NCT02363946

A Study of ARC-AAT in Healthy Volunteer Subjects and Patients With Alpha-1 Antitrypsin Deficiency (AATD)

A Double-Blind, Placebo-Controlled, Dose-Escalating, Phase 1 Study to Determine the Safety, Tolerability, Pharmacokinetics and Effect of Circulating Alpha-1 Antitrypsin Levels of ARC-AAT in Healthy Volunteer Subjects and in Patients With Alpha-1 Antitrypsin Deficiency (AATD)

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 65 (actual)
• Sponsor: Arrowhead Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

The purpose of the study is to determine the safety and tolerability of escalating doses of ARC-AAT and to evaluate the pharmacokinetics of ARC-AAT and the effect of ARC-AAT on circulating levels of alpha-1 antitrypsin (AAT). The study will consist of two parts, Part A (conducted in healthy volunteers) and Part B (conducted in AATD patients) at up to 9 escalating dose levels with 6 participants per dose level.

Detailed description

Healthy volunteers and AATD patients will be randomized to receive a single intravenous injection of either ARC-AAT or Placebo in double-blind fashion. Up to thirteen cohorts (6 participants per cohort) will be enrolled. Participants in all cohorts will be confined to the clinical facility beginning on Day -1 with discharge on Day 2. Escalation to the next dose level will proceed until a participant experiences a dose-limiting toxicity (DLT) or there is achievement of pre-determined threshold reductions in AAT levels. Dosing in participants with AATD will commence based on pre-determined threshold reductions in AAT levels for healthy volunteers. For each participant, the duration of the study clinic visits is up to 11 weeks, from Screening to the End-of-Study examination. However, including a Day 90 Follow-Up telephone call, the maximum study duration is approximately 20 weeks.

Conditions

• Alpha-1 Antitrypsin Deficiency

Interventions

Type	Name	Description
DRUG	ARC-AAT Injection	RNA interference-based, liver-targeted therapeutic
OTHER	Placebo	0.9 % normal saline
DRUG	Diphenhydramine	Diphenhydramine 50 mg p.o. was administered 2 hours (±30 minutes) pre-dose as antihistamine pre-treatment.

Timeline

• Start date: 2015-02-01
• Primary completion: 2016-11-01
• Completion: 2016-11-01
• First posted: 2015-02-16
• Last updated: 2026-01-12
• Results posted: 2018-08-03

Locations

4 sites across 4 countries: Australia, Germany, Netherlands, United Kingdom