Fazirsiran for Alpha-1 Antitrypsin Deficiency

Recruiting at 88 trial locations

Overseen By Arpan Mohanty

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Disqualifiers: Liver decompensation, Chronic liver diseases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 107

Duration: 196 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called fazirsiran (an injection) to determine if it can reduce liver scarring and slow liver disease in people with Alpha-1 Antitrypsin Deficiency (AATD). Participants will receive either fazirsiran or a placebo and undergo two liver biopsies to check for improvements. The study seeks participants diagnosed with AATD and liver fibrosis, a condition where the liver becomes scarred and functions improperly. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that fazirsiran is likely to be safe for humans?

Research has shown that fazirsiran has been tested for safety and effectiveness in people with Alpha-1 Antitrypsin Deficiency. In these studies, fazirsiran was generally well-tolerated. Specifically, one study found that 58% of patients experienced a reduction in liver scarring, and there was an 83% decrease in harmful protein build-up in the liver. These findings suggest that fazirsiran may be safe to use, as it did not cause severe side effects in most patients.

However, like any treatment, fazirsiran can have side effects. The specific side effects were not detailed in the sources, but ongoing research aims to better understand its long-term safety. Since fazirsiran is in a later phase of clinical trials, earlier trials have already shown some evidence that it is safe for further testing in more people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fazirsiran is unique because it targets the root cause of Alpha-1 Antitrypsin Deficiency by using RNA interference (RNAi) technology to reduce the production of the faulty protein responsible for the condition. Unlike standard treatments that mainly focus on managing symptoms or replacing the missing protein, Fazirsiran offers a new approach by addressing the genetic source of the problem. Researchers are excited about this treatment because it has the potential to significantly improve lung function and slow disease progression by directly reducing the harmful protein levels in the body.

What evidence suggests that fazirsiran might be an effective treatment for Alpha-1 Antitrypsin Deficiency?

Research has shown that fazirsiran, which participants in this trial may receive, may help treat liver problems caused by Alpha-1 Antitrypsin Deficiency. One study found that 58% of patients experienced a noticeable reduction in liver scarring after taking fazirsiran. The same study also reported an 83% decrease in the harmful Z-AAT protein that accumulates in the liver. Another study demonstrated that fazirsiran could lower Z-AAT levels in the blood by up to 94% at higher doses. These findings suggest that fazirsiran might effectively reduce liver damage and improve liver health in patients. ^{1 2 4 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults aged 18-75 with Alpha-1 Antitrypsin Deficiency (AATD) causing liver scarring, who are non-smokers for at least a year and have a BMI of 18.0-39.0 kg/m2 can join this trial. They must not have liver cancer, drug abuse history within the last year, certain blood or liver issues, other chronic liver diseases, recent malignancies except some skin cancers or in situ cervical cancer.

Inclusion Criteria

My BMI is between 18.0 and 39.0.

I have been diagnosed with the PiZZ genotype for AATD.

My liver fibrosis is at stage F2, F3, or F4 based on a recent biopsy.

Exclusion Criteria

I have had medium or large varices, or ones with red signs, but small ones without bleeding are okay.

I had cancer in the last 5 years, but it was either skin cancer, superficial bladder tumors, or in situ cervical cancer, or I've been disease-free for over a year.

I have been treated with RNAi therapy for AATD-LD before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fazirsiran or placebo via subcutaneous injection on Day 1, at Week 4, and then every 12 weeks thereafter up to Week 196

196 weeks

Injections on Day 1, Week 4, and every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including liver biopsies and assessments of liver function and fibrosis

34 weeks

Liver biopsies and assessments at Week 106, Week 202, and up to Week 230

What Are the Treatments Tested in This Trial?

Interventions

• Fazirsiran Injection
• Placebo

Trial Overview The study is testing if Fazirsiran injections can reduce liver scarring compared to placebo in people with AATD-related fibrosis. It will also assess how the body processes Fazirsiran and its impact on disease progression using biopsies and biomarkers.

How Is the Trial Designed?

Group I: Fazirsiran Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo on Day 1, at Week 4, and Q12 W thereafter up to Week 196.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Citations

1. takeda.com takeda.com/newsroom/newsreleases/2022/results-from-phase-2-study-of-fazirsiran-in-patients-with-alpha-1-antitrypsin-deficiency-published-in-new-england-journal-of-medicine/

Results from Phase 2 Study of Fazirsiran in Patients with ... Fibrosis regression observed in 58% (7 of 12) of patients receiving 200 mg fazirsiran; Median reduction of 83% of Z-AAT accumulation in the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05677971

NCT05677971 | Study to Check the Safety of Fazirsiran ... 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38964420/

Fazirsiran for Adults With Alpha-1 Antitrypsin Deficiency ... Results: At week 16, least-squares mean percent declines in serum Z-AAT concentration were -61%, -83%, and -94% with fazirsiran 25, 100, and 200 mg, ...

4. ir.arrowheadpharma.com ir.arrowheadpharma.com/static-files/071c3533-3265-46f3-be7d-951b13aac69e

long-term safety and efficacy of fazirsiran in patients with ... In the fazirsiran 200 mg open-label extension, there was a trend towards improved laboratory measures of liver health, stable pulmonary function ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-long-term-safety-of-fazirsiran-for-patients-with-alpha-1-antitrypsin-deficiency-related-liver-disease/

Study on Long-Term Safety of Fazirsiran for Patients with ... The purpose of this study is to evaluate the long-term safety and effectiveness of Fazirsiran in people with Alpha-1 Antitrypsin Deficiency- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03945292

Study Details | NCT03945292 | Safety, Tolerability and ... The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, efficacy and tolerability of multiple doses of the investigational product, Fazirsiran Injection.