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

January 3, 2019 updated by: Alnylam Pharmaceuticals

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Sterile Normal Saline (0.9% NaCl)
Drug: Sterile Normal Saline (0.9% NaCl)
calculated volume to match active comparator
Active Comparator: ALN-AAT
Drug: ALN-AAT
Single or multiple doses of ALN-AAT by subcutaneous (sc) injection

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Profile of Pharmacokinetics (PK) of ALN-AAT
Time Frame: Part A (SAD) phase: up to 21 days; Part B (MAD) phase: up to 105 days; Part C: up to 161 days
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
The effect of ALN-AAT on serum levels of AAT protein
Time Frame: Part A (SAD) phase: through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224
Part A (SAD) phase: through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alnylam Pharmaceuticals

Investigators

  • Study Director: Patrick Haslett, MD, Alnylam Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 9, 2015

Primary Completion (Actual)

January 3, 2018

Study Completion (Actual)

January 3, 2018

Study Registration Dates

First Submitted

July 16, 2015

First Submitted That Met QC Criteria

July 18, 2015

First Posted (Estimate)

July 21, 2015

Study Record Updates

Last Update Posted (Actual)

January 7, 2019

Last Update Submitted That Met QC Criteria

January 3, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-AAT-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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