Study of DCR-A1AT in Healthy Adult Volunteers

NCT04174118 | Completed Phase 1 DMC

• 1 other identifier: DCR-A1AT-101
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 2

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability

  The incidence of adverse events (AE), serious adverse events (SAE), DLT, and AE leading to study drug discontinuation

  approximately up to 2 months

• Evaluating safety and tolerability through physical exams

  The incidence of clinically significant physical examination (PE) findings

  approximately up to 2 months

• Changes in 12-lead electrocardiograms (ECG)

  Absolute QTc \> 500 msec and/or QTc change of \> 60 msec from baseline will be evaluated

  approximately up to 2 months

Secondary Outcomes (11)

• Urine pharmacokinetics (PK) of belcesiran

  up to Day 3

• Plasma pharmacokinetics (PK) of belcesiran

  up to 57 days

• Plasma pharmacokinetics (PK) of belcesiran

  up to 57 days

• Urine pharmacokinetics (PK) of belcesiran

  up to Day 3

• Urine pharmacokinetics (PK) of belcesiran

  up to Day 3

Study Arms (2)

belcesiran

EXPERIMENTAL

Healthy volunteers will be administered a single dose of belcesiran.

Drug: belcesiran

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

belcesiran DRUG

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

belcesiran

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dicerna Pharmaceuticals, Inc., a Novo Nordisk company: lead

Study Sites (2)

Auckland Clinical Studies

Grafton, Auckland, 1010, New Zealand

Location

Clinical Trial Consultants AB

Uppsala, Sweden

Location

Related Publications (1)

• 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.

  PMID: 34256305 DERIVED

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas Bowman, MD

  Dicerna Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2019
• First Posted: November 22, 2019
• Study Start: October 24, 2019
• Primary Completion: July 6, 2021
• Study Completion: March 6, 2023
• Last Updated: November 6, 2024

Record last verified: 2024-09

Locations

NZ (1); SE (1)