A 2-Part Safety and Tolerability Study of ALN-AAT02 in HV and Patients
Research type
Research Study
Full title
A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Single-ascending and Multiple-dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-AAT02 in Healthy Adult Subjects and Patients with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
IRAS ID
255357
Contact name
Jorg Taubel
Contact email
Sponsor organisation
Alnylam Pharmaceuticals
Eudract number
2018-001362-41
Duration of Study in the UK
3 years, 4 months, 0 days
Research summary
We are conducting a clinical trial with a new medication called, ALN-AAT02 which has been developed as treatment for an inherited and currently incurable disease called alpha-1 antitrypsin deficiency (AATD).
People with AATD produce an abnormal form of a protein called alpha-1 antitrypsin (AAT) in their body. People with a severe form of this disease, called PiZZ AATD, accumulate abnormal AAT in their liver. This leads to severe liver disease, a high risk of developing liver cancer, and in many cases requires liver transplantation.
ALN-AAT02 has been effective at stopping the liver damage caused by AATD when tested in the laboratory and in animals. It works by reducing the production of AAT in the liver. It has been well-tolerated at low and high doses with no specific safety concerns in animals.The purposes of this study are to investigate: the safety of ALN-AAT02; how the body processes ALN-AAT02; and, in PiZZ AATD patients only, investigate the effect of ALN-AAT02 on liver disease.
The study will take place in two parts: part A and part B.
In part A, up to 64 healthy volunteers will be recruited into six groups (cohorts). In each cohort, 6 subjects will be randomly assigned to receive a single dose of ALN-AAT02, and 2 will receive placebo. Volunteers will be admitted to the research unit on Day -1, dosed on Day 1, and discharged on Day 2.
In part B, up to 32 PiZZ AATD patients will be recruited into two cohorts. In each cohort, 6 subjects will be randomly assigned to receive multiple doses of ALN-AAT02, and 2 subjects will receive multiple doses of placebo, over 12 weeks.
The dose of ALN-AAT02 will increase for each cohort if study investigators, after reviewing the safety data from the previous cohort, agree it is safe to do.
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
18/SC/0605
Date of REC Opinion
3 Dec 2018
REC opinion
Further Information Favourable Opinion