8:07AM Alnylam Pharma initiates phase ii clinical trial with ALN-TTRsc; Pilot Phase II trial now open for enrollment for attr patients with familial amyloidotic cardiomyopathy or senile systemic amyloidosis (ALNY) 59.42 : Co announced that it has initiated a pilot Phase II study with ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting the transthyretin gene in development for the treatment of TTR-mediated amyloidosis (ATTR). The Phase II trial, which is now open for enrollment, is aimed at evaluating the tolerability and preliminary clinical activity of ALN-TTRsc in TTR cardiac amyloidosis patients with familial amyloidotic cardiomyopathy -- which is caused by autosomal dominant mutations in the TTR gene, or senile systemic amyloidosis (SSA) -- which is caused by idiopathic accumulation of wild-type TTR in the heart. The company expects to present data from the Phase II trial in late 2014, and assuming positive results, begin a Phase III trial in TTR cardiac amyloidosis patients by the end of 2014.
The Phase II trial is an open-label, multi-dose study of ALN-TTRsc, designed to enroll approximately 15 TTR cardiac amyloidosis patients with FAC or SSA. The primary objective of the study is to evaluate the general tolerability of ALN-TTRsc. Patients will receive 5 daily doses followed by 5 weekly doses of 5 mg/kg, with follow-up through Day 90; in the Phase I ALN-TTRsc study, this dose resulted in an up to 93% TTR knockdown and a mean nadir knockdown of approximately 88%, and was found to be generally safe and well tolerated. Secondary objectives include assessment of clinical activity as measured by knockdown of serum TTR levels and additional tests, such as cardiac imaging (including echocardiography and cardiac MRI), circulating cardiac biomarkers (NT-proBNP and troponins T and I), 6-minute walk test, New York Heart Association (NYHA) classification, and measures of heart failure symptoms and quality of life (Kansas City Cardiomyopathy Questionnaire and EQ-5D QOL). Patients completing the Phase II trial will be eligible to participate in an open-label extension (OLE) study for further assessment of general tolerability and clinical activity with long-term dosing; the ALN-TTRsc Phase II OLE study is expected to be initiated in mid-2014.
