Study of DCR-A1AT in Healthy Adult Volunteers
- Registration Number
- NCT04174118
- Lead Sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Healthy volunteers will be administered a single dose of matching placebo. belcesiran belcesiran Healthy volunteers will be administered a single dose of belcesiran.
- Primary Outcome Measures
Name Time Method Safety and tolerability approximately up to 2 months The incidence of adverse events (AE), serious adverse events (SAE), DLT, and AE leading to study drug discontinuation
Evaluating safety and tolerability through physical exams approximately up to 2 months The incidence of clinically significant physical examination (PE) findings
Changes in 12-lead electrocardiograms (ECG) approximately up to 2 months Absolute QTc \> 500 msec and/or QTc change of \> 60 msec from baseline will be evaluated
- Secondary Outcome Measures
Name Time Method Plasma pharmacokinetics (PK) of belcesiran up to 57 days Time to maximum concentration (Tmax)
Plama pharmacokinetics (PK) of belcesiran up to 57 days Terminal elimination half-life (t1/2)
Change in protein concentration up to day 57 Changes in A1AT protein concentrations
Urine pharmacokinetics (PK) of belcesiran up to Day 3 Terminal elimination half-life (t1/2)
Trial Locations
- Locations (2)
Clinical Trial Consultants AB
🇸🇪Uppsala, Sweden
Auckland Clinical Studies
🇳🇿Grafton, Auckland, New Zealand