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

NCT ID: NCT03945292

Last Updated: 2025-11-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-07

Study Completion Date

2023-09-18

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Alpha 1-Antitrypsin Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Fazisiran Injection

Intervention Type DRUG

solution for subcutaneous (sc) injection

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.

Group Type EXPERIMENTAL

Fazisiran Injection

Intervention Type DRUG

solution for subcutaneous (sc) injection

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

Group Type EXPERIMENTAL

Fazisiran Injection

Intervention Type DRUG

solution for subcutaneous (sc) injection

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.

Group Type PLACEBO_COMPARATOR

Fazisiran Injection

Intervention Type DRUG

solution for subcutaneous (sc) injection

Placebo

Intervention Type OTHER

sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection

Interventions

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Fazisiran Injection

solution for subcutaneous (sc) injection

Intervention Type DRUG

Placebo

sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection

Intervention Type OTHER

Other Intervention Names

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ARO-AAT Injection TAK-999 Injection

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Arrowhead Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site 5

Birmingham, Alabama, United States

Site Status

Research Site 9

Phoenix, Arizona, United States

Site Status

Research Site 14

La Jolla, California, United States

Site Status

Research Site 17

Los Angeles, California, United States

Site Status

Research Site 11

Sacramento, California, United States

Site Status

Research Site 15

San Francisco, California, United States

Site Status

Research Site 13

Stanford, California, United States

Site Status

Research Site 2

Gainesville, Florida, United States

Site Status

Research Site 7

Indianapolis, Indiana, United States

Site Status

Research Site 3

Iowa City, Iowa, United States

Site Status

Research Site 10

St Louis, Missouri, United States

Site Status

Research Site 12

New York, New York, United States

Site Status

Research Site 1

Charleston, South Carolina, United States

Site Status

Research Site 4

Nashville, Tennessee, United States

Site Status

Research Site 19

Houston, Texas, United States

Site Status

Research Site 16

Salt Lake City, Utah, United States

Site Status

Research Site 27

Aachen, , Germany

Site Status

Research Site 22

Pavia, , Italy

Site Status

Research Site 23

Leiden, , Netherlands

Site Status

Research Site 24

Funchal, , Portugal

Site Status

Research Site 20

Barcelona, , Spain

Site Status

Countries

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United States Germany Italy Netherlands Portugal Spain

References

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Clark VC, Strange C, Strnad P, Sanchez AJ, Kwo P, Pereira VM, van Hoek B, Barjaktarevic I, Corsico AG, Pons M, Goldklang M, Gray M, Kuhn B, Vargas HE, Vierling JM, Vuppalanchi R, Brantly M, Kappe N, Chang T, Schluep T, Zhou R, Hamilton J, San Martin J, Loomba R. Fazirsiran for Adults With Alpha-1 Antitrypsin Deficiency Liver Disease: A Phase 2 Placebo Controlled Trial (SEQUOIA). Gastroenterology. 2024 Oct;167(5):1008-1018.e5. doi: 10.1053/j.gastro.2024.06.028. Epub 2024 Jul 2.

Reference Type DERIVED
PMID: 38964420 (View on PubMed)

Remih K, Amzou S, Strnad P. Alpha1-antitrypsin deficiency: New therapies on the horizon. Curr Opin Pharmacol. 2021 Aug;59:149-156. doi: 10.1016/j.coph.2021.06.001. Epub 2021 Jul 10.

Reference Type DERIVED
PMID: 34256305 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-003385-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AROAAT2001

Identifier Type: -

Identifier Source: org_study_id

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