RecruitingAlpha1-Antitrypsin Deficiency

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)

Eligible age

18–75 yrs

Accepts

All genders

Locations

14 states

Healthy volunteers

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About this study

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 end stage 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.

Sponsor: Takeda

You may qualify if…

✓ In the opinion of the investigator, the participant is capable of understanding and fully complying with the protocol requirements and adhering to the protocol schedule.
✓ The participant is able to read, understand, and complete the study questionnaires electronically per the investigator's judgment.
✓ The participant signs and dates a written Informed Consent Form (ICF). Any required privacy authorization should also be signed before the initiation of any study procedures.
✓ The participant, of any sex, is aged 18 to 75 years, inclusive.
✓ The participant must have a diagnosis of the protease inhibitor Z mutation (PiZZ) genotype AATD. A diagnosis of PiZZ from source-verifiable medical records is permitted. Otherwise, participants must undergo PiZZ confirmatory testing (genotyping for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are not permitted.
✓ The participant's liver biopsy core samples collected as per protocol requirements.
✓ The participant has evidence of METAVIR stage F1 liver fibrosis, evaluated by a centrally read baseline liver biopsy during the screening period; or confirmed as meeting all the entry criteria by central reading from a previous biopsy conducted within 1 year before the estimated enrollment date using an adequate liver biopsy and slides as defined in the study laboratory manual.
✓ The participant has a pulmonary status that meets the protocol requirements.

You may not qualify if…

✕ The participant has evidence of \>= F2 fibrosis based on liver biopsy during the screening period.
✕ The participant has a history of liver decompensating events.
✕ The participant has a history of varices based on a previous esophagogastroduodenoscopy.
✕ The participant has portal vein thrombosis.
✕ The participant has undergone a prior trans-jugular portosystemic shunt procedure.
✕ The participant has evidence of other forms of chronic liver diseases.
✕ The participant has a history of malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Participants with curatively treated malignancies who have no evidence of metastatic disease and disease-free interval greater than (\>) 1 year may be enrolled after approval by the medical monitor.
✕ The participant has an abnormal finding of clinical relevance at the screening evaluation and before administration of the first dose of study dosing that, in the opinion of the investigator, could adversely impact participant safety during the study or adversely impact study results.