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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-503735-17-00 | EU Trial (CTIS) Number | EU CTIS |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1, Mild HI: Fazirsiran 200 mg | Experimental | Participants with mild hepatic impairment (HI) will receive fazirsiran 200 milligrams (mg) subcutaneous (SC) injection on Day 1. |
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| Arm 2, Moderate HI: Fazirsiran 200 mg | Experimental | Participants 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. |
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| Arm 3, Severe HI: Fazirsiran 200 mg | Experimental | Participants 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. |
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| Arm 4, Normal Hepatic Function: Fazirsiran 200 mg | Experimental | Participants 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fazirsiran | Drug | Fazirsiran SC injection |
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| Measure | Description | 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 |
| Measure | Description | 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) |
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Inclusion Criteria:
Key Inclusion Criteria for All Participants
Key Inclusion Criteria for Participants with Hepatic Impairment:
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
Exclusion Criteria:
Key Exclusion Criteria for All Participants:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRU Hungary Kft | Kistarcsa | 2143 | Hungary | |||
| Summit Clinical Research s.r.o. |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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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.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
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| 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 |
| Bratislava |
| 851 05 |
| Slovakia |
| Summit Clinical Research s.r.o. | Malacky | Slovakia |
| Summit Clinical Research s.r.o. | Nové Zámky | 940 34 | Slovakia |