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

  • End date
    Dec 1, 2023
  • participants needed
  • sponsor
    Dicerna Pharmaceuticals, Inc.
Updated on 4 October 2022
alpha1-proteinase inhibitor (human)


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.


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.

Condition Alpha 1-Antitrypsin Deficiency
Treatment Placebo, belcesiran
Clinical Study IdentifierNCT04764448
SponsorDicerna Pharmaceuticals, Inc.
Last Modified on4 October 2022


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
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