NCT03945292

Brief Summary

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).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Aug 2019

Typical duration for phase_2

Geographic Reach
6 countries

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 8, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 10, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

August 7, 2019

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 8, 2021

Completed
1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 18, 2023

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

December 30, 2024

Completed
Last Updated

November 4, 2025

Status Verified

October 1, 2025

Enrollment Period

2.3 years

First QC Date

May 8, 2019

Results QC Date

October 18, 2024

Last Update Submit

October 30, 2025

Conditions

Alpha 1-Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

  • Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16

    Baseline, Week 16 (+/- 2 weeks)

Secondary Outcomes (27)

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase

    Double Blind Phase (up to Week 48): dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase

    From dose administration of the first dose of open-label phase fazirsiran through EOS or Early Termination (up to Week 196).

  • Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis

    Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

  • Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis

    Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

  • Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis

    Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

  • +22 more secondary outcomes

Study Arms (4)

Fazirsiran 25 mg DB/200 mg OL

EXPERIMENTAL

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

Fazirsiran 100 mg DB/200 mg OL

EXPERIMENTAL

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

Fazirsiran 200 mg DB/200 mg OL

EXPERIMENTAL

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

Placebo DB / Fazirsiran 200 mg OL

PLACEBO COMPARATOR

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 InjectionOther: Placebo

Interventions

Fazisiran InjectionDRUG

solution for subcutaneous (sc) injection

Also known as: ARO-AAT Injection, TAK-999 Injection
Fazirsiran 100 mg DB/200 mg OLFazirsiran 200 mg DB/200 mg OLFazirsiran 25 mg DB/200 mg OLPlacebo DB / Fazirsiran 200 mg OL
PlaceboOTHER

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

Placebo DB / Fazirsiran 200 mg OL

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Research Site 5

Birmingham, Alabama, 35233, United States

Location

Research Site 9

Phoenix, Arizona, 85054, United States

Location

Research Site 14

La Jolla, California, 92037, United States

Location

Research Site 17

Los Angeles, California, 90095, United States

Location

Research Site 11

Sacramento, California, 95817, United States

Location

Research Site 15

San Francisco, California, 94158, United States

Location

Research Site 13

Stanford, California, 94305, United States

Location

Research Site 2

Gainesville, Florida, 32610, United States

Location

Research Site 7

Indianapolis, Indiana, 46202, United States

Location

Research Site 3

Iowa City, Iowa, 52242, United States

Location

Research Site 10

St Louis, Missouri, 63104, United States

Location

Research Site 12

New York, New York, 10032, United States

Location

Research Site 1

Charleston, South Carolina, 29425, United States

Location

Research Site 4

Nashville, Tennessee, 37232, United States

Location

Research Site 19

Houston, Texas, 77030, United States

Location

Research Site 16

Salt Lake City, Utah, 84132, United States

Location

Research Site 27

Aachen, 52074, Germany

Location

Research Site 22

Pavia, 27100, Italy

Location

Research Site 23

Leiden, 2333 ZA, Netherlands

Location

Research Site 24

Funchal, 9004-514, Portugal

Location

Research Site 20

Barcelona, 08035, Spain

Location

Related Publications (2)

  • 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.

    PMID: 38964420DERIVED

  • 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.

    PMID: 34256305DERIVED

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesSubcutaneous EmphysemaEmphysemaPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Patrick O'Brien, Chief Operating Officer
Organization
Arrowhead Pharmaceuticals, Inc.
PObrien@arrowheadpharma.com
626-304-3400

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 8, 2019

First Posted

May 10, 2019

Study Start

August 7, 2019

Primary Completion

November 8, 2021

Study Completion

September 18, 2023

Last Updated

November 4, 2025

Results First Posted

December 30, 2024

Record last verified: 2025-10

Data Sharing

IPD Sharing
Will not share

Locations

US(16)DE(1)NL(1)IT(1)ES(1)PT(1)