PK & PD of ALN - AAT in healthy volunteers and liver disease patients
Research type
Research Study
Full title
A PHASE 1/2, RANDOMIZED, SINGLE-BLIND, PLACEBO-CONTROLLED SINGLE-ASCENDING AND MULTIPLE DOSE, SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS STUDY OF SUBCUTANEOUSLY ADMINISTERED ALN-AAT IN HEALTHY ADULT SUBJECTS AND PATIENTS WITH ZZ TYPE ALPHA-1 ANTITRYPSIN DEFICIENCY LIVER DISEASE
IRAS ID
180821
Contact name
Jorg Taubel
Contact email
Sponsor organisation
Alnylam Pharmaceuticals, Inc
Eudract number
2015-001297-18
Duration of Study in the UK
2 years, 1 months, 3 days
Research summary
We are conducting a clinical trial with an investigational medication known as ALN-AAT which is being developed for the treatment of patients with an inherited liver disease; for which there is no effective treatment.
The purpose of the study is to determine suitable doses and frequency of ALN-AAT to be given to patients suffering from Alpha-1 Antitrypsin Deficiency Liver Disease (AATD) caused by deficiency of an important liver protein known as alpha-1 antitrypsin (AAT) in the blood. People with AAT deficiency are able to produce this protein; however, the disease prevents it from entering the bloodstream and instead gets trapped and accumulates in the liver which may cause inflammation and lead to cirrhosis (irreversible liver damage) and cancer.
The study will be carried out in 3 parts, i.e. A Single Ascending Dose (SAD) in up to 24 healthy volunteers (Part A ), a Multiple Ascending Dosing (MAD) in up to 24 healthy volunteers (Part B) and multiple dosing (MD) in up to 18 patients with AATD (Part C).
We will measure ALN-AAT levels in the blood and urine after dosing (pharmacokinetics) and we will assess the safety of ALN-AAT and how well it is tolerated when it is injected under the skin (i.e. sub-cutaneously) as compared to placebo. We will also measure the effect of the study drug on blood AAT levels (pharmacodynamics) and there will be additional procedures for patients.The time commitment required from each volunteer is approximately 5, 8 and 13 months for parts A, B and C respectively.
The study will be conducted at Richmond Pharmacology Ltd. (Parts A and B) and other sites and is funded by Alnylam Pharmaceuticals Inc. (the sponsor), which is a biopharmaceutical company based in the USA.
REC name
London - London Bridge Research Ethics Committee
REC reference
15/LO/0774
Date of REC Opinion
29 Jun 2015
REC opinion
Further Information Favourable Opinion