A Study of DCR-A1AT in Healthy Adult Volunteers and Patients With A1ATD-Associated Liver Disease

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Brief Title

Study of DCR-A1AT in Healthy Adult Volunteers

Official Title

A Phase 1 Single Ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered Belcesiran in Healthy Adult Volunteers

Brief Summary

      This is a research study to test an experimental study drug (belcesiran, also known as
      DCR-A1AT). This drug is being tested to see if it helps people with a rare condition known as
      Alpha-1 Antitrypsin Deficiency, or A1ATD. Prior to initiation of this study belcesiran had
      not yet been tested in humans. All study participants will be randomly assigned to either
      receive the study drug or a placebo. This will allow for the sponsor to compare the effects
      of the study drug with that of the placebo. A placebo looks like the study drug but does not
      contain any of the study drug.

      The main purpose of the first part of the study is to evaluate the safety profile of the
      study drug in people who do not have A1ATD. This part of the study will also help find the
      dose of the study drug that has an acceptable safety profile for testing.

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 PiZZ genotype, in conjunction with other
      precipitating factors, can lead to unchecked activity in 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 alpha1 proteinase inhibitor (A1PI), purified from pooled human

      While augmentation therapy can address the loss of A1AT in the lungs, 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 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 in this particular
      patient population.

Study Phase

Phase 1

Study Type


Primary Outcome

Safety and tolerability

Secondary Outcome

 Urine pharmacokinetics (PK) of belcesiran


Alpha 1-Antitrypsin Deficiency



Study Arms / Comparison Groups

Description:  Healthy volunteers will be administered a single dose of 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

October 24, 2019

Completion Date

June 2022

Primary Completion Date

December 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Male or Female aged 18 to 55 years, inclusive. Female participants must be either
             surgically sterile or postmenopausal. No women of childbearing potential are eligible
             for enrollment.

          -  Overtly Healthy, as determined by the investigator.

          -  Serum A1AT protein concentration >100 mg/dL

          -  Adequate forced expiratory volume in one second (FEV1) and adequate FEV1/forced vital
             capacity (FVC) ratio

          -  Non-smokers with a <2 pack-year history and smoking cessation for at least 6 months
             with a negative urinary cotinine test a screening

        Exclusion Criteria:

          -  Presence of any condition or comorbidities that would interfere with study compliance
             or data interpretation or potentially affect participant safety

          -  Clinically significant abnormal laboratory tests

          -  Received an experimental drug within past 4 months

          -  Prior to use of RNAi drug or oligonucleotide-based therapy

          -  Known human immunodeficiency virus (HIV), hepatitis C virus (HCV), or Hepatitis B

          -  Serum creatinine or estimated glomerular filtration rate (eGFR) outside normal
             reference ranges.




18 Years - 55 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers


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

Location Countries

New Zealand

Location Countries

New Zealand

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Dicerna Pharmaceuticals, Inc.

Study Sponsor

Hardean Achneck, MD, Study Director, Dicerna Pharmaceuticals

Verification Date

January 2021