Study of DCR-AUD in Healthy Volunteers

NCT05021640 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: DCR-AUD-101U44AA027404
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Alcohol Use Disorder (AUD)

Outcome Measures

Primary Outcomes (7)

• 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 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

  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

  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

  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 (12)

• AUC0-last: 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

  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)

  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

  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

  At time interval between 0- 4 hours, 0- 8 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours

Study Arms (5)

Cohort 1: DCRAUD 80 mg

EXPERIMENTAL

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

Drug: DCR-AUD

Cohort 2: DCRAUD 240 mg

PLACEBO COMPARATOR

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

Drug: DCR-AUD

Cohort 3: DCR-AUD 480 mg

EXPERIMENTAL

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

Drug: DCR-AUD

Cohort 4: DCR-AUD 960 mg

PLACEBO COMPARATOR

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

Drug: DCR-AUD

Pooled Placebo

EXPERIMENTAL

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

Drug: Placebo for DCR-AUD

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 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).

Also known as: DCR-A1203

Cohort 1: DCRAUD 80 mg; Cohort 2: DCRAUD 240 mg; Cohort 3: DCR-AUD 480 mg; Cohort 4: DCR-AUD 960 mg

Placebo for DCR-AUD DRUG

0.9% saline for injection

Also known as: Placebo

Pooled 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:

• 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).

You may not qualify if:

• 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

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: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (dept. 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

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, Investigators, site staff, the CRO staff, and the Sponsor Medical Monitor will be blinded to the randomization. Other members of the Sponsor staff will be unblinded for the duration of the study. Complete details will be presented in the Study Blinding Plan.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 25, 2021
• Study Start: September 21, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-12

Locations

US (1)