Study of DCR-AUD in Healthy Volunteers

December 2, 2024 updated by: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

A Phase 1, Double-blind, Placebo-controlled, Single-ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of DCR-AUD in Healthy Volunteers

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Glendale, California, United States, 91206
        • Parexel Los Angeles Early Phase Clinical Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1: DCRAUD 80 mg
Participant received a single dose of DCR-AUD 80 mg, subcutaneous injection on Day 1.
Drug: 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).
Other Names:
  • DCR-A1203
Placebo Comparator: Cohort 2: DCRAUD 240 mg
Participant received a single dose of DCR-AUD 240 mg, subcutaneous injection on Day 1.
Drug: 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).
Other Names:
  • DCR-A1203
Experimental: Cohort 3: DCR-AUD 480 mg
Participant received a single dose of DCR-AUD 480 mg, subcutaneous injection on Day 1.
Drug: 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).
Other Names:
  • DCR-A1203
Placebo Comparator: Cohort 4: DCR-AUD 960 mg
Participant received a single dose of DCR-AUD 960 mg, subcutaneous injection on Day 1.
Drug: 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).
Other Names:
  • DCR-A1203
Experimental: Pooled Placebo
Participant received a single dose of DCR-AUD matching placebo, subcutaneous injection on Day 1.
Drug: Placebo for DCR-AUD
0.9% saline for injection
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From Day 1 up to 24 Weeks
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
Time Frame: From Day 1 up to 24 Weeks
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 life-threatening; 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 Dose-limiting Toxicities (DLTs) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time Frame: From Day 1 up to 24 Weeks
DLT is defined as an AE of greater than or equal to (>=) Grade 3 intensity (CTCAE Version 5.0) in one participant, unless it is clearly the result of a non-study-related event OR any 2 AEs of >= Grade 2 intensity in the same body system in one participant.
From Day 1 up to 24 Weeks
Number of Participants With Change From Baseline in Clinically Significant Abnormal Vital Signs
Time Frame: From Baseline (Day -1) up to 24 weeks
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) Findings
Time Frame: From Baseline (Day -1) up to 24 weeks
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
Time Frame: From Baseline (Day -1) up to 24 weeks
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
Time Frame: From Baseline (Day -1) up to 24 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
AUC0-last: Area Under the Plasma Concentration Curve From Time Zero to the Last Quantifiable Concentration of DCR-AUD
Time Frame: Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose
AUC0-last is defined as the area under the plasma concentration curve from time zero to the last quantifiable concentration of DCR-AUD.
Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose
Cmax: Maximum Observed Plasma Concentration of DCR-AUD
Time Frame: Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose
Cmax is defined as maximum observed plasma concentration of DCR-AUD during a dosing interval.
Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose
Tmax: Time to Reach the Maximum Plasma Concentration of DCR-AUD (Cmax)
Time Frame: Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose
Tmax is defined as time to reach the maximum plasma concentration (Cmax) of DCR-AUD.
Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose
t1/2: Apparent Terminal Elimination Half-life of DCR-AUD
Time Frame: Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose
t1/2 is defined as apparent terminal elimination half-life of DCR-AUD.
Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose
Fe%0-72: Urinary Cumulative Excretion as % of Unchanged DCR-AUD up to 72 Hours
Time Frame: At time interval between 0- 4 hours, 0- 8 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours
Urinary cumulative excretion as % of DCR-AUD at each interval collection (0- 4 hours, 0- 8 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours) is reported in this outcome measure.
At time interval between 0- 4 hours, 0- 8 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours
CLR: Renal Clearance of the DCR-AUD From Plasma
Time Frame: Day 1: 0-4, 4-8, 8-12, 12-24, 24-48, and 48-72-hours post-dose
Renal clearance of the DCR-AUD from plasma is reported in this outcome measure.
Day 1: 0-4, 4-8, 8-12, 12-24, 24-48, and 48-72-hours post-dose
Six Symptom Responses During Ethanol Interactions Assessments (EIAs)
Time Frame: Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169
The degree of aldehyde dehydrogenase 2 (ALDH2) reduction was measured by quantitative assessment of 6 symptom (flushing, headache, palpitations, light-headedness, nausea, and vomiting) responses during EIAs. Each of 6 symptoms was assessed at each of the 4 time points during each EIA. Composite score at each time point was the sum of severity ratings for each of the 6 symptoms. Peak composite score (of the 3 post-alcohol initiation composite scores at each EIA test) was used as the subject's peak score for that EIA test. The point system was as follows: 0 point = symptom not present, 1 point = mild severity of symptom, 2 points = moderate severity of symptom and 3 points = severe severity of symptom. Participants were given a composite score, which was the sum of the scores of all 6 symptoms (highest possible score is 18).
Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169
Cmax: Maximum Observed Plasma Concentration of Acetaldehyde
Time Frame: Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169
Maximum plasma concentration of acetaldehyde was measured to evaluate the pharmacodynamic effects of ALDH2 reduction by DCR-AUD during serial EIAs days.
Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169
AUC0-2.5: Area Under the Concentration Time Curve From Time 0 to Fixed Time 2.5 of Acetaldehyde
Time Frame: Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169
Area under the concentration time curve from time 0 to fixed time 2.5 of acetaldehyde was measured to evaluate the pharmacodynamic effects of ALDH2 reduction by DCR-AUD during serial EIAs days.
Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169
Change From Baseline in Heart Rate
Time Frame: Baseline (Day -1), Day 169
Heart rate is measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIA. Heart rate was monitored by telemetry during the EIAs.
Baseline (Day -1), Day 169
Change From Baseline in Facial Skin Temperature
Time Frame: Baseline (Day -1), Day 169
Change in facial skin temperature was measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIAs for the expanded group. Facial skin temperature was measured using a surface scanning thermometer.
Baseline (Day -1), Day 169
Change From Baseline in Subjective Effects of Alcohol Scale (SEAS) Score
Time Frame: Baseline (Day -1), Day 169
Subjective feelings of alcohol intoxication or intolerance is measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIAs. Participants' subjective experience of the effects of alcohol was assessed using the SEAS. The SEAS is a 14-item tool that allows participants to rate the subjective effects of alcohol. Participants rated the extent to which they were feeling (high/low arousal positive: relaxed, wobbly, lively, secure, woozy, fun, calm, dizzy, mellow, funny, talkative and high/low arousal negative: demanding, rude and aggressive) on an 11-point scale from (0 = not at all, 10 = extremely). higher values represent more effects.
Baseline (Day -1), Day 169

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Parexel

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 21, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 18, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 19, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 25, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DCR-AUD-101
  • U44AA027404 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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