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A Study About Fazirsiran in People With and Without Liver Problems

Primary Purpose

Hepatic Impairment

Status
Not yet recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Fazirsiran
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Impairment

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Key Inclusion Criteria for Participants with Hepatic Impairment and Participants with Normal Hepatic Function 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. Normal lung function. 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 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 arms 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. Exclusion Criteria: Key Exclusion Criteria for Participants with Hepatic Impairment and Participants with Normal Hepatic Function: 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. 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 surgical 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).

Sites / Locations

  • CRU Hungary Kft
  • Summit Clinical Research s.r.o.
  • Summit Clinical Research s.r.o.
  • Summit Clinical Research s.r.o.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm 1, Mild HI: Fazirsiran 200 mg

Arm 2, Moderate HI: Fazirsiran 200 mg

Arm 3, Severe HI: Fazirsiran 200 mg

Arm 4, Normal Hepatic Function: Fazirsiran 200 mg

Arm Description

Participants with mild hepatic impairment (HI) will receive fazirsiran 200 milligrams (mg) subcutaneous (SC) injection on Day 1.

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.

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.

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.

Outcomes

Primary Outcome Measures

Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Fazirsiran
Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Fazirsiran
Maximum Observed Plasma Concentration (Cmax) for Fazirsiran

Secondary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Number of Participants With Clinically Significant Abnormal Values for Laboratory Parameters
Number of Participants With Clinically Significant Abnormal Values for Vital Signs Parameters
Number of Participants With Clinically Significant Abnormal Values for Electrocardiogram (ECG) Parameters
Number of Participants With Clinically Significant Abnormal Values for Pulmonary Function Parameters
Number of Participants With Injection Site Reaction
Amount of Drug Excreted in Urine From Time 0 to Time 24 hours (Ae0-24hrs) for Fazirsiran
Amount of Drug Excreted in Urine From Time 0 to Time 6 hours (Ae0-6hrs) for Fazirsiran
Amount of Drug Excreted in Urine From Time 6 to Time 24 hours (Ae6-24h) for Fazirsiran
Percent of Recovered Drug in Urine Compared With the Dose (%Dose [u])
Renal Clearance (CLr) for Fazirsiran
Absolute Change in Serum Alpha-1 Antitrypsin (AAT) at Nadir
Percentage Change in Serum AAT at Nadir
Absolute Change in Serum AAT
Percentage Change in Serum AAT

Full Information

First Posted
May 26, 2023
Last Updated
July 20, 2023
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT05891158
Brief Title
A Study About Fazirsiran in People With and Without Liver Problems
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 25, 2023 (Anticipated)
Primary Completion Date
February 15, 2025 (Anticipated)
Study Completion Date
February 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1, Mild HI: Fazirsiran 200 mg
Arm Type
Experimental
Arm Description
Participants with mild hepatic impairment (HI) will receive fazirsiran 200 milligrams (mg) subcutaneous (SC) injection on Day 1.
Arm Title
Arm 2, Moderate HI: Fazirsiran 200 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 3, Severe HI: Fazirsiran 200 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 4, Normal Hepatic Function: Fazirsiran 200 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fazirsiran
Other Intervention Name(s)
TAK-999
Intervention Description
Fazirsiran SC injection.
Primary Outcome Measure Information:
Title
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
Title
Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Fazirsiran
Time Frame
From pre-dose up to Month 6 post-dose
Title
Maximum Observed Plasma Concentration (Cmax) for Fazirsiran
Time Frame
From pre-dose up to Month 6 post-dose
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame
From the first dose of study drug up to end of follow-up (up to 6 months)
Title
Number of Participants With Clinically Significant Abnormal Values for Laboratory Parameters
Time Frame
From the first dose of study drug up to end of follow-up (up to 6 months)
Title
Number of Participants With Clinically Significant Abnormal Values for Vital Signs Parameters
Time Frame
From the first dose of study drug up to end of follow-up (up to 6 months)
Title
Number of Participants With Clinically Significant Abnormal Values for Electrocardiogram (ECG) Parameters
Time Frame
From the first dose of study drug up to end of follow-up (up to 6 months)
Title
Number of Participants With Clinically Significant Abnormal Values for Pulmonary Function Parameters
Time Frame
From the first dose of study drug up to end of follow-up (up to 6 months)
Title
Number of Participants With Injection Site Reaction
Time Frame
From the first dose of study drug up to end of follow-up (up to 6 months)
Title
Amount of Drug Excreted in Urine From Time 0 to Time 24 hours (Ae0-24hrs) for Fazirsiran
Time Frame
Pre-dose, 0 to 24 hours post-dose
Title
Amount of Drug Excreted in Urine From Time 0 to Time 6 hours (Ae0-6hrs) for Fazirsiran
Time Frame
Pre-dose, 0 to 6 hours post-dose
Title
Amount of Drug Excreted in Urine From Time 6 to Time 24 hours (Ae6-24h) for Fazirsiran
Time Frame
From 6 to 24 hours post-dose
Title
Percent of Recovered Drug in Urine Compared With the Dose (%Dose [u])
Time Frame
Pre-dose, 0 to 24 hours post-dose
Title
Renal Clearance (CLr) for Fazirsiran
Time Frame
Pre-dose, 0 to 24 hours post-dose
Title
Absolute Change in Serum Alpha-1 Antitrypsin (AAT) at Nadir
Time Frame
From Day 1 Pre-dose Baseline up to end of follow-up (up to 6 months)
Title
Percentage Change in Serum AAT at Nadir
Time Frame
From Day 1 Pre-dose Baseline up to end of follow up (up to 6 months)
Title
Absolute Change in Serum AAT
Time Frame
From Day 1 Pre-dose Baseline and at Days 15, 29, 57
Title
Percentage Change in Serum AAT
Time Frame
From Day 1 Pre-dose Baseline and at Days 15, 29, 57

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Key Inclusion Criteria for Participants with Hepatic Impairment and Participants with Normal Hepatic Function 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. Normal lung function. 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 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 arms 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. Exclusion Criteria: Key Exclusion Criteria for Participants with Hepatic Impairment and Participants with Normal Hepatic Function: 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. 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 surgical 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Takeda Contact
Phone
+1-877-825-3327
Email
medinfoUS@takeda.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
CRU Hungary Kft
City
Kistarcsa
ZIP/Postal Code
2143
Country
Hungary
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Geza Lakner
Facility Name
Summit Clinical Research s.r.o.
City
Bratislava
ZIP/Postal Code
851 05
Country
Slovakia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Email
kupcova@vnet.sk
First Name & Middle Initial & Last Name & Degree
Viera Kupcova
Facility Name
Summit Clinical Research s.r.o.
City
Malacky
Country
Slovakia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
00421 34 282 97 00
First Name & Middle Initial & Last Name & Degree
Edita Kadlubiakova
Facility Name
Summit Clinical Research s.r.o.
City
Nove Zamky
ZIP/Postal Code
940 34
Country
Slovakia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
00421 35 6912111
First Name & Middle Initial & Last Name & Degree
Jozef Glassa

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Access Criteria
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.
IPD Sharing URL
https://vivli.org/ourmember/takeda/

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A Study About Fazirsiran in People With and Without Liver Problems

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