Safety, Tolerability and Effect on Liver Histologic Parameters of ARO-AAT

Purpose

The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, tolerability and effect on liver histologic parameters with administration of the investigational product, ARO-AAT, in participants with alpha-1 antitrypsin deficiency (AATD). Participants will receive multiple subcutaneous doses of ARO-AAT.

Condition

  • Alpha 1-Antitrypsin Deficiency

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Diagnosis of AATD
  • Liver biopsy at Screening indicating liver fibrosis
  • Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements
  • Non-smoker for at least 1 year
  • No abnormal finding of clinical relevance at Screening

Exclusion Criteria

  • Clinically significant health concerns other than AATD
  • Previous diagnosis or diagnosis at Screening of definitive liver cirrhosis
  • Previous lung or liver transplant due to AATD
  • Regular use of alcohol within one month prior to Screening
  • Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study involving therapeutic intervention
  • Use of illicit drugs within 1 year prior to Screening

NOTE: additional inclusion/exclusion criteria may apply, per protocol

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
ARO-AAT
Part A: administered on Days 1, 29 and 113 and every 84 days thereafter until dose selected for Part B Part B: minimum of 6, maximum of 9 doses
  • Drug: ARO-AAT Injection
    solution for subcutaneous (sc) injection
Placebo Comparator
Placebo
Part A: administered on Days 1, 29 and 113 and every 84 days thereafter until dose selected for Part B Part B: minimum of 6, maximum of 9 doses
  • Other: Placebo
    sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection

Recruiting Locations

University of Alabama at Birmingham Medical Center
Birmingham, Alabama 35233
Contact:
Rakesha Garner
205-934-1224
rgarner@uabmc.edu

More Details

Status
Recruiting
Sponsor
Arrowhead Pharmaceuticals

Study Contact

Medical Monitor
626-304-3400
medicalmonitor@arrowheadpharma.com

Detailed Description

In Part A, participants will be enrolled to receive multiple doses of ARO-AAT or placebo at varying dose levels. Once Part A is complete, a single dose level for Part B will be selected based on safety and pharmacodynamic parameters from Part A. Patients enrolled into Part A will roll over to the Part B dose level or continue to receive placebo.