A Study of an Investigational Drug, ALN-AAT, in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease

Antitrypsin Deficiency Liver Disease Clinical Trial

Official title:

A Phase 1/2, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02503683
• Other study ID #: ALN-AAT-001
• Status: Terminated
• Phase: Phase 1
• Start date: July 9, 2015
• Est. completion date: January 3, 2018

Study information

• Verified date: January 2019
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered ALN-AAT in Healthy Adult Subjects and Patients with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: January 3, 2018
• Est. primary completion date: January 3, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adequate complete blood counts, liver and renal function.

• 12-lead electrocardiogram (ECG) within normal limits

• Female subjects must be of non-childbearing potential; e.g. post-menopausal or pre-menopausal with surgical sterilization

• Male subjects agree to use appropriate contraception

• Willing to provide written informed consent and willing to comply with study requirements

• Nonsmokers for at least 5 years before screening

Exclusion Criteria:

• Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk

• Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study

• Active serious mental illness or psychiatric disorder requiring current pharmacological intervention

• History or evidence of alcohol or drug abuse within 12 months before screening.

• History of intolerance to SC injection

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Antitrypsin Deficiency Liver Disease
• Liver Diseases

Intervention

Drug:
• ALN-AAT
Single or multiple doses of ALN-AAT by subcutaneous (sc) injection
• Sterile Normal Saline (0.9% NaCl)
calculated volume to match active comparator

Locations

Country	Name	City	State
United Kingdom	Richmond Pharmacology, Ltd.	London

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety of ALN-AAT evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation		Part A (SAD phase): through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224
Secondary	Profile of Pharmacokinetics (PK) of ALN-AAT	Cmax, tmax, AUC, t1/2	Part A (SAD) phase: up to 21 days; Part B (MAD) phase: up to 105 days; Part C: up to 161 days
Secondary	The effect of ALN-AAT on serum levels of AAT protein		Part A (SAD) phase: through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224