Hepatic Impairment
Conditions
Brief 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. 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.
Interventions
DRUGFazirsiran
Fazirsiran SC injection
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria for All Participants * 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. * 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.
Exclusion criteria
Key
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Fazirsiran | From pre-dose up to Month 6 post-dose |
| Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Fazirsiran | From pre-dose up to Month 6 post-dose |
| Maximum Observed Plasma Concentration (Cmax) for Fazirsiran | From pre-dose up to Month 6 post-dose |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From the first dose of study drug up to end of follow-up (up to 6 months) |
| Number of Participants With Clinically Significant Abnormal Values for Laboratory Parameters | From the first dose of study drug up to end of follow-up (up to 6 months) |
| Number of Participants With Clinically Significant Abnormal Values for Vital Signs Parameters | From the first dose of study drug up to end of follow-up (up to 6 months) |
| Number of Participants With Clinically Significant Abnormal Values for Electrocardiogram (ECG) Parameters | From the first dose of study drug up to end of follow-up (up to 6 months) |
| Number of Participants With Clinically Significant Abnormal Values for Pulmonary Function Parameters | From the first dose of study drug up to end of follow-up (up to 6 months) |
| Number of Participants With Injection Site Reaction | From the first dose of study drug up to end of follow-up (up to 6 months) |
| Amount of Drug Excreted in Urine From Time 0 to Time 24 hours (Ae0-24hrs) for Fazirsiran | Pre-dose, 0 to 24 hours post-dose |
| Amount of Drug Excreted in Urine From Time 0 to Time 6 hours (Ae0-6hrs) for Fazirsiran | Pre-dose, 0 to 6 hours post-dose |
| Amount of Drug Excreted in Urine From Time 6 to Time 24 hours (Ae6-24h) for Fazirsiran | From 6 to 24 hours post-dose |
| Percent of Recovered Drug in Urine Compared With the Dose (%Dose [u]) | Pre-dose, 0 to 24 hours post-dose |
| Renal Clearance (CLr) for Fazirsiran | Pre-dose, 0 to 24 hours post-dose |
| Absolute Change in Serum Alpha-1 Antitrypsin (AAT) at Nadir | From Day 1 Pre-dose Baseline up to end of follow-up (up to 6 months) |
| Percentage Change in Serum AAT at Nadir | From Day 1 Pre-dose Baseline up to end of follow up (up to 6 months) |
| Absolute Change in Serum AAT | From Day 1 Pre-dose Baseline and at Days 15, 29, 57 |
| Percentage Change in Serum AAT | From Day 1 Pre-dose Baseline and at Days 15, 29, 57 |
Countries
Hungary, Slovakia
Contacts
STUDY_DIRECTORStudy Director
Takeda
Outcome results
None listed