A Study of Belcesiran in Patients With A1ATD-Associated Liver Disease (ESTRELLA)

  • STATUS
    Recruiting
  • End date
    Dec 1, 2023
  • participants needed
    54
  • sponsor
    Dicerna Pharmaceuticals, Inc.
Updated on 12 July 2022
alpha1-proteinase inhibitor (human)

Summary

This is a multiple dose, randomized, placebo-controlled, double-blind study of belcesiran to evaluate the safety, tolerability, PK, and PD in adult patients with PiZZ A1ATD-associated liver disease.

The study will be conducted in 2 parallel cohorts. A total of up to 27 participants may be enrolled in a single cohort. The 2 cohorts are differentiated only by the duration of the treatment period, the number of doses administered, and the timing of the end-of-treatment (EOT) liver biopsy. Participants in Cohort 1 will undergo EOT biopsy at 24 weeks, and participants in Cohort 2 will undergo EOT biopsy at 48 weeks.

Description

A1ATD-associated liver disease is a progressive Alpha-1 Antitrypsin-Deficiency Associated Liver Disease condition resulting in liver fibrosis, cirrhosis, and hepatocellular carcinoma. The lack of functional A1AT in individuals with the PiZZ genotype, in conjunction with other precipitating factors, can lead to unchecked activity of neutrophil elastases in the alveoli; causing emphysema and chronic obstructive pulmonary disease (COPD). This loss-of-function mechanism can be addressed with intravenous augmentation therapy, which aims to substitute the missing A1AT by infusing alpha-1 proteinase inhibitor (A1PI), purified from pooled human plasma.

While augmentation therapy can address the loss of A1AT in the lung, no treatment exists for the associated liver disease.

Given the severity of the disease, with approximately 10% of affected patients developing liver cirrhosis and a subgroup of those patients in need of liver transplantation, and the lack of an effective treatment that addresses the toxic hepatic "gain-of-function" mechanism, there is an urgent unmet medical need to develop a therapy that can help this particular patient population.

Details
Condition Alpha 1-Antitrypsin Deficiency
Treatment Placebo, belcesiran
Clinical Study IdentifierNCT04764448
SponsorDicerna Pharmaceuticals, Inc.
Last Modified on12 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

to 70 years, inclusive. Female participants must be either surgically sterile or postmenopausal. No women of childbearing potential are eligible for enrollment
Documented diagnosis of PiZZ-type A1ATD, confirmed by genotyping. Historical genotyping data may be used, if available
A1ATD-associated liver disease documented by liver biopsy
Consent to undergo paired liver biopsies, one at Screening and one at either 24 weeks or 48 weeks of the first dose of the study intervention
Lung, renal and liver function within acceptable limits
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol

Exclusion Criteria

Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially affect patient safety including, but not restricted to
Severe intercurrent illness
History of chronic liver disease from any cause other than PiZZ-type A1ATD
A1AT augmentation therapy in the 6 months prior to Screening
Routine use of acetaminophen/paracetamol
Use of systemically acting steroids in the month prior to Screening and throughout the study period
Participation in any clinical study in which they received an IMP within 4 months before Screening
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note