Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT)

Purpose

The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, efficacy and tolerability of multiple doses of the investigational product, Fazirsiran Injection, administered subcutaneously to participants with alpha-1 antitrypsin deficiency (AATD).

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 (score less than F4); a patient with no fibrosis may participate based on a previous biopsy conducted within one year - 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
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
Fazirsiran (also referred to as TAK-999 or ARO-AAT)
Participants with no fibrosis: Administered on Day 1 and Week 4 Participants with fibrosis: Administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses.
  • Drug: Fazisiran Injection
    solution for subcutaneous (sc) injection
    Other names:
    • ARO-AAT Injection
    • TAK-999 Injection
Placebo Comparator
Placebo
Participants with no fibrosis: Administered on Day 1 and Week 4 Participants with fibrosis: Administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses.
  • Other: Placebo
    sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection
Experimental
Open-Label Fazisiran (also referred to as TAK-999 or ARO-AAT)
After all enrolled participants completed the Week 16 visit, an interim analysis was performed to select a single dose level (25, 100 or 200 mg) for the open-label phase of the study. Fazirsiran 200 mg was the selected dose and all participants with fibrosis at Screening who completed the post-dose liver biopsy at Week 48 (or Week 72 or 96) receive this dose every 12 weeks for the duration of the study (open-label phase).
  • Drug: Fazisiran Injection
    solution for subcutaneous (sc) injection
    Other names:
    • ARO-AAT Injection
    • TAK-999 Injection

More Details

Status
Completed
Sponsor
Arrowhead Pharmaceuticals

Study Contact

Detailed Description

Participants will be enrolled to receive multiple subcutaneous injections of Fazirsiran Injection (also referred to as TAK-999 Injection or ARO-AAT Injection) or placebo. Eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. However, any participant with a biopsy result within 1 year of screening showing no fibrosis does not require a pre-dose biopsy. Only participants who have liver fibrosis will undergo a post-dose biopsy and may continue treatment in an open-label phase.