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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

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Sex
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 25 mg DB/200 mg OL 		Double-blind (DB) Period: 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. Open-label (OL) Period: Participants with fibrosis at Screening who received double-blind (DB) fazirsiran 25 mg and who completed the post-dose liver biopsy at Week 48 (or Week 72 or Week 96) entered the open-label phase and received fazirsiran 200 mg every 12 weeks for the duration of the study.
  • Drug: Fazisiran Injection
    solution for subcutaneous (sc) injection
    Other names:
    • ARO-AAT Injection
    • TAK-999 Injection
Experimental
Fazirsiran 100 mg DB/200 mg OL 		DB Period: Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. OL Period: Participants with fibrosis at Screening who received double-blind (DB) fazirsiran 100 mg and who completed the post-dose liver biopsy at Week 48 (or Week 72 or Week 96) entered the open-label phase and received fazirsiran 200 mg every 12 weeks for the duration of the study.
  • Drug: Fazisiran Injection
    solution for subcutaneous (sc) injection
    Other names:
    • ARO-AAT Injection
    • TAK-999 Injection
Experimental
Fazirsiran 200 mg DB/200 mg OL 		DB Period: Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. OL Period: Participants with fibrosis at Screening who received double-blind (DB) fazirsiran 200 mg and who completed the post-dose liver biopsy at Week 48 (or Week 72 or Week 96) entered the open-label phase and received fazirsiran 200 mg every 12 weeks for the duration of the study
  • Drug: Fazisiran Injection
    solution for subcutaneous (sc) injection
    Other names:
    • ARO-AAT Injection
    • TAK-999 Injection
Placebo Comparator
Placebo DB / Fazirsiran 200 mg OL 		DB Period: Participants with no fibrosis: Placebo administered on Day 1 and Week 4. Participants with fibrosis: Placebo administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. OL Period: Participants with fibrosis at Screening who received double-blind (DB) placebo and who completed the post-dose liver biopsy at Week 48 (or Week 72 or Week 96) entered the open-label phase and received fazirsiran 200 mg every 12 weeks for the duration of the study.
  • Drug: Fazisiran Injection
    solution for subcutaneous (sc) injection
    Other names:
    • ARO-AAT Injection
    • TAK-999 Injection
  • Other: Placebo
    sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.