Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion criteria:
- The participant must have a diagnosis of the Z allele homozygotes (PiZZ) genotype
AATD. PiZZ diagnosis 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, of any sex, is aged 18 to 75 years, inclusive.
- The participant's liver biopsy core sample collected should meet the requirements of
the protocol.
- The participant has evidence of METAVIR stage F2, F3, or F4 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 of a previous biopsy conducted
within 6 months before the estimated enrollment date using an adequate liver biopsy
and slides as defined in the histopathology manual. The histopathology manual must be
followed for all liver biopsies as study standard operating procedure.
- The participant has a pulmonary status meeting the protocol's requirements.
- It must be confirmed that the participant does not have HCC. Participants will be
screened for HCC with alpha-fetoprotein (AFP) and abdominal ultrasound. If the
participant has any of the following, they will be required to have contrast-enhanced
CT or MRI imaging to exclude HCC before randomization.
- An adult participant must have a body mass index (BMI) between 18.0 and 39.0 kilograms
per meter square (kg^m2), inclusive.
- The participant is a nonsmoker (defined as does not smoke cigarettes daily for at
least 12 months before screening) with current nonsmoking status confirmed by urine
cotinine at screening.
Exclusion Criteria
- The participant has a history of liver decompensating events (overt hepatic
encephalopathy [West Haven Grade >=2] documented by a physician, clinically
significant ascites, spontaneous bacterial peritonitis, GI bleeding from varices,
hepatopulmonary syndrome, hepatorenal syndrome, portal pulmonary hypertension, or
portal gastropathy).
- The participant has a history of the presence of medium or large varices or varices
with red wale signs based on a previous esophagogastroduodenoscopy (EGD) within 6
months before the estimated enrollment date. For certain participants, an EGD will be
required at screening if there is no EGD available within 6 months before the
estimated enrollment date. Presence of small varices with no wale signs on EGD and no
history of bleeding will be acceptable for study eligibility.
- The participant has evidence of other forms of chronic liver diseases, including viral
hepatitis B or C, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson
disease, alcoholic hepatitis, hemochromatosis, liver cancer, history of biliary
diversion, or autoimmune hepatitis.
- The participant has alanine transaminase (ALT) or aspartate transaminase (AST) levels
> 250 units per liter (U/L).
- The participant has a platelet count < 60,000 per cubic millimeter (mm^3) (< 60 × 10^9
per liter [10^9/L]).
- The participant has albumin ≤ 2.8 gram per deciliter (g/dL) (28 grams per deciliter
[g/L]).
- The participant has international normalized ratio (INR) ≥ 1.7.
- The participant is expected to have severe and unavoidable high-level exposure to
inhaled pulmonary toxins during the study such as may occur with occupational exposure
to mineral dusts or metals.
- The participant has a history of drug abuse (such as cocaine, phencyclidine) within 1
year before the screening visit or has a positive urine drug screen at screening. A
urine drug screen positive for benzodiazepines, opioids, or tetrahydrocannabinol is
acceptable for enrollment at the discretion of the investigator if the positive test
is due to a substance used for medical reasons.
- The participant has previously been treated with fazirsiran or any other RNAi for
AATD-LD.
- The participant has portal vein thrombosis.
- The participant has a prior transjugular portosystemic shunt procedure.
- 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 other curatively treated
malignancies who have no evidence of metastatic disease and a greater than 1-year
disease-free interval may be entered after approval by the medical monitor.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 3/15/23. Questions regarding updates should be directed to the study team contact.