Company: Audentes Therapeutics (USA - CA)
Product: AT342
Action
mechanism:
- gene therapy. AT342 is an AAV vector containing a functional version of the UGT1A1 gene. Preclinical data in murine models of the disease demonstrate AAV-UGT1A1 significantly reduces bilirubin levels, even at UGT1A1 liver expression levels of just five to eight percent of normal.
- AT342 has been developed in collaboration with the University of Pennsylvania (Penn) under the leadership of James M. Wilson, M.D., Ph.D., a pioneer in human gene therapy and the director of the Gene Therapy Program and the Orphan Disease Center at the Perelman School of Medicine. As part of the collaboration, Penn has licensed certain Penn-owned AAV technologies to Audentes, including rights related to AT342.
- The FDA has granted Rare Pediatric Disease and Fast Track designations for AT342.
Disease: Crigler-Najjar Syndrome
Therapeutic
area: Rare diseases - Genetic diseases - Hepatic diseases - Liver diseases
Country: France, Germany, UK, USA
Trial
details:
- VALENS is designed as a multicenter, multinational, open-label, ascending dose study to evaluate the safety and preliminary efficacy of AT342 in approximately 12 Crigler-Najjar patients greater than or equal to one year of age. The study is expected to include nine AT342 treated subjects and three delayed-treatment concurrent control subjects. Primary endpoints include safety (adverse events and certain laboratory measures, including immunological parameters) and efficacy (changes in serum bilirubin and number of hours on phototherapy within a 24-hour period). Secondary endpoints include the proportion of subjects successfully weaned off phototherapy, and UGT protein expression, DNA and RNA levels from liver biopsy at 24 weeks. Subjects are expected to remain on prescribed phototherapy for 12 weeks following administration of AT342. Subjects with a meaningful decrease in bilirubin at week 12 will be weaned off phototherapy over a five-week period, starting in week 13 and ending during week 17. The primary efficacy analyses are expected to be conducted at the 12 and 18 -week time points. Subjects are expected to be followed for a minimum of five years to assess long term safety and durability of effect.
- (NCT03223194)
- In addition to VALENS, the clinical development program for AT342 includes LUSTRO, a prospective natural history run-in study in Crigler-Najjar patients. The primary objectives of LUSTRO are to characterize the disease course and natural history of Crigler-Najjar, assess the burden of disease on patients and caregivers, identify subjects for potential enrollment in VALENS, and serve as a longitudinal baseline and within-patient control for VALENS.
Latest
news:
- • On February 12, 2018, Audentes Therapeutics announced it has commenced dosing of patients in VALENS, a Phase 1 / 2 clinical trial of its product candidate AT342 for the treatment of Crigler-Najjar Syndrome. Audentes expects preliminary data from VALENS to be available in the second quarter of 2018.
- • On November 13, 2017, Audentes Therapeutics announced that the Medicines and Healthcare Products Regulatory Agency (MHRA) has approved the Clinical Trial Authorisation (CTA) application for AT342, its gene therapy product candidate being developed to treat Crigler-Najjar Syndrome. This is the first European CTA approval for the AT342 program, and it allows Audentes to initiate the enrollment process at clinical sites in the UK for VALENS, the Phase 1 / 2 clinical study of AT342.
- • On February 1, 2017, Audentes Therapeutics announced that the FDA has cleared the investigational new drug (IND) application for AT342, the company's gene therapy product candidate to treat Crigler-Najjar Syndrome. The IND is now active and Audentes plans to initiate VALENS, the multicenter, multinational, open-label, ascending dose phase 1 / 2 clinical study of AT342. Preliminary data from VALENS is expected to be available by the end of 2017.
- In addition to VALENS, Audentes plans to imminently begin LUSTRO, a clinical assessment and run-in study. LUSTRO is designed to enroll 16 to 18 Crigler-Najjar patients greater than one year of age and to characterize their disease course, natural history, bilirubin variability and phototherapy usage. The study is intended to identify patients for potential enrollment in VALENS and to serve as a within-patient control for VALENS.
Is
general: Yes
