US-based biopharmaceutical firm Arrowhead has commenced its Phase II clinical trial of ARC-AAT to treat liver disease associated with alpha-1 antitrypsin deficiency (AATD).
ARC-AAT is characterised by an unlocked nucleobase analog (UNA) containing RNAi trigger molecule for a systemic delivery using the Dynamic Polyconjugate delivery system.
It has proven its efficacy in affecting the Alpha-1 antitrypsin (AAT) gene transcript while decreasing the hepatic production of the mutant AAT (Z-AAT) protein in animal models.
The inflammatory Z-AAT protein is considered to be responsible for the cause of progressive liver disease in AATD patients.
The Phase II ARC-AAT trial has been designed as a multi-centre, open-label, multiple dose-escalation study of ARC-AAT and will include 12 participants.
It is intended to test the safety, efficacy and tolerability of multiple doses of ARC-AAT in treating AATD.
ARC-AAT will be administered in two dose levels and evaluated in two separate cohorts.
The subjects will receive a pre-dose biopsy, administered with seven doses of ARC-AAT and a post-dose biopsy after the 183rd day.
Arrowhead research and development CEO and head Bruce Given said: "There remains no medical treatment for the liver disease associated with AATD, which is increasingly being recognised by patients and physicians as a serious problem.
“Our Phase II 2001 study should give us, and the AATD community in general, the first insights into whether ARC-AAT can stop the progression of liver disease and possibly even allow the liver to recover and heal existing damage.
“This would be a significant breakthrough for patients."
The company is currently conducting a Phase I clinical trial of ARC-AAT with Part A involving healthy volunteers and Part B involving AATD patients.