TAK-999-3002

Recruiting

Study to Learn About the Safety of Fazirsiran and if it Can Help People With Alpha-1 Antitrypsin Liver Disease With Mild Liver Scarring (Fibrosis)

Clinicaltrials.gov

|

EU CTIS

#2023-504198-19-00

The liver produces a protein called alpha-1 antitrypsin (AAT). AAT is normally released into the bloodstream. In some people, the liver makes an abnormal version of the AAT protein, called Z-AAT. Making an abnormal version of the AAT protein can result in liver disease as Z-AAT builds up in liver cells, which leads to liver problems such as liver scarring (fibrosis), continuing liver damage (cirrhosis), and eventually endstage liver disease. Fazirsiran is a medicine that reduces the creation of the Z-AAT protein and thus the build-up of this abnormal protein in the liver. People with this type of liver disease who already have mild liver scarring will take part in the study. They will be treated with fazirsiran or a placebo for about 2 years. This study will check the long-term safety of fazirsiran, whether participants tolerate the treatment and if there are any effects on liver scarring. A liver biopsy, a way of collecting a small tissue sample from the liver, will be taken twice during the study.

US

PT

DE

9+

Interventional Phase 3 clinical trial.

What medical conditions are being studied?

Alpha1-Antitrypsin Deficiency

What is the clinical trial testing?

Placebo, Fazirsiran Injection

How many participants are being enrolled?

50

Are placebos part of the clinical trial?

Yes

When is the clinical trial being conducted?

Mar 2024 - Aug 2028

How long is participation in the clinical trial?

Participants will stay in the study for up to 2.5 years (132 weeks) and will receive the assigned study treatment for approximately 2 years (100 weeks).

Sexes

All

Age

18 to 75 Years

Healthy volunteers?

No

Men and women from 18 to 75 years old can take part in this study.

Must have the specific gene for abnormal Z-AAT protein (confirmed by a genetic test), and already have Stage F1 liver scarring (fibrosis) shown in the liver biopsy.

Must have acceptable lung function.

Cannot have liver scarring at stage F2, F3, or F4 as shown in the liver biopsy.

Cannot have had symptoms or signs of liver failure or other types of chronic liver disease.

Cannot have had recent, ongoing, or frequent lung infections, or breathing difficulties, or need long term treatment with oxygen.

Cannot be exposed to chemicals, mineral dust, or metals that are toxic to the lungs.

Cannot be smokers.

Additional entry criteria will be discussed with the study doctor.

Primary outcome measures

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [Time Frame: From start of study drug administration up to End of study (EOS) (Week 124)]

Number of Participants With Clinically Significant Change From Baseline in Pulmonary Function Parameters [Time Frame: From start of study drug administration up to EOS (Week 124)]

Change From Baseline in Whole Lung 15th Percentile Density as Measured by Computed Tomography (CT) Lung Densitometry [Time Frame: Baseline up to Week 100]

Number of Participants With Clinically Significant Changes in Vital Signs [Time Frame: From start of study drug administration up to EOS (Week 124)]

Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters [Time Frame: From start of study drug administration up to EOS (Week 124)]

Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters [Time Frame: From start of study drug administration up to EOS (Week 124)]

Secondary outcome measures

Change From Baseline in Serum Z-AAT Protein Over Time to Week 106 [Time Frame: Baseline up to Week 106]

Percent Change From Baseline in Intrahepatic Liver Z-AAT Protein at Week 106 [Time Frame: Baseline up to Week 106]

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 106 [Time Frame: Baseline up to Week 106]

Number of Participants with No Change or Decrease From Baseline in Intrahepatic Z-AAT Protein Polymer Burden Assessed by PAS+D staining at Week 106 [Time Frame: Baseline up to Week 106]

Change From Baseline in Intrahepatic Portal Inflammation Score in Liver Biopsy at Week 106 [Time Frame: Baseline up to Week 106]

Number of Participants with No Change or Decrease From Baseline in Intrahepatic Portal Inflammation Score at Week 106 [Time Frame: Baseline up to Week 106]

Number of Participants With No Change or Decrease From Baseline in Histologic Fibrosis Score (Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] Staging ) at Week 106 [Time Frame: Baseline up to Week 106]

Change From Baseline in Vibration-Controlled Transient Elastography (VCTE)-Derived Liver Stiffness [Time Frame: Baseline up to Week 106]

Change From Baseline in Markers of Liver Injury [Time Frame: Baseline up to Week 106]