Recruiting at 40 sites Phase 3 Alpha1-Antitrypsin Deficiency

Alpha1-Antitrypsin Deficiency study: Fazirsiran Injection

Official title 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 ID: NCT06165341

What this study is testing

What is Fazirsiran Injection?

an investigational subcutaneous injectable medicine being studied as a potential treatment for Alpha‑1 Antitrypsin Deficiency‑related liver disease is designed to reduce the production of the abnormal Z‑AAT protein in the liver

Also referred to as TAK-999, ARO-AAT, ADS-001.

Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing
This study is testing whether fazirsiran is safe and well tolerated and if it reduces liver scarring in people with alpha‑1 antitrypsin deficiency.
Who it's for
You may be able to join if you have alpha‑1 antitrypsin deficiency and mild liver scarring.
What's involved
You will receive either fazirsiran, a medicine that lowers the bad protein, or a pretend treatment with no medicine. You will have two small liver tissue checks during the study.
Time commitment
The study lasts about two years with regular visits and two liver biopsies.
  • Phase 3: a large, late-stage study
  • Time commitment: about 2 years
  • You might receive a placebo (an inactive treatment) instead of the study drug.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 to 75

You may be able to join if

  • In the opinion of the investigator, the participant is capable of understanding and fully complying with the protocol requirements and adhering to...
  • 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).
  • 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.

You likely can't join 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.
See the full eligibility criteria
Who can join
  • 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.
  • 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
  • The participant has a pulmonary status that meets the protocol requirements.
  • It must be confirmed that the participant does not have hepatocellular carcinoma (HCC).
  • Any participant who is taking statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or beta-1 selective adrenergic receptor inhibitors must have been receiving a stable dose of these...
  • An adult participant must have a body mass index (BMI) greater than or equal to (\>=) 18 kilogram per meter square (kg/m\^2).
  • The participant has a 12-lead electrocardiogram at screening that, in the opinion of the investigator, has no abnormalities that could compromise the participant's safety in this study.
  • The participant is a nonsmoker.
  • If the participant was being treated with any respiratory medications including inhaled bronchodilators, inhaled anticholinergics, inhaled corticosteroids, or low-dose systemic corticosteroids (prednisone less than or...
  • The participant must have suitable venous access for blood sampling.
  • A person of childbearing potential (POCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 before dosing.
  • The participant must use appropriate contraception methods (that is, highly effective methods for female and medically appropriate methods for male study participants) for the entire duration of the study and for 6...
What rules you out
  • 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.
  • 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...
  • The participant has any laboratory abnormalities at screening and before the first dose of the study drug that meet protocol parameters.
  • 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 recent lower respiratory tract infection, such as pneumonia, within the last 6 months prior to screening, unless, in the opinion of the investigator, the participant has achieved clinical recovery...
  • The participant has a history of frequent pulmonary exacerbations (\>=2 moderate or severe exacerbations within 52 weeks before screening).
  • The participant is experiencing a pulmonary exacerbation at the time of screening (participant may be rescreened after the clinical resolution of an exacerbation).
  • The participant is receiving long-term, around-the-clock oxygen supplementation or supplemental oxygen with continuous positive airway pressure (CPAP) or bilevel positive airway pressure for acute respiratory failure.
  • The participant has human immunodeficiency virus (HIV) infection as shown by the presence of anti-HIV antibody (seropositive).
  • The participant is seropositive for hepatitis B virus (HBV surface antigen positive and/or HBV core antibody positive without HBV surface antibody at screening) or hepatitis C virus (HCV) (detectable HCV Ribonucleic...
  • The participant has unstable, poorly controlled, or severe hypertension. Participants may be rescreened once their blood pressure (BP) is successfully controlled.
  • The participant has a history of ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the participant if they participate in the study, in the opinion of the investigator.
  • The participant has symptomatic heart failure (per New York Heart Association guidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction less than [\<] 20 percent [%])...
  • The participant has a history of major surgery within 12 weeks of screening (or longer, at the discretion of the investigator).
  • The participant has a history of more than moderate alcohol consumption within 12 months before the screening visit.
  • 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 RNA interference (RNAi) for alpha-1 antitrypsin deficiency-associated liver disease (AATD-LD).
  • The participant has a history of hypersensitivity or allergies with any associated excipients of fazirsiran.
  • The participant has received an investigational agent or device within 30 days, or 5 half-lives, whichever is longer, before the dosing of study medication or is currently participating in an investigational study...
  • The participant has donated \>=500 milliliter (mL) of blood within 1 month of the administration of study treatment.
  • The participant has any concomitant medical or psychiatric condition or social situation that would make it difficult to comply with protocol requirements or put the participant at additional safety risk.
  • The participant has a history of thromboembolic disease (including deep vein thrombosis or pulmonary embolism), within 6 months before screening, or is taking chronic anticoagulants.
  • This participant is unable to return for all scheduled study visits.
  • The participant has symptomatic confirmed coronavirus disease 2019 (COVID-19) that, in the opinion of the investigator, does not resolve during screening
  • The participant is a study site employee involved in the conduct of this study, an immediate family member (example, spouse, parent, child, sibling), is in a dependent relationship with study site employee who is...
  • The participant takes or is required to take excluded medications.
  • The participant is pregnant or breastfeeding or intending to become pregnant before participating in this study, during the study, or within 6 months after last dose of the study drug

The study team makes the final eligibility decision.

Where it is enrolling

  • Phoenix, Arizona, United States
  • Tucson, Arizona, United States
  • La Jolla, California, United States
  • Los Angeles, California, United States
  • San Francisco, California, United States
  • Colorado Springs, Colorado, United States
  • Miami, Florida, United States
  • Indianapolis, Indiana, United States
  • Iowa City, Iowa, United States
  • Boston, Massachusetts, United States
  • Ann Arbor, Michigan, United States
  • Novi, Michigan, United States
  • Rochester, Minnesota, United States
  • New York, New York, United States
  • Cleveland, Ohio, United States
  • Hershey, Pennsylvania, United States
  • San Antonio, Texas, United States
  • Newport, Virginia, United States
  • Graz, Austria
  • Klagenfurt, Austria

+ 18 more site(s).

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.

How long does this study last?

The study runs about 2 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years to 75 years. The study team makes the final eligibility decision.

Where is this trial taking place?

This study is enrolling now at Phoenix, Arizona, United States; Tucson, Arizona, United States; La Jolla, California, United States; Los Angeles, California, United States; San Francisco, California, United States; Colorado Springs, Colorado, United States and 32 more locations. Enter your location above to see the nearest enrolling site and check your eligibility.

Explore other conditions

ObesityType 2 diabetesType 1 diabetesPrediabetesWeight lossMetabolic syndromeHigh cholesterolHigh triglyceridesHigh blood pressurePCOSHypothyroidismThyroid diseaseGoutFatty liver disease (NAFLD/NASH)Heart failureCoronary artery disease

BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.