Phase 1b Study of DCR-AUD in Healthy Volunteers

NCT05845398 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: DCR-AUD-102
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of of repeat doses of DCR-AUD in adult healthy volunteers who are social drinkers. The main questions it aims to answer are:

• Are repeat doses of DCR-AUD safe and well-tolerated in healthy adults who are social drinkers?
• How does the drug behave inside the human body and how it is removed from the human body?
• What are the symptoms the drug may cause with alcohol consumption? Participants will:
• Receive multiple doses of DCR-AUD.
• Have assessment visits through Week 24.
• Participate in up to 10 Ethanol Interaction Assessments (EIAs) to see how the body is affected by DCR-AUD. Researchers will compare the groups of participates who receive study drug with the group of participants who receive placebo to see if the study drug is safe and tolerable and whether the study drug has any real effect.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  An Adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. A TEAE is defined as an AE that begins or that worsens in severity after the study drug has been administered. An SAE is defined as any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly /birth defect, is the other important medical event.

  From Day 1 up to 24 Weeks

• Number of Participants With Severity Grades of TEAEs

  An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A TEAE is defined as an AE that begins or that worsens in severity after the study drug has been administered. As per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated; Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living; Grade 3: severe or medically significant but not immediately lifethreatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4: life-threatening consequences; urgent treatment indicated; Grade 5: fatal.

  From Day 1 up to 24 Weeks

• Number of Participants With Change From Baseline in Clinically Significant Abnormal Vital Signs

  Number of participants with change from baseline in clinically significant abnormal vital signs (temperature, pulse rate, respiratory rate, and blood pressure) is presented.

  From Baseline (Day -1) up to 24 weeks

• Number of Participants With Change From Baseline in Clinically Significant Abnormal Electrocardiogram (ECG)

  Number of participants with change from baseline in clinically significant abnormal ECG findings (Heart rate, PR interval, QRS interval, QT interval and QT interval using Fridericia's correction \[QTcF\]) is presented.

  From Baseline (Day -1) up to 24 weeks

• Number of Participants With Change From Baseline in Clinically Significant Abnormal Laboratory Values

  Number of participants with change from baseline in clinically significant abnormal laboratory values (hematology, clinical chemistry, coagulation and routine urinalysis parameters) is presented.

  From Baseline (Day -1) up to 24 weeks

• Number of Participants With Change From Baseline in Clinically Significant Physical Examination Findings

  Number of participants with change from baseline in clinically significant physical examination findings (assessments of the cardiovascular, respiratory, gastrointestinal, neurological, and skin systems and inspection of the injection site) is presented.

  From Baseline (Day -1) up to 24 weeks

Secondary Outcomes (8)

• Six Symptom Responses During Ethanol Interactions Assessments (EIAs)

  Day -1 (baseline), Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 112, Day 140 and Day 168

• AUC0-last: Area Under the Plasma Concentration Curve From Time Zero to the Last Quantifiable Concentration of DCR-AUD

  Day 1, Day 29 and Day 57

• Cmax: Maximum Observed Plasma Concentration of DCR-AUD

  Day 1, Day 29 and Day 57

• Tmax: Time to Reach the Maximum Plasma Concentration of DCR-AUD (Cmax)

  Day 1, Day 29 and Day 57

• Cmax: Maximum Observed Plasma Concentration of Acetaldehyde

  Day -1 (baseline), Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 112, Day 140 and Day 168

Study Arms (2)

DCR-AUD

EXPERIMENTAL

Multiple doses of DCR-AUD. Subcutaneous administration of of DCR-AUD.

Drug: DCR-AUD

DCR-AUD Placebo

PLACEBO COMPARATOR

Multiple doses of placebo comparator. Subcutaneous administration of Placebo for DCR-AUD, volume to match active single dose

Drug: Placebo

Interventions

DCR-AUD 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 update after subcutaneous administration. DCR-AUD is a sterile solution of DCR-A1203 at a concentration of 160 mg/mL in water for injection (WFI).

Also known as: DCR-A1203

DCR-AUD

Placebo DRUG

0.9% saline for injection.

DCR-AUD Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 65 years, inclusive, at the time of signing informed consent.
• Overtly healthy volunteers, as determined by medical evaluation including medical history, physical examination, and laboratory testing.
• No diagnosis of AUD within the preceding 12 months per Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
• Social drinkers who consume, on average, 5 to 20 drinks per week for men or 5 to 14 drinks per week for women over the 4 weeks prior to Screening, and not more than 8 drinks in a single day.
• No evidence of overt or sub-clinical hepatic pathology, as manifest by serologic tests demonstrating hepatic inflammation or compromised hepatic synthetic function (i.e., AST, ALT, GGT, total bilirubin \< 1.5 times the ULN at Screening and Day -1).
• eGFR ≥ 60 mL/min/1.73 m2 at Screening.
• No history of significant adverse reaction(s) to alcohol. Participant should be expected to tolerate the amount of alcohol administered during EIAs.
• Willing to participate in up to 10 EIAs.
• Has a negative test for SARS-CoV-2 infection on Day -1.
• Systolic BP in the range of 80 to 140 mmHg and diastolic BP in the range of 50 to 95 mmHg at Screening. If out of range, BP may be repeated once at the discretion of the Investigator.
• Male or female
• Male participants with partners of childbearing potential must agree to use contraception from Screening through at least 24 weeks after the last dose of study intervention and refrain from donating sperm during this period (see Section 10.4).
• Female participants may not be pregnant or breastfeeding, and at least one of the following conditions must apply:
• Is not a woman of childbearing potential (WOCBP) or
• If a WOCBP, must agree to follow the contraceptive guidance (see Section 10.4), beginning at consent and the first Screening visit and for at least 24 weeks after the last dose of study intervention.

You may not qualify if:

• History of any medical condition that may interfere with the metabolism of study intervention or with the clinical and laboratory assessments in this study. 2. History of serious, persistent medical conditions, including liver, gastrointestinal, pulmonary, renal, or cardiovascular abnormalities. 3. History of suicidal attempt at any time or an answer of "yes" on any of the following items in the C-SSRS at Screening:
• Items 1 or 2 of the Suicidal Ideation section, if ideation occurred in the previous 12 months.
• Items 4 or 5 of the Suicidal Ideation section, in lifetime.
• Any item of the Suicidal Behavior section of the C-SSRS, in lifetime. 4. Any history of severe or recent clinically significant depression, anxiety, bipolar disorder, schizophrenia, or other neuropsychiatric disorder that, in the judgement of the Investigator, represents a safety risk to the participant were they to participate in the trial, as informed by the participant's medical history and/or responses to the MINI Screen Questionnaire. 5. History of substance use disorder (SUD) or illicit drug use (excluding cannabis) within the preceding 12 months. 6. History of alcohol withdrawal symptoms including delirium tremens or alcohol-related seizures. 7. Any condition that, in the opinion of the Investigator, would make the participant unsuitable for participation or could interfere with participation in or completion of the study, including:
• a. Poorly controlled or unstable hypertension. b. Diabetes mellitus treated with insulin or hypoglycemic agents (including metformin) or HbA1C \> 7%. Asthma requiring hospital admission within the preceding 12 months. NOTE: Persons with clinically stable asthma who have not been hospitalized in the prior year and are treated only with orally inhaled medications are not excluded. d. Currently poorly controlled endocrine conditions, except for hypothyroidism that is stable (no treatment change in prior 6 months). e. Significant infection or known systemic inflammatory process ongoing at Screening.
• f. History of chronic or recurrent UTI, or UTI within 1 month prior to Screening.
• \. History of malignancy within the preceding 5 years requiring treatment, with the exception of excised low grade basal cell skin neoplasms. 9. History of any concomitant medical condition for which alcohol consumption is prohibited or advised against by the participant's physician or health care provider.
• \. SARS-CoV-2 infection in the 14 days prior to randomization. 11. Clinically significant illness within the 7 days prior to the first administration of study intervention. History of multiple drug allergies or a history of allergic reaction to an oligonucleotide based therapy.
• \. Donation of \> 500 mL of blood within the 2 months prior to administration of study intervention or donation of plasma within 7 days prior to Screening.
• Life Style Considerations:
• Study participants are to refrain from drinking alcohol for 24 hours prior to each EIA and must have a negative breath-alcohol test on the day of the study visit.
• Study participants will be advised to avoid consuming more than 4 drinks during any drinking session outside of in-clinic EIAs.
• Study participants will be instructed to stop drinking at the onset of any ethanol reaction symptoms during outside drinking sessions.
• Tobacco/nicotine use is not restricted.
• Study participants are to refrain from using cannabis for 24 hours prior to each EIA and must have a negative urine-drug test on the day of the study visit.

Sponsors & Collaborators

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

Study Sites (1)

Parexel Los Angeles Early Phase Clinical Unit

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Alcoholism

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

clinicaltrials@novonordisk.com

866-867-7178

Study Officials

• John Hanrahan, MD, MPH

  Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

  STUDY DIRECTOR

• Lev G. Gertsik, MD

  Parexel

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and site study staff will be blinded to the randomization. Some members of the Sponsor team will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 3 to 1 to DCR-AUD or placebo.

Study Record Dates

• First Submitted: April 26, 2023
• First Posted: May 6, 2023
• Study Start: January 29, 2023
• Primary Completion: August 22, 2023
• Study Completion: August 22, 2023
• Last Updated: January 14, 2026
• Results First Posted: January 3, 2025

Record last verified: 2025-12

Locations

US (1)