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
plasma.
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
Interventional
Primary Outcome
Safety and tolerability
Secondary Outcome
Urine pharmacokinetics (PK) of belcesiran
Condition
Alpha 1-Antitrypsin Deficiency
Intervention
belcesiran
Study Arms / Comparison Groups
belcesiran
Description: Healthy volunteers will be administered a single dose of belcesiran.
Publications
* 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
Drug
Estimated Enrollment
36
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
(HBV)
- Serum creatinine or estimated glomerular filtration rate (eGFR) outside normal
reference ranges.
Gender
All
Ages
18 Years - 55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Hardean Achneck, MD, 617-621-8097, [email protected]
Location Countries
New Zealand
Location Countries
New Zealand
Administrative Informations
NCT ID
NCT04174118
Organization ID
DCR-A1AT-101
Responsible Party
Sponsor
Study Sponsor
Dicerna Pharmaceuticals, Inc.
Study Sponsor
Hardean Achneck, MD, Study Director, Dicerna Pharmaceuticals
Verification Date
January 2021