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

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Brief Title

A Study of Belcesiran in Patients With AATLD

Official Title

A Phase 2, Randomized, Double-blind, Placebo-Controlled Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Two Dose Levels of Belcesiran in Patients With Alpha-1 Antitrypsin Deficiency-Associated Liver Disease

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 AATD-associated
      liver disease (AATLD).

      The study will be conducted in 3 separate cohorts. A total of up to 16 participants may be
      enrolled in Cohort 1 and 2. A total number of 30 subjects will be enrolled in cohort 3. The 3
      cohorts are differentiated by the duration of the treatment period, the number of doses
      administered, and the timing of the second liver biopsy.

Detailed Description

      AATD-associated liver disease is a progressive condition resulting in liver fibrosis,
      cirrhosis, and in some cases hepatocellular carcinoma. The lack of functional alpha-1
      antitrypsin (AAT) 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 may be addressed by use of intravenous augmentation therapy, which aims to
      substitute the missing AAT by infusing alpha-1 proteinase inhibitor (A1PI), purified from
      pooled human plasma.

      While augmentation therapy can address the loss of AAT 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 and nature of treatment emergent adverse events (TEAE)


Alpha 1-Antitrypsin Deficiency



Study Arms / Comparison Groups

 Belcesiran Cohort 1


* 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, 2026

Primary Completion Date

September 30, 2023

Eligibility Criteria

        Inclusion Criteria:

          -  18 to 75 years, inclusive, at the time of consent.

          -  Documented diagnosis of PiZZ-type alpha-1 antitrypsin deficiency, confirmed by
             genotyping. Historical genotyping data may be used, if available.

          -  AATD-associated liver disease documented by liver biopsy at Screening.

          -  Consent to undergo paired liver biopsies.

          -  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:

          -  History of chronic liver disease other than non-alcoholic fatty liver disease from any
             cause other than PiZZ-type alpha-1 antitrypsin deficiency.

          -  Child-Pugh Score B or C.

          -  History of one single severe exacerbation of underlying lung disease in the year prior
             to randomization.

          -  History of clinically significant respiratory infections (including pneumonia and
             lower respiratory tract infections), as determined by the Investigator, in the 3
             months prior to screening

          -  Use of an RNAi drug at any time.




18 Years - 75 Years

Accepts Healthy Volunteers



Thomas Bowman, MD, 617-621-8097, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Dicerna Pharmaceuticals, Inc.

Study Sponsor

Thomas Bowman, MD, Study Director, Dicerna Pharmaceuticals / Novo Nordisk

Verification Date

November 2022