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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Alnylam Pharmaceuticals Identifier:
First received: July 16, 2015
Last updated: May 13, 2016
Last verified: May 2016
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.

Condition Intervention Phase
Antitrypsin Deficiency Liver Disease
Drug: Sterile Normal Saline (0.9% NaCl)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Participant)
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Alnylam Pharmaceuticals:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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

  • 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 ]

Estimated Enrollment: 66
Study Start Date: July 2015
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ALN-AAT Drug: ALN-AAT
Single or multiple doses of ALN-AAT by subcutaneous (sc) injection
Placebo Comparator: Sterile Normal Saline (0.9% NaCl) Drug: Sterile Normal Saline (0.9% NaCl)
calculated volume to match active comparator


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT02503683

United Kingdom
Richmond Pharmacology, Ltd.
London, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Study Director: Patrick Haslett, MD Alnylam Pharmaceuticals
  More Information

Responsible Party: Alnylam Pharmaceuticals Identifier: NCT02503683     History of Changes
Other Study ID Numbers: ALN-AAT-001
Study First Received: July 16, 2015
Last Updated: May 13, 2016

Keywords provided by Alnylam Pharmaceuticals:
RNAi therapeutic
Alpha-1 Antitrypsin Deficiency

Additional relevant MeSH terms:
Liver Diseases
Alpha 1-Antitrypsin Deficiency
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Pathologic Processes
Alpha 1-Antitrypsin
Protein C Inhibitor
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on May 25, 2017