RecruitingPHASE3INTERVENTIONAL

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)

This research study is investigating a new medication called fazirsiran for people living with Alpha-1 Antitrypsin Deficiency (AATD), a genetic condition. In AATD, the liver makes an abnormal protein (Z-AAT) that builds up and can cause liver damage, leading to scarring, cirrhosis, and eventually serious liver disease. Fazirsiran aims to reduce the production of this problematic protein. The study focuses on participants who already have a mild form of liver scarring. Over approximately two years, participants will receive either fazirsiran or a dummy treatment (placebo). Researchers will monitor the medicine's safety, how well people tolerate it, and its effects on liver scarring by taking small liver tissue samples twice during the study. It's a 'Phase 3' study, meaning it's a later stage of research.

At a glance

Status

Recruiting

Phase

PHASE3

Sponsor

Takeda

Enrolment target

Start

01 Mar 2024

Estimated completion

26 Aug 2028

Alpha1-Antitrypsin Deficiency

What is this study about?

This study is about a genetic liver condition called Alpha-1 Antitrypsin Deficiency (AATD). Normally, a protein called alpha-1 antitrypsin (AAT) is made in the liver and travels through your bloodstream, playing an important role in protecting your body. However, in some people with AATD, the liver produces a faulty version of this protein, known as Z-AAT. Instead of leaving the liver and doing its job, this abnormal Z-AAT protein gets trapped inside liver cells. Over time, this buildup can damage the liver, leading to problems like scarring (called fibrosis), more severe damage (cirrhosis), and eventually serious liver failure.

The new medicine being studied is called fazirsiran. Its purpose is to reduce the amount of this faulty Z-AAT protein that the liver produces. By lowering the production of this abnormal protein, the hope is to prevent or slow down its buildup in the liver, thereby reducing liver damage. This particular study is focusing on individuals with AATD who have already developed mild liver scarring. These participants will receive either fazirsiran or a placebo (an inactive substance) over about two years, allowing researchers to compare the effects.

The main goals of this study are to carefully check if fazirsiran is safe to use and if people can tolerate it well over a longer period. Researchers will also be looking to see if the medicine has any positive effects on the liver scarring. To understand this, small samples of liver tissue will be collected through a procedure called a liver biopsy at two different times during the study. This is a 'Phase 3' study, which means it's a crucial stage before a medicine might become more widely available.

Key takeaways

Investigating new medicine (fazirsiran) for genetic liver disease (AATD).
Aims to reduce liver damage by targeting abnormal protein production.
For people with mild liver scarring between 18 and 75 years old.
Will assess safety, tolerance, and effect on liver scarring over 2 years.
Involves injections (fazirsiran or placebo) and two liver biopsies.
Participation helps advance understanding of AATD treatment.

Who may be eligible?

To join this study, you would need to be between 18 and 75 years old. Doctors in the study need to confirm that you have a specific genetic type of Alpha-1 Antitrypsin Deficiency, called PiZZ. This will likely involve checking your medical records or doing a genetic test.

An important part of qualifying is having mild liver scarring. This will be confirmed by reviewing a recent liver biopsy or by having a new one done as part of the screening process. You would also need to be able to understand and follow the study instructions and fill out questionnaires.

There are also some things that would prevent you from joining. For example, if you have other specific genetic types of AATD (like PiMZ or PiSZ), if you have certain types of liver cancer, or if your lung health doesn't meet the study's requirements. If you are taking certain common medicines for conditions like high blood pressure or high cholesterol, you would need to be on a stable dose for at least 8 weeks before starting the study.

Quick self-check

Are you between 18 and 75 years old?
Do you have a confirmed diagnosis of the PiZZ type of Alpha-1 Antitrypsin Deficiency?
Have you developed mild liver scarring confirmed by a recent or planned liver biopsy?
Are you able to follow study instructions and attend regular appointments?
Do you *not* have certain types of liver cancer or severe lung problems?

This is a guide only — the research team will confirm whether you can take part.

What does participation involve?

If you join this study, you'll be involved for about two years. During this time, you'll either receive injections of the study drug, fazirsiran, or a placebo (a dummy treatment). You won't know which one you're getting, and neither will your study doctor. You'll have regular visits to the clinic so the study team can monitor your health, check how you're responding to the treatment, and ensure you're tolerating it well.

Key assessments will include blood tests, physical examinations, and regular health checks. A significant part of the study involves having a liver biopsy (where a small tissue sample is taken from your liver) at two different points during the study period. This helps the doctors understand the health of your liver and if the treatment is having any effect on scarring. There will also be follow-up appointments after you finish receiving the study medicine to ensure your well-being. The study team will provide all medication and care related to the trial.

Potential risks and benefits

Participating in a clinical trial offers potential benefits, such as access to a new treatment before it's widely available and contributing to medical knowledge that could help others. However, there are also potential risks; fazirsiran is an investigational drug, meaning its long-term effects and full safety profile are still being studied. There could be side effects from the medication or discomfort from procedures like liver biopsies and injections. It's crucial to remember that you have the right to withdraw from the study at any time, for any reason, without affecting your standard medical care.

Locations (41)

St Joseph's Hospital and Medical Center
Phoenix, United States· Recruiting
Mayo Clinic - PPDS
Phoenix, United States· Recruiting
University of Arizona Thomas D. Boyer Liver Institute
Tucson, United States· Recruiting
University of California San Diego
La Jolla, United States· Recruiting
UCLA Pulmonary and Critical Care
Los Angeles, United States· Recruiting
University of California Benioff Children's Hospital
San Francisco, United States· Recruiting
Peak Gastroenterology Associates
Colorado Springs, United States· Recruiting
Schiff Center for Liver Diseases/University of Miami
Miami, United States· Recruiting
Indiana University School of Medicine-Indianapolis
Indianapolis, United States· Recruiting
University Of Iowa Hospitals And Clinics
Iowa City, United States· Recruiting
Boston Medical Center
Boston, United States· Recruiting
University of Michigan Hospital - 1500 E Medical Center Dr
Ann Arbor, United States· Recruiting

+29 more sites — see the official record for the full list.

Common questions

What is Alpha-1 Antitrypsin Deficiency (AATD)?

It's a genetic condition where the liver makes an abnormal protein that can build up, leading to liver damage and other health problems.

What is fazirsiran supposed to do?

Fazirsiran is a medicine designed to reduce the production of the abnormal protein that causes liver damage in AATD.

What is a placebo?

A placebo is an inactive substance, like a sugar pill or saline injection, used in studies to compare against the real medicine's effects.

What is a liver biopsy and why is it needed?

A liver biopsy is when a small piece of liver tissue is taken. It's needed to check for liver scarring and to see if the treatment has any effect.

How long will the study last?

Participants will be involved for approximately two years, receiving treatment and attending appointments.

How to find out more

Takeda Contact

medinfoUS@takeda.com +1-877-825-3327 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.