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

Alnylam Pharmaceuticals1 site in 1 country26 target enrollmentJuly 9, 2015

ConditionsAntitrypsin Deficiency Liver Disease

InterventionsALN-AAT Sterile Normal Saline (0.9% NaCl)

DrugsALN-AAT Sterile Normal Saline (0.9% NaCl)

Overview

Phase: Phase 1
Intervention: ALN-AAT
Conditions: Antitrypsin Deficiency Liver Disease
Sponsor: Alnylam Pharmaceuticals
Enrollment: 26
Locations: 1
Primary Endpoint: 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
Status: Terminated
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

July 9, 2015

End Date

January 3, 2018

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Alnylam Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

ALN-AAT

Intervention: ALN-AAT

Sterile Normal Saline (0.9% NaCl)

Intervention: Sterile Normal Saline (0.9% NaCl)

Outcomes

Primary Outcomes

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

Time Frame: Part A (SAD phase): through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224

Secondary Outcomes

Profile of Pharmacokinetics (PK) of ALN-AAT(Part A (SAD) phase: up to 21 days; Part B (MAD) phase: up to 105 days; Part C: up to 161 days)
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)