Study of DCR-A1AT in Healthy Adult Volunteers

NCT ID: NCT04174118

Last Updated: 2024-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-24
• Study Completion Date: 2023-03-06

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

belcesiran

Healthy volunteers will be administered a single dose of belcesiran.

Group Type: EXPERIMENTAL

belcesiran

Intervention Type: DRUG

belcesiran will be administered subcutaneously (SC) at dose levels planned.

Placebo

Healthy volunteers will be administered a single dose of matching placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sterile normal saline (0.9% NaCL) matching volume of belcesiran doses will be administered subcutaneously (SC).

Interventions

belcesiran

belcesiran will be administered subcutaneously (SC) at dose levels planned.

Intervention Type: DRUG

Placebo

Sterile normal saline (0.9% NaCL) matching volume of belcesiran doses will be administered subcutaneously (SC).

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Bowman, MD

Role: STUDY_DIRECTOR

Dicerna Pharmaceuticals

Locations

Auckland Clinical Studies

Grafton, Auckland, New Zealand

Clinical Trial Consultants AB

Uppsala, , Sweden

Countries

New Zealand; Sweden

References

Remih K, Amzou S, Strnad P. Alpha1-antitrypsin deficiency: New therapies on the horizon. Curr Opin Pharmacol. 2021 Aug;59:149-156. doi: 10.1016/j.coph.2021.06.001. Epub 2021 Jul 10.

Reference Type: DERIVED

PMID: 34256305 (View on PubMed)

Other Identifiers

DCR-A1AT-101

Identifier Type: -

Identifier Source: org_study_id