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Purpose

The main aim of this study is to learn if fazirsiran reduces liver scarring (fibrosis) compared to placebo. Other aims are to learn if fazirsiran slows down the disease worsening in the liver, to get information on how fazirsiran affects the body (called pharmacodynamics), to learn if fazirsiran reduces other liver injury (inflammation) and the abnormal Z-AAT protein in the liver, to get information on how the body processes fazirsiran (called pharmacokinetics), to test how well fazirsiran works compared with a placebo in improving measures of liver scarring including imaging and liver biomarkers (substances in the blood that the body normally makes and help show if liver function is improving, staying the same, or getting worse) as well as to check for side effects in participants treated with fazirsiran compared with those who received placebo. Participants will either receive fazirsiran or placebo. Liver biopsies, a way of collecting a small tissue sample from the liver, will be taken twice during this study.

Condition

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 study laboratory manual. - 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 for at least 6 months before 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 bleeding portal hypertensive 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 red 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 cholangitis, 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. - 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Fazirsiran 		Participants will receive fazirsiran 200 milligram per milliliter (mg/ml) subcutaneous (SC) injection on Day 1, at Week 4, and then every 12 weeks (Q12 W) thereafter up to Week 196.
  • Drug: Fazirsiran Injection
    Participants will receive fazirsiran 200 mg/ml SC injection on Day 1, at Week 4, and Q12 W thereafter up to Week 196.
    Other names:
    • TAK-999, ARO-AAT, ADS-001
Placebo Comparator
Placebo 		Participants will receive placebo on Day 1, at Week 4, and Q12 W thereafter up to Week 196.
  • Other: Placebo
    Participants will receive placebo (sterile normal saline [0.9% NaCl]) SC injection on Day 1, at Week 4, and Q12 W thereafter up to Week 196.
    Other names:
    • Sodium chloride

Recruiting Locations

University of Alabama at Birmingham
Birmingham 4049979, Alabama 4829764 35233
Contact:
Site Contact
205-934-9999
grayme@uab.edu

St. Joseph's Hospital and Medical Center
Phoenix 5308655, Arizona 5551752 85013
Contact:
Site Contact
602-406-7791
nilofar.najafian@commonspirit.org

Mayo Clinic
Phoenix 5308655, Arizona 5551752 85054-4502
Contact:
Site Contact
507-284-9523
vargas.hugo@mayo.edu

University of Arizona Thomas D. Boyer Liver Institute
Tucson 5318313, Arizona 5551752 85724-5136
Contact:
Site Contact
520-626-3005
gdblock@deptofmed.arizona.edu

University of California San Diego, Altman Clinical and Translational Institute
La Jolla 5363943, California 5332921 92093
Contact:
Site Contact
858-657-7076
roloomba@health.ucsd.edu

UCLA Pulmonary and Critical Care
Los Angeles 5368361, California 5332921 90095-8344
Contact:
Site Contact
310-825-6170
ibarjaktarevic@mednet.ucla.edu

Stanford University
Palo Alto 5380748, California 5332921 94303
Contact:
Site Contact
650-723-6381
pkwo@stanford.edu

University of California Benioff Children's Hospital
San Francisco 5391959, California 5332921 94143
Contact:
Site Contact
415-353-7052
PROSENTH@ucsf.edu

University of Florida
Gainesville 4156404, Florida 4155751 32611
Contact:
Site Contact
352-294-5152
briana.foerman@medicine.ufl.edu

Schiff Center for Liver Diseases/University of Miami
Miami 4164138, Florida 4155751 33136-1051
Contact:
Site Contact
305-243-1020
eschiff@med.miami.edu

Indiana University School of Medicine - Indianapolis
Indianapolis 4259418, Indiana 4921868 46202
Contact:
Site Contact
317-278-6215
rvuppala@iu.edu; mandcruz@iu.edu

University of Iowa Hospitals and Clinics
Iowa City 4862034, Iowa 4862182 52242
Contact:
Site Contact
319-356-2577
tomohiro-tanaka@uiowa.edu

University of Maryland Medical Center
Baltimore 4347778, Maryland 4361885 21201-1504
Contact:
Site Contact
410-328-1358
kshetty@som.umaryland.edu

Brigham and Womens Hospital
Boston 4930956, Massachusetts 6254926 02115
Contact:
Site Contact
617-525-1267
NHASHEMI@BWH.HARVARD.EDU

Boston Medical Center
Boston 4930956, Massachusetts 6254926 02118-2908
Contact:
Site Contact
617-638-8000
amohanty@bu.edu

University of Michigan Hospital
Ann Arbor 4984247, Michigan 5001836 48109
Contact:
Site Contact
734-232-3741
rfontana@med.umich.edu

Henry Ford Medical Center - Columbus
Novi 5004062, Michigan 5001836 48377-3600
Contact:
Site Contact
248-344-6688
sgordon3@hfhs.org

Mayo Clinic - PPDS
Rochester 5043473, Minnesota 5037779 55905-0001
Contact:
Site Contact
507-284-0686
malhi.harmeet@mayo.edu

Cardinal Glennon Children's Hospital
St Louis 4407066, Missouri 4398678 63104-1003
Contact:
Site Contact
314-577-5633
jeffrey.teckman@slucare.ssmhealth.com

Washington University School of Medicine in St. Louis
St Louis 4407066, Missouri 4398678 63110
Contact:
Site Contact
314-454-8025
smeduchenry@wustl.edu

NYU Langone Health
New York 5128581, New York 5128638 10016
Contact:
Site Contact
212-263-3643
viviana.figueroadiaz@nyulangone.org

Columbia University Irving Medical Center
New York 5128581, New York 5128638 10032-3722
Contact:
Site Contact
212-305-2862
mpg2124@cumc.columbia.edu

University Hospitals Cleveland Medical Center
Cleveland 5150529, Ohio 5165418 44106-1716
Contact:
Site Contact
216-983-0879
seth.sclair@uhhospitals.org

Penn State Health Milton S. Hershey Medical Center
Hershey 5193342, Pennsylvania 6254927 17033
Contact:
Site Contact
717-531-6525
tcraig@pennstatehealth.psu.edu

Temple University Hospital
Philadelphia 4560349, Pennsylvania 6254927 19140-5103
Contact:
Site Contact
215-707-5067
yedidya.saiman@tuhs.temple.edu

Medical University of South Carolina
Charleston 4574324, South Carolina 4597040 29425
Contact:
Site Contact
843-792-5300
strangec@musc.edu

Vanderbilt University Medical Center
Nashville 4644585, Tennessee 4662168 37232-0028
Contact:
Site Contact
615-322-8748
roman.perri@vumc.org

Texoma Liver Center
Denison 4685892, Texas 4736286 75020
Contact:
Site Contact
903-957-0417
h.elgouhari@somacinicaltrials.com

Baylor College of Medicine Medical Center
Houston 4699066, Texas 4736286 77030-4202
Contact:
Site Contact
832-355-1400
george.cholankeril@bcm.edu

The Texas Liver Institute
San Antonio 4726206, Texas 4736286 78215
Contact:
Site Contact
210-253-3426
lawitz@txliver.com

Bon Secours St. Mary's Hospital
Richmond 4781708, Virginia 6254928 23226
Contact:
Site Contact
804-977-8920
mitchell_shiffman@bshsi.org

VCU Medical Center North Hospital
Richmond 4781708, Virginia 6254928 23298-5028
Contact:
Site Contact
212-824-7587
amon.asgharpour@vcuhealth.org

More Details

NCT ID
NCT05677971
Status
Recruiting
Sponsor
Takeda

Study Contact

Takeda Contact
1-877-825-3327
medinfoUS@takeda.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.

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