Study of DCR-AUD in Healthy Volunteers

NCT ID: NCT05021640

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-21
• Study Completion Date: 2022-12-31

Brief Summary

DCR-AUD will be evaluated for safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers.

Detailed Description

DCR-AUD is being developed for the treatment of alcohol use disorder (AUD) in adults using an RNA interference (RNAi) technology platform. This is a 24-week, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of single-ascending doses (SAD) of DCR-AUD administered to adult HVs. The single doses of DCR-AUD will be administered to adult HVs across 4 sequential cohorts (3 planned [80 mg, 240 mg, 480 mg] and one optional [960 mg]). Each cohort will comprise a sentinel group of 3 participants (2 active, 1 placebo) and an expanded group of 6 participants (4 active, 2 placebo). The sentinel group will be followed for the assessment of safety and tolerability and characterization of PK but who will not undergo any EIAs. Participants will receive a single dose of study intervention on Day 1 and will be followed for 24 weeks. Participants who have positive ethanol reaction symptoms at the Day 169 EIA (e.g., nausea, vomiting, or substantial flushing) will return every 28 (±7) days for follow-up EIAs until the positive ethanol reaction symptoms abate. These conditional follow-up (CFU) EIAs will not require overnight admission to the clinic, but all other aspects of the EIA will be conducted (see Table 3). Participants will be observed for not less than 6 hours after ethanol administration and will not be discharged until the Investigator deems it medically safe to do so.

Conditions

Alcohol Use Disorder (AUD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort 1: DCRAUD 80 mg

Participant received a single dose of DCR-AUD 80 mg, subcutaneous injection on Day 1.

Group Type: EXPERIMENTAL

DCR-AUD

Intervention Type: DRUG

DCR-A1203, the drug substance of DCR-AUD, is a synthetic double-stranded (hybridized duplex) RNA oligonucleotide conjugated to GalNAc ligands that enable specific hepatic access and uptake after subcutaneous administration. DCR-AUD is a sterile solution of DCR-A1203 at a concentration of 160 mg/mL in water for injection (WFI).

Cohort 2: DCRAUD 240 mg

Participant received a single dose of DCR-AUD 240 mg, subcutaneous injection on Day 1.

Group Type: PLACEBO_COMPARATOR

DCR-AUD

Intervention Type: DRUG

DCR-A1203, the drug substance of DCR-AUD, is a synthetic double-stranded (hybridized duplex) RNA oligonucleotide conjugated to GalNAc ligands that enable specific hepatic access and uptake after subcutaneous administration. DCR-AUD is a sterile solution of DCR-A1203 at a concentration of 160 mg/mL in water for injection (WFI).

Cohort 3: DCR-AUD 480 mg

Participant received a single dose of DCR-AUD 480 mg, subcutaneous injection on Day 1.

Group Type: EXPERIMENTAL

DCR-AUD

Intervention Type: DRUG

DCR-A1203, the drug substance of DCR-AUD, is a synthetic double-stranded (hybridized duplex) RNA oligonucleotide conjugated to GalNAc ligands that enable specific hepatic access and uptake after subcutaneous administration. DCR-AUD is a sterile solution of DCR-A1203 at a concentration of 160 mg/mL in water for injection (WFI).

Cohort 4: DCR-AUD 960 mg

Participant received a single dose of DCR-AUD 960 mg, subcutaneous injection on Day 1.

Group Type: PLACEBO_COMPARATOR

DCR-AUD

Intervention Type: DRUG

DCR-A1203, the drug substance of DCR-AUD, is a synthetic double-stranded (hybridized duplex) RNA oligonucleotide conjugated to GalNAc ligands that enable specific hepatic access and uptake after subcutaneous administration. DCR-AUD is a sterile solution of DCR-A1203 at a concentration of 160 mg/mL in water for injection (WFI).

Pooled Placebo

Participant received a single dose of DCR-AUD matching placebo, subcutaneous injection on Day 1.

Group Type: EXPERIMENTAL

Placebo for DCR-AUD

Intervention Type: DRUG

0.9% saline for injection

Interventions

DCR-AUD

DCR-A1203, the drug substance of DCR-AUD, is a synthetic double-stranded (hybridized duplex) RNA oligonucleotide conjugated to GalNAc ligands that enable specific hepatic access and uptake after subcutaneous administration. DCR-AUD is a sterile solution of DCR-A1203 at a concentration of 160 mg/mL in water for injection (WFI).

Intervention Type: DRUG

Placebo for DCR-AUD

0.9% saline for injection

Intervention Type: DRUG

Other Intervention Names

DCR-A1203; Placebo

Eligibility Criteria

Inclusion Criteria

• Male and female participants, between 21 and 65 years of age (inclusive), who were social drinkers of modest amounts of alcohol (less than or equal to (≤) 2 drinks/day, ≤ 3 days/week) and would be able to refrain from drinking alcohol during the outpatient portion of the trial
• Overtly healthy, as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Negative screen for drugs of abuse (to include at minimum: amphetamines, barbiturates, cocaine, opioids, and benzodiazepines) at Screening and Day 1. Cannabis will not be recorded as a drug of abuse for this study.
• Had a negative test for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection on Day -1 and prior to admission to the clinical unit.
• Systolic BP in the range of 90 to 140 millimetre(s) of mercury (mmHg) and diastolic BP in the range of 50 to 95 mmHg, and body mass index (BMI) within the range of 18.0 to 32.0 kilogram per square meter (kg/m^2) (inclusive).

Exclusion Criteria

• History of any medical condition that may interfere with the absorption, distribution, or elimination of study intervention, or with the clinical and laboratory assessments in this study, including (but not limited to): chronic or recurrent renal disease, functional bowel disorders (e.g., frequent diarrhea or constipation), clinically significant cardiovascular or pulmonary disease or has cardiovascular or pulmonary disease requiring pharmacologic medication, GI tract disease, pancreatitis, seizure disorder, mucocutaneous, or musculoskeletal disorder.
• Any history of severe or recent clinically significant depression, anxiety, bipolar disorder, schizophrenia, or other neuropsychiatric disorder that, in the judgment of the Investigator, represents a safety risk to the individual were they to participate in the trial
• History of delirium tremens or alcohol-related seizures.
• History of significant adverse reaction(s) to alcohol.
• History of substance use disorder (SUD), including alcohol (AUD) or illicit drug use (excluding cannabis) within the preceding 12 months. Nicotine use is permitted.
• History of any concomitant medical condition for which alcohol consumption is prohibited or advised against by the participant's physician or health care provider.
• History of multiple drug allergies or a history of allergic reaction to an oligonucleotide based therapy

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 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

Clinical Transparency (dept. 1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Parexel Los Angeles Early Phase Clinical Unit

Glendale, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U44AA027404

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DCR-AUD-101

Identifier Type: -

Identifier Source: org_study_id