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

NCT02503683 | Terminated Phase 1

• 1 other identifier: ALN-AAT-001
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Antitrypsin Deficiency Liver Disease

Keywords

RNAi therapeutic; AAT; Alpha-1 Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (2)

ALN-AAT

ACTIVE COMPARATOR

Drug: ALN-AAT

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR

Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

ALN-AAT DRUG

Single or multiple doses of ALN-AAT by subcutaneous (sc) injection

ALN-AAT

Sterile Normal Saline (0.9% NaCl) DRUG

calculated volume to match active comparator

Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adequate complete blood counts, liver and renal function.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (1)

Richmond Pharmacology, Ltd.

London, United Kingdom

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Patrick Haslett, MD

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 21, 2015
• Study Start: July 9, 2015
• Primary Completion: January 3, 2018
• Study Completion: January 3, 2018
• Last Updated: January 7, 2019

Record last verified: 2019-01

Locations

GB (1)