Safety, Tolerability and Effect of ARC-AAT Injection on Circulating and Intrahepatic Alpha-1 Antitrypsin Levels

NCT02900183 | Withdrawn Phase 2

• 2 other identifiers: ARCAAT20012016-000917-59
• Study Type: interventional
• Target: N/A
• Locations: 4 countries
• Sites: 4

Brief Summary

Patients with Alpha-1 Antitrypsin Deficiency (AATD) will be enrolled to receive multiple doses of ARC-AAT Injection. All subjects will require a pre-dose biopsy and a biopsy post last dose.

Conditions

Alpha-1 Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

• Incidence and frequency of adverse events as a measure of safety and tolerability of multiple doses of ARC-AAT Injection

  Baseline through Day 287 End-of Study Visit

Secondary Outcomes (1)

• Change from baseline in circulating serum levels of alpha-1 antitrypsin

  Baseline through Day 287 End-of Study Visit

Study Arms (1)

ARC-AAT Injection

EXPERIMENTAL

Intravenous administration of ARC-AAT Injection (4 mg/kg or 6 mg/kg) every 28 days for a total of 7 doses

Drug: ARC-AAT Injection

Interventions

ARC-AAT Injection DRUG

RNA interference (RNAi)-based, liver-targeted therapeutic

ARC-AAT Injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-nursing female patients 18-75 years of age, inclusive, at the time of Screening
• Previous diagnosis of PiZZ genotype Alpha-1 Antitrypsin Deficiency (AATD)
• Non-smoker (not a daily cigarette smoker) for at least three years with current non-smoking status confirmed by urine cotinine at screening.
• Highly effective, double barrier contraception (both male and female partners) during the study and for 3 months following the last dose of ARC-AAT Injection
• Suitable venous access for blood sampling

You may not qualify if:

• Known diagnosis of hepatic fibrosis from a cause other than AATD
• History of poorly controlled autoimmune disease, or any history of autoimmune hepatitis
• Human immunodeficiency virus (HIV) infection
• Seropositive for Hepatitis B virus (HBV) or Hepatitis C virus (HCV)
• Uncontrolled hypertension
• History of cardiac rhythm disturbances
• Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to study entry
• History of malignancy within the last 2 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer
• History of major surgery within 1 month of Screening
• Regular use of alcohol within one month prior to the Screening visit
• Use of illicit drugs (such as cocaine, phencyclidine \[PCP\] and crack) within 1 year prior to Screening or positive urine drug screen at Screening
• Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study involving a therapeutic intervention
• Any clinically significant history/presence of an uncontrolled systemic disease
• Blood donation (≥500 mL) within 7 days prior to study treatment administration

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (4)

Research Site 1

Toronto, Ontario, M5T3A9, Canada

Location

Research Site 2

Dublin, Ireland

Location

Research Site 3

Pavia, 27100, Italy

Location

Research Site 4

Malmo, SE-205 02, Sweden

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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 14, 2016
• Study Start: October 1, 2016
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1); IT (1); CA (1); SE (1)