RNAi therapeutics firm Alnylam Pharmaceuticals is seeking approval from the UK Medicines and Healthcare products Regulatory Agency (MHRA) to start a Phase I/II clinical trial with ALN-AAT.
The company has filed a clinical trial application (CTA) with MHRA for ALN-AAT, which is a subcutaneously administered investigational RNAi therapeutic targeting alpha-1 antitrypsin (AAT) to treat AAT deficiency-associated liver disease (alpha-1 liver disease).
The intended clinical study of ALN-AAT will be carried out in normal healthy volunteers, and then in subjects with alpha-1 liver disease, as per the CTA filing.
With initial data expected to be reported in early 2016, the company plans to begin the study later this year following approval of the CTA.
Alnylam chief medical officer and R&D executive vice-president Dr Akshay Vaishnaw said: "We believe ALN-AAT holds considerable promise as a novel therapeutic approach for the treatment of alpha-1 liver disease, an increasingly recognised clinical manifestation of alpha-1-antitrypsin deficiency where there is a significant unmet need and where liver transplantation is the only available treatment option."
Designed to enrol up to a total of 48 healthy adult volunteers, the trial will be a randomised, single-blind and placebo-controlled study that will be carried out in three parts.
Parts A and B will be single-dose and multi-dose dose escalation studies, while part C will be a multi-dose study in adults with the PiZZ mutation in their AAT gene and with mild-to-moderate liver fibrosis.
According to the firm, the primary objective of the trial is to assess safety and tolerability of single and multiple subcutaneous doses of ALN-AAT and secondary objectives comprise evaluation of pharmacokinetics of ALN-AAT and clinical activity for ALN-AAT as measured by knockdown of serum AAT.
The company has presented a new pre-clinical data in an oral presentation at the Digestive Disease Week (DDW) meeting, which demonstrated a knockdown of serum AAT of up to 93% in non-human primates (NHPs) with monthly subcutaneous dosing and a wide therapeutic index.