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Hepatic ImpairmentPhase 1NCT05891158

A Study About Fazirsiran in People With and Without Liver Problems

A Phase 1 study testing Fazirsiran in people with Hepatic Impairment, run by Takeda at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The main aim of this study is to learn how the body processes fazirsiran (pharmacokinetics [PK]) in people with mild, moderate, or severe liver problems, compared to people with normal liver function. Read more about this study

Who is it for?
Ages 18 to 85 yearsHealthy volunteers can take part
Conditions the study is for
Hepatic Impairment
What is being tested?
Fazirsiran
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
4 sitesin 2 countries
Study dates
5 Oct 2023to 3 Sep 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 to 85 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • A 12-lead ECG at screening that, in the opinion of the investigator, has no abnormalities that compromise the participant's safety in this study.
  • No abnormal finding of clinical relevance at screening or before dosing that in the opinion of the investigator could adversely impact participant safety during the study or adversely impact study results.
  • Key Inclusion Criteria for Participants with Hepatic Impairment:
  • The participant is 18 to 75 years of age inclusive at the time of signing the informed consent form (ICF).
  • The participant has a body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 40.0 kilograms per square meter (kg/m^2) at screening.
  • Aside from HI, the participant must be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, electrocardiograms (ECGs), and screening clinical laboratory profiles, as deemed by the investigator or designee.
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  • Diagnosis of chronic (example, imaging, biopsy, etc.) stable hepatic insufficiency for at least 3 months before screening with features of cirrhosis due to any etiology according to medical history. HI must be stable, that is, no significant changes in hepatic function or clinical status in the 30 days preceding screening (or since the last visit if within 3 months before screening) and with treatment with stable doses of medication.
  • Has a Child-Turcotte-Pugh (CTP) score confirmed by 2 tests as follows:
  • Arm 1: Mild HI, CTP Class A: >=5 and <=6
  • Arm 2: Moderate HI, CTP Class B: >=7 and <=9
  • Arm 3: Severe HI, CTP Class C: >=10 and <=15
  • It must be confirmed that the participant does not have hepatocellular carcinoma (HCC).
  • Key Inclusion Criterion for Participants with Mild Hepatic Impairment • The participant has pulmonary status meeting criteria of percent predicted forced expiratory volume in the first second of expiration (ppFEV1) >=80 percent and percent predicted diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (ppDLCOhgb) >=75%, based on pulmonary function test (PFT) at screening conducted as per American Thoracic Society (ATS)-European Respiratory Society (ERS) criteria.
  • Key Inclusion Criterion for Participants with Moderate and Severe Hepatic Impairment
  • The participant has pulmonary status meeting the criteria defined in the protocol based on PFT at screening conducted as per ATS-ERS criteria.
  • Key Inclusion Criteria for Participants with Normal Hepatic Function
  • The participant is 18 to 85 years of age inclusive, at the time of signing the ICF.
  • The participant has a BMI >=18.0 and <=40.0 kg/m^2, at screening. Participants will be matched to participants with HI by BMI (±15%).
  • AAT level at or above the lower end of the reference range (above or equal to 16.6 micromole (mcM) or 90 milligram per deciliter [mg/dL]) at screening.
  • The participant has normal liver tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBILI) <=1.2 x upper limit of the normal range (ULN) at screening and check-in.
  • The participant has pulmonary status meeting criteria of ppFEV1 >=80%, and ppDLCOhgb >=75%, based on PFT at screening conducted as per ATS- ERS criteria.

Who cannot join

  • The participant has uncontrolled hypertension (systolic blood pressure [BP] >170 mm Hg and diastolic BP >100 millimeter of mercury [mmHg] at screening). Participants may be rescreened once BP is successfully controlled.
  • The participant has a history of torsades de pointes, ventricular rhythm disturbances (example, ventricular tachycardia or fibrillation), heart block (excluding first-degree block, being pulse rate [PR] interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG. Participants with a history of atrial arrhythmias should be discussed with the medical monitor.
  • The participant has symptomatic heart failure (per New York Heart Association guidelines) or severe heart failure with reduced ejection fraction (EF <20%), unstable angina, myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months before screening.
  • The participant is expected to have severe and unavoidable high-level exposure to inhaled pulmonary toxins during the study.
  • The participant has had a recent lower respiratory tract infection, such as pneumonia, within the last 6 months before screening.
  • The participant has a history of malignancy within the last 1 year, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Participants with other curatively treated malignancies who have no evidence of metastatic disease and have been disease-free for >1 year may enter the study after approval by the medical monitor.
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  • The participant has a history of thromboembolic disease (including deep vein thrombosis or pulmonary embolism) within 6 months of screening.
  • Key Exclusion Criteria for Participants with Hepatic Impairment:
  • The participant has a history of gastric or esophageal variceal bleeding within the past 6 months of dosing and for which varices have not been adequately treated with medication and/or endoscopic procedures.
  • The participant has grade >2 hepatic encephalopathy assessed using the West Haven criteria.
  • The participant has evidence of hepatopulmonary syndrome or portal-pulmonary hypertension.
  • The participant has portal vein thrombosis, transjugular intrahepatic portosystemic shunt (TIPS), or surgical portosystemic shunt.
  • The participant has required endoscopic treatment of esophageal or gastric varices or paracentesis to control ascites within the last 3 months of dosing.
  • The participant has chronic hepatitis B (hepatitis B surface antigen positive, or positive for both hepatitis B surface antibody and hepatitis B core antibody but negative for hepatitis B surface antigen); or has chronic or incompletely or unsuccessfully treated hepatitis C (as demonstrated by a positive hepatitis C antibody and positive polymerase chain reaction [PCR]).
  • The participant has any of the following clinically significant abnormal parameters at screening:
  • ALT or AST levels >250 units per liter (U/L) at screening.
  • Estimated glomerular filtration rate <45 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2).

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Slovakia3 sites

  • Summit Clinical Research s.r.o.

    Bratislava, 851 05

  • Summit Clinical Research s.r.o.

    Malacky

  • Summit Clinical Research s.r.o.

    Nové Zámky, 940 34

Other trials in Slovakia

Hungary1 site

  • CRU Hungary Kft

    Kistarcsa, 2143

Other trials in Hungary

About this study

Official title: An Open-Label, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Pharmacodynamics in Response to a Single Subcutaneous Dose of Fazirsiran (TAK-999) in Subjects With or Without Hepatic Impairment

The main aim of this study is to learn how the body processes fazirsiran (pharmacokinetics [PK]) in people with mild, moderate, or severe liver problems, compared to people with normal liver function.

The study will include participants with liver scarring (cirrhosis) and mild, moderate, or severe liver problems, and participants with normal liver function. All participants will be given 1 injection of fazirsiran and will be followed up for 6 months after the fazirsiran injection.

Being tested
Fazirsiran

What participants receive

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

  • FazirsiranDrug

    Also called TAK-999

    Fazirsiran SC injection

Study groups in NCT05891158
Study groupRoleWhat they receive
Arm 1, Mild HI: Fazirsiran 200 mgExperimentalParticipants with mild hepatic impairment (HI) will receive fazirsiran 200 milligrams (mg) subcutaneous (SC) injection on Day 1.
Receives: Drug: Fazirsiran
Arm 2, Moderate HI: Fazirsiran 200 mgExperimentalParticipants with moderate HI will receive fazirsiran 200 mg SC injection on Day 1. The dose may be modified after review of available safety and PK data by the sponsor study team in consultation with the investigator.
Receives: Drug: Fazirsiran
Arm 3, Severe HI: Fazirsiran 200 mgExperimentalParticipants with severe HI will receive fazirsiran 200 mg SC injection on Day 1. The dose may be modified after review of available safety and PK data by the sponsor study team in consultation with the investigator.
Receives: Drug: Fazirsiran
Arm 4, Normal Hepatic Function: Fazirsiran 200 mgExperimentalParticipants with normal hepatic function will receive fazirsiran 200 mg SC injection on Day 1. The dose may be modified after review of available safety and PK data by the sponsor study team in consultation with the investigator.
Receives: Drug: Fazirsiran

What is being measured

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

  1. Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Fazirsiran

    Measured: From pre-dose up to Month 6 post-dose

  2. Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Fazirsiran

    Measured: From pre-dose up to Month 6 post-dose

  3. Maximum Observed Plasma Concentration (Cmax) for Fazirsiran

    Measured: From pre-dose up to Month 6 post-dose

Secondary outcomes (15)

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Measured: From the first dose of study drug up to end of follow-up (up to 6 months)

  2. Number of Participants With Clinically Significant Abnormal Values for Laboratory Parameters

    Measured: From the first dose of study drug up to end of follow-up (up to 6 months)

  3. Number of Participants With Clinically Significant Abnormal Values for Vital Signs Parameters

    Measured: From the first dose of study drug up to end of follow-up (up to 6 months)

  4. Number of Participants With Clinically Significant Abnormal Values for Electrocardiogram (ECG) Parameters

    Measured: From the first dose of study drug up to end of follow-up (up to 6 months)

  5. Number of Participants With Clinically Significant Abnormal Values for Pulmonary Function Parameters

    Measured: From the first dose of study drug up to end of follow-up (up to 6 months)

  6. Number of Participants With Injection Site Reaction

    Measured: From the first dose of study drug up to end of follow-up (up to 6 months)

  7. Amount of Drug Excreted in Urine From Time 0 to Time 24 hours (Ae0-24hrs) for Fazirsiran

    Measured: Pre-dose, 0 to 24 hours post-dose

  8. Amount of Drug Excreted in Urine From Time 0 to Time 6 hours (Ae0-6hrs) for Fazirsiran

    Measured: Pre-dose, 0 to 6 hours post-dose

  9. Amount of Drug Excreted in Urine From Time 6 to Time 24 hours (Ae6-24h) for Fazirsiran

    Measured: From 6 to 24 hours post-dose

  10. Percent of Recovered Drug in Urine Compared With the Dose (%Dose [u])

    Measured: Pre-dose, 0 to 24 hours post-dose

  11. Renal Clearance (CLr) for Fazirsiran

    Measured: Pre-dose, 0 to 24 hours post-dose

  12. Absolute Change in Serum Alpha-1 Antitrypsin (AAT) at Nadir

    Measured: From Day 1 Pre-dose Baseline up to end of follow-up (up to 6 months)

  13. Percentage Change in Serum AAT at Nadir

    Measured: From Day 1 Pre-dose Baseline up to end of follow up (up to 6 months)

  14. Absolute Change in Serum AAT

    Measured: From Day 1 Pre-dose Baseline and at Days 15, 29, 57

  15. Percentage Change in Serum AAT

    Measured: From Day 1 Pre-dose Baseline and at Days 15, 29, 57

Timeline

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

  1. First posted6 Jun 2023
  2. Study start5 Oct 2023
  3. Primary completion3 Sep 2025
  4. Study completion3 Sep 2025

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05891158
Sponsor's protocol ID
TAK-999-1001
Other IDs
2023-503735-17-00, 2023
Status last verified
Mar 2026
First submitted
26 May 2023
Last updated
19 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
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 1 study testing Fazirsiran in people with Hepatic Impairment, run by Takeda at 4 sites in 2 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 21 inclusion and 17 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: finished, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Slovakia, Hungary. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Fazirsiran (time frame: From pre-dose up to Month 6 post-dose). The study lists 3 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 NCT05891158.

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 19 Mar 2026.

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