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

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Brief Title

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

Official Title

A Phase 2a, Randomized, Double-blind, Placebo Controlled, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of Belcesiran in Patients With PiZZ Alpha-1 Antitrypsin Deficiency

Brief 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.

Detailed 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

      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.

Study Phase

Phase 2

Study Type


Primary Outcome

The incidence of adverse events (AE), serious adverse events (SAE), and AE leading to study drug discontinuation.

Secondary Outcome

 Plasma concentration of Belcesiran on Day 1


Alpha 1-Antitrypsin Deficiency



Study Arms / Comparison Groups

 Experimental: belcesiran
Description:  Patients diagnosed with A1ATD-Associated Liver Disease will be administered belcesiran.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

February 12, 2021

Completion Date

December 1, 2023

Primary Completion Date

December 1, 2022

Eligibility Criteria

        Inclusion Criteria:

          -  18 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




18 Years - 70 Years

Accepts Healthy Volunteers



Hardean Achneck, MD, 617-621-8097, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Dicerna Pharmaceuticals, Inc.

Study Sponsor

Hardean Achneck, MD, Study Director, Dicerna Pharmaceuticals

Verification Date

December 2021