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Alpha1-Antitrypsin DeficiencyPhase 3NCT05899673

An Extension Study to Learn About the Long-Term Safety of Fazirsiran and if Fazirsiran Can Help People With Alpha-1 Antitrypsin Liver Disease

A Phase 3 study testing Fazirsiran Injection in people with Alpha1-Antitrypsin Deficiency, run by Takeda at 10 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The main aim of this study is to learn if fazirsiran is safe during long-term use in people with liver disease caused by the abnormal Z-alpha-1 antitrypsin (Z-AAT) protein. People who have taken part in previous fazirsiran studies (AROAAT2001 [NCT03945292] or AROAAT2002 [NCT03946449]) can continue to receive… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Alpha1-Antitrypsin Deficiency
What is being tested?
Fazirsiran Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
10 sitesin 5 countries
Study dates
8 Aug 2023to 2 May 2033
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must meet all of the following criteria to be eligible for inclusion in the study:
  • The participant is willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
  • The participant is able to read, understand, and complete the study questionnaires electronically per investigator's judgment.
  • The participant has provided informed consent (ICF) (that is, in writing, documented via a signed and dated ICF) and any required privacy authorization before the initiation of any study procedures.
  • Note: For participants who comprehend, can provide informed consent, and are unable to sign the ICF, an impartial witness may sign the ICF on behalf of the participant after the participant has orally consented to the participant's participation in the study.
  • The participant enrolling in this open-label extension (OLE) study will have participated in a previously qualifying study, and will be considered for eligibility based on the following study-specific criteria:
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  • AROAAT2001:
  • Participants with fibrosis may roll over into this OLE study after they reach their next regularly scheduled, Q12W visit.
  • Participants with fibrosis who have completed the AROAAT2001 study may be enrolled into the OLE study.
  • AROAAT2002:
  • Participants in Cohorts 1 and 1b may roll over after completing the 24-week primary study period.
  • Participants in Cohort 2 may roll over after completing the 48-week primary study period.
  • Participants who have completed the study may be enrolled into the OLE study.
  • The participant is a nonsmoker (defined as: does not smoke cigarettes daily for at least 24 weeks) with current nonsmoking status confirmed by urine cotinine at Day 1.
  • E-cigarettes (vapor) are not permitted.
  • The participant may be on nicotine replacement (patch or gum). A positive urine cotinine result due to nicotine replacement is acceptable for enrollment at the discretion of the investigator.
  • The participant must have suitable venous access for blood sampling.
  • It must be confirmed that the participant does not have hepatocellular carcinoma (HCC). Participants will be screened for HCC with alpha-fetoprotein (AFP) and abdominal ultrasound. If the participant has any of the following, they will be required to have contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) imaging to exclude HCC before enrollment.
  • AFP >20 nanogram per milliliter (ng/mL).
  • AFP 15 to 19 ng/mL at enrollment if that is >2 times prestudy levels (if available).
  • Any liver lesion >10 millimeter (mm) (longest diameter) detected by ultrasound.
  • Poor visibility of liver on ultrasound.
  • A person of childbearing potential (POCBP) must have a negative urine pregnancy test performed within 3 days prior to Day 1 dosing in this study (sensitive to 25 International Unit [IU] human chorionic gonadotropin [hCG]).
  • The participant must use appropriate contraception methods (that is, highly effective methods for female and medically appropriate methods for male study participants) for the entire duration of the study. Participants who terminate early must use appropriate contraception methods for 6 months after the last dose of study intervention. Male participants who terminate early must not donate sperm for at least 6 months after the last dose of study intervention.
  • Sexual abstinence, for the purposes of this study, is only considered a highly effective method of contraception when considered to align with the preferred and usual lifestyle of the participant. It will be employed for the entire duration of the study and the 6 months after last dose of study intervention.
  • Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea methods are not considered "true" abstinence and are not acceptable methods of contraception.

Who cannot join

  • The participant will be excluded from the study if any of the following exclusion criteria are met:
  • The participant is likely to require major surgery. Major surgery typically requires at least 1 night in the hospital. Examples include laparoscopic surgery (except cholecystectomy and tubal ligation); Gastrointestinal tract (GI) tract surgery including 1 or more segments of the colon or terminal ileum; open resection of organs; large joint replacements; mastectomy with reconstruction; and spine, thoracic, vascular, or intracranial surgery.
  • The participant has evidence of other forms of chronic liver diseases, including viral hepatitis B or C, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease, alcoholic hepatitis, hemochromatosis, liver cancer, history of biliary diversion, or autoimmune hepatitis.
  • The participant has abnormal finding(s) of clinical relevance during the evaluation before the first study dosing that, in the opinion of the investigator, could adversely impact participant safety during the study or adversely impact study results. For US only: Participants with baseline emphysema may be allowed into the OLE if their lung disease has been stable.
  • The participant had major protocol deviation(s) in AROAAT2001 or AROAAT2002 that would affect the conduct of this study.
  • The participant permanently discontinued investigational product because of an AE, adjudicated as related to the study intervention, in AROAAT2001 or AROAAT2002.
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  • Female participants who became pregnant during Study AROAAT2001 or AROAAT2002, female participants who are lactating or planning to become pregnant during the study period; or males or female participants of childbearing potential not agreeing to continue using appropriate contraception methods through the conclusion of study participation.
  • The participant has a Child-Turcotte-Pugh (CTP) score >=7 OR (Model for End-Stage Liver Disease) MELD score >14.
  • The participant meets Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatinine criteria as per the protocol. All laboratory tests used as exclusion criteria may be repeated once and the repeat value may be used for study eligibility determination.
  • Participants who have a newly-diagnosed malignancy or recurrence of malignancy (except for resected cutaneous basal cell carcinoma, squamous cell carcinoma, superficial bladder tumors, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence).
  • The participant is experiencing a pulmonary exacerbation at the time of enrollment (participant enrollment may be temporarily delayed after the clinical resolution of an exacerbation).
  • The participant has unstable, poorly controlled, or severe hypertension. Participants may be reevaluated once their blood pressure is successfully controlled.
  • The participant has a history of more than moderate alcohol consumption within 12 months before the Day 1 visit.
  • The participant has a history of hypersensitivity or allergies to fazirsiran or any associated excipients.
  • The participant has any concomitant medical or psychiatric condition or social situation that would make it difficult to comply with protocol requirements or put the participant at additional safety risk.
  • The participant has a history of clinically significant hematologic, renal, hepatic, cardiovascular, infectious, pulmonary, neurologic, psychiatric, GI, systemic inflammatory, metabolic, or endocrine disorder or any other condition that, in the opinion of the investigator, rendered the participant a poor candidate for inclusion into the study.
  • The participant has a history of thromboembolic disease (including deep vein thrombosis or pulmonary embolism), within 24 weeks before enrollment; or is taking chronic anticoagulants. (Note: Participants taking stable doses of chronic anticoagulants may be allowed after consultation with the medical monitor, if they do not have cirrhosis or a history of liver decompensating events).
  • The participant is unable to return for all scheduled study visits.
  • The participant has known or suspected coronavirus disease 2019 (COVID-19) that in the opinion of the sponsor and investigator does not resolve during screening. Positive antibody testing for COVID-19 without other evidence of current or recent active infection does not exclude participation. Enrollment of participants who fail inclusion due to COVID-19 infection may be temporarily delayed at the discretion of the sponsor and investigator. If the participant has a positive polymerase chain reaction (PCR) with no other evidence of infection, a retest may be allowed; however, to enroll in the study the participant must have a negative PCR.
  • The participant is a study site employee, an immediate family member (for example, spouse, parent, child, sibling), or is in a dependent relationship with a study site employee who is involved in conduct of this study, or may consent under duress.
  • The participant who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures.
  • The participant who participates in other studies involving an investigational product.

Trial locations and contacts

10 sites in 5 countries.

10 sites in 5 countries

United States5 sites

  • Medical University of South Carolina - Hollings Cancer Center - PPDS

    Charleston, South Carolina, 29425-8900

  • UF Clinical and Translational Science Institute

    Gainesville, Florida, 32610-3010

  • University Of Iowa Hospitals And Clinics

    Iowa City, Iowa, 52242-1009

  • UCSD Altman Clinical and Translational Research Institute

    La Jolla, California, 92037-1337

  • Stanford Medicine Outpatient Center

    Redwood City, California, 94063

Other trials in United States

United Kingdom2 sites

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

  • Royal Infirmary of Edinburgh - PPDS

    Edinburgh, EH16 4SA

Other trials in United Kingdom

Austria1 site

  • Medizinische Universitat Wien (Medical University of Vienna)

    Vienna, A-1090

Other trials in Austria

Germany1 site

  • Universitätsklinikum der RWTH Aachen

    Aachen, North Rhine-Westphalia, 52074

Other trials in Germany

Portugal1 site

  • Hospital Nélio Mendonça

    Funchal, 9000-168

Other trials in Portugal

About this study

Official title: A Phase 3, Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Fazirsiran in Participants With Alpha-1 Antitrypsin Deficiency-Associated Liver Disease

The main aim of this study is to learn if fazirsiran is safe during long-term use in people with liver disease caused by the abnormal Z-alpha-1 antitrypsin (Z-AAT) protein. People who have taken part in previous fazirsiran studies (AROAAT2001 [NCT03945292] or AROAAT2002 [NCT03946449]) can continue to receive fazirsiran every 3 months as long as they participate in this study, the study is ongoing or until health authorities in their country approve fazirsiran to be publicly available. The study may also provide information on whether fazirsiran has a long-term effect in reducing liver fibrosis or slowing down the progression of liver fibrosis in people with liver disease due to the abnormal Z-AAT protein.

Being tested
Fazirsiran Injection
Medical subject headings
alpha 1-Antitrypsin Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fazirsiran InjectionDrug

    Also called TAK-999, ARO-AAT

    Fazirsiran will be injected subcutaneously.

Study groups in NCT05899673
Study groupRoleWhat they receive
Fazirsiran 200 mgExperimentalParticipants who are currently taking part in or who have completed their treatment in parent studies AROAAT2001 (NCT03945292) and AROAAT2002 (NCT03946449) may rollover in this study to receive fazirsiran, 200 milligrams (mg), injection, subcutaneously on Day 1 and once every 12 weeks (Q12W) thereafter until fazirsiran receives approval and is commercially available in the participant's country, until a participant withdraws from the study or the sponsor decides to terminate the study.
Receives: Drug: Fazirsiran Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the study intervention, whether or not it is considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study intervention. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, suspected transmission of any infectious agent, an important medical event. AEs and SAEs including any pulmonary AEs or SAEs indicative of worsening pulmonary condition (example, pulmonary exacerbation, respiratory infection, significant pulmonary function test decline) will be reported.

    Measured: From start of study drug administration (in current study) up to End of study (EOS) (current study [up to 10 years])

  2. Number of Participants With Clinically Significant Changes From Baseline in Pulmonary Function Parameters

    Standard pulmonary function parameters measured will be used to study lung function. Clinical significance of pulmonary function parameters will be determined at the investigator's discretion.

    Measured: Baseline (current study), up to EOS (current study up to 10 years])

  3. Number of Participants With Clinically Significant Changes in Vital Signs

    Vital signs include body temperature, respiratory rate, sitting blood pressure (systolic and diastolic, resting more than 5 minutes), pulse, oxygen saturation. Clinical significance of vital signs will be determined at the investigator's discretion.

    Measured: From start of study drug administration (in current study) up to EOS (current study [up to 10 years])

  4. Number of Participants With Clinically Significant Changes in Laboratory Parameters

    Laboratory parameters include hematology, biochemistry including liver tests, coagulation, and urinalysis. Clinical significance of laboratory parameters will be determined at the investigator's discretion.

    Measured: From start of study drug administration (in current study) up to EOS (current study [up to 10 years])

Secondary outcomes (6)

  1. Number of Participants With no Progression from Baseline of At least 1 Stage of Histologic Fibrosis on Liver Biopsy at Week 102

    Number of participants with no progression from baseline of at least 1 stage of histologic fibrosis (by Meta-Analysis of Histological Data in Viral Hepatitis [METAVIR] staging) on liver biopsy at Week 102 will be reported.

    Measured: At Week 102 (current study)

  2. Number of Participants With Reduction from Baseline of At least 1 Stage of Histologic Fibrosis on Liver Biopsy at Week 102

    Number of participants with baseline fibrosis of F1 or higher, a decrease from baseline of at least 1 stage of histologic fibrosis (by METAVIR staging) on liver biopsy at Week 102 will be reported.

    Measured: At Week 102 (current study)

  3. Change from Baseline in Intrahepatic Z-AAT Protein Polymer Burden Assessed by Periodic Acid Schiff Plus Diastase (PAS+D) Staining in Liver Biopsy at Week 102

    Change from baseline in intrahepatic Z-AAT protein polymer burden assessed by PAS+D staining in liver biopsy will be assessed.

    Measured: Baseline (current study), Week 102 (current study)

  4. Change from Baseline in Intrahepatic Portal Inflammation Score at Week 102 in Liver Biopsy

    Change in portal inflammation score in liver biopsy, based on pathology slide reads. Inflammation will be assessed on a scale of 0-3, with higher scores showing more severe inflammation.

    Measured: Baseline (current study), Week 102 (current study)

  5. Change from Baseline in Liver Stiffness Assessed by Magnetic Resonance Elastography (MRE)

    Change from baseline in MRE-derived liver stiffness will be assessed.

    Measured: Baseline (current study), up to EOS (current study up to 10 years])

  6. Change from Baseline in Liver Stiffness Assessed by Vibration-Controlled Transient Elastography (VCTE)

    Change from baseline in VCTE-derived liver stiffness will be assessed.

    Measured: Baseline (current study), up to EOS (current study up to 10 years])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2023
  2. Study start8 Aug 2023
  3. Primary completion2 May 2033 (estimated)
  4. Study completion2 May 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05899673
Sponsor's protocol ID
TAK-999-3003
Other IDs
2023-503497-21-00, 2023
Status last verified
Oct 2025
First submitted
2 Jun 2023
Last updated
14 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fazirsiran Injection in people with Alpha1-Antitrypsin Deficiency, run by Takeda at 10 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, United Kingdom, Austria, Germany, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) (time frame: From start of study drug administration (in current study) up to End of study (EOS) (current study [up to 10 years])). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05899673.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2025.

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