| Eligibility |
Inclusion Criteria:
1. 21 to 65 years, inclusive, at the time of signing informed consent.
2. Overtly healthy volunteers, as determined by medical evaluation including medical
history, physical examination, and laboratory testing.
3. No diagnosis of AUD within the preceding 12 months per Diagnostic and Statistical
Manual of Mental Disorders (DSM-5).
4. 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.
5. 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).
6. eGFR = 60 mL/min/1.73 m2 at Screening.
7. No history of significant adverse reaction(s) to alcohol. Participant should be
expected to tolerate the amount of alcohol administered during EIAs.
8. Willing to participate in up to 10 EIAs.
9. Has a negative test for SARS-CoV-2 infection on Day -1.
10. 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.
11. 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.
12. BMI within the range 18.0 to 32.0 kg/m2 (inclusive).
13. Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
Exclusion Criteria:
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:
1. Items 1 or 2 of the Suicidal Ideation section, if ideation occurred in the previous 12
months.
2. Items 4 or 5 of the Suicidal Ideation section, in lifetime.
3. 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.
8. 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.
10. 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.
13. Use of prescription medications (except for hormonal replacement/contraceptive
medication for women and inhaled medication for treatment of clinically stable asthma)
within 14 days or 5 half-lives (whichever is longer) prior to administration of study
intervention. Participants being treated for hypothyroid disease must be on stable
treatment (no treatment changes in the preceding 6 months). 14. Receipt of any vaccine
(including COVID-19) within 14 days prior to the first administration of study
intervention. 15. Regular use of OTC medications, including NSAID (periodic or occasional
NSAID use to control temporary pain is not exclusionary). 16. Previously participated in
Dicerna Study DCR-AUD-101. 17. Has received an investigational agent within 30 days or 5
half-lives (whichever is longer) prior to dosing or is in follow-up of another clinical
study prior to initial dosing with the study intervention. 18. Clinically significant
abnormalities in vital signs at Screening: pulse rate (< 40 bpm or > 90 bpm), respiratory
rate, or temperature. 19. Clinically significant abnormalities in 12-lead ECG at Screening
or predose on Day 1, including QTcF > 470 msec in females and > 450 msec in males. 20.
Positive urine drug test at Screening or Day -1. Tests positive for cannabis are not
exclusionary. 21. Seropositive for antibodies to HIV, HBV, or HCV at Screening (historical
testing may be used if performed within the 3 months prior to screening). NOTE: In
participants with previous treatment for hepatitis C with direct-acting HCV medication and
seropositivity for HCV, or in participants with prior infection and spontaneous resolution,
HCV RNA must be undetectable (at least 2 negative HCV RNA tests at least 12 weeks apart),
and the HCV infection must have been resolved or cured > 3 years prior to initial dosing
with the investigational medication. 22. Safety laboratory test result at Screening
considered clinically unacceptable for study participation by the Investigator. 23. History
of intolerance to SC injection(s) or significant abdominal scarring that could potentially
hinder study intervention administration or evaluation of local injection site
tolerability. 24. Scheduled for an elective surgical procedure during the conduct of this
study.
25. 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:
1. 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.
2. Study participants will be advised to avoid consuming more than 4 drinks during any
drinking session outside of in-clinic EIAs.
3. Study participants will be instructed to stop drinking at the onset of any ethanol
reaction symptoms during outside drinking sessions.
4. Tobacco/nicotine use is not restricted.
5. 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.
6. Study participants should abstain from strenuous exercise for 24 hours before each
blood collection for clinical laboratory tests. Participants may participate in light
recreational activities (e.g., walking at a pace < 3 miles per hour, shopping,
watering plants) in that 24-hour time period.
7. For each EIA study visit, participants will be required to fast for at least 3 hours
and then will be fed a standardized meal in the clinic prior to administration of ETOH
for the EIA.
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