Audentes Therapeutics has started dosing patients in a Phase I/ II clinical trial of AT342 for treatment of Crigler-Najjar Syndrome, a rare monogenic disease characterised by severe levels of unconjugated bilirubin in the blood, and the risk of irreversible neurological damage and death.
VALENS trial is a multicentre, multinational, open-label, randomised, ascending dose study that seeks to examine the safety and efficacy of AT342 in 12 Crigler-Najjar patients, with the youngest a year old.
The study will comprise nine AT342 treated and three delayed-treatment concurrent control subjects.
Primary endpoints of VALENS feature safety such as adverse events and certain laboratory measures, including immunological parameters, as well as efficacy that will be expected to obtain through changes in serum bilirubin, and the number of hours on phototherapy within a 24-hour period.
During the trial, subjects are expected to remain on prescribed phototherapy for 12 weeks following administration of AT342, while those with a prespecified decrease in bilirubin at week 12 will be weaned off phototherapy over the subsequent five-week period.
Subjects are also expected to be followed for a minimum of five years to evaluate long-term safety and durability of effect.
Audentes Therapeutics senior vice-president and chief medical officer Suyash Prasad said: “Crigler-Najjar is a devastating rare disease characterised by severe jaundice, extremely high levels of unconjugated bilirubin in the blood, and the consequent risk of irreversible neurological damage and death.
“There are no approved products to treat Crigler-Najjar.
“The current standard of care requires most patients to spend more than ten to 12 hours per day under phototherapy lights, and natural history data from our LUSTRO run-in study demonstrates that even with this burdensome treatment, bilirubin may only be reduced to levels just below those considered to be neurotoxic.”
Audentes expects to receive preliminary data from VALENS by the second quarter of this year.