Safety, Tolerability, and Bioeffects of Alirocumab in Non-treatment Seeking Heavy Drinkers

NCT04781322 | Recruiting Phase 1 FDA Drug FDA Device

• 2 other identifiers: 10000036000036-AA
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Drinking alcohol can lead to swelling and injury in the liver. Long-term heavy drinking may lead to liver disease. Researchers want to study the relationship between a drug called alirocumab, alcohol use, and liver functioning/swelling. Objective: To study the effects of alirocumab in people who drink alcohol. Eligibility: Healthy adults ages 21 to 65 who regularly consume an average of 20 or more drinks per week. Design: Participants will be screened under protocol 14-AA-0181. Participants will get alirocumab or a placebo as an injection under the skin. Participants will give blood and urine samples. They will have physical exams. Participants will have FibroScans . It measures liver and spleen stiffness. Participants will lie on a table. They will expose the lower right and left side of their chest. The machine will send a small vibration to the liver. Participants may have magnetic resonance imaging (MRI) scans of the liver. The MRI scanner is shaped like a cylinder. Participants will lie on a table that slides in and out of the scanner. A device called a coil will be placed over their liver. Participants will have a Doppler scan and ultrasound. These tests measure blood flow in the body. Participants will have an electrocardiogram. It measures heart function. Participants will fill out surveys about how they are feeling, their alcohol consumption, and other behaviors. They will complete cognitive tasks on a computer. Participants will meet with a clinician. They will discuss the participant s assessment results, patterns of drinking, and possibly stopping or cutting down on drinking. Participation will last for 8 weeks. Participants will have 9 study visits.

Conditions

Alcohol Associated Liver Disease; Heavy Drinking Behavior

Keywords

Alcohol; Liver; PCSK9; Fatty Liver; Inflammation

Outcome Measures

Primary Outcomes (1)

• The primary objective is to assess the safety and tolerability of alirocumab in subjects who are heavy drinkers.

  The primary endpoint in the study is to assess the incidence and severity of treatment-emergent adverse events in non-treatment seeking heavy drinkers treated with alirocumab or placebo.

  8 weeks

Secondary Outcomes (1)

• Secondary/exploratory objectives are to assess various biomarkers related to alcohol-induced liver damage and inflammation.

  ongoing

Study Arms (2)

Intervention

EXPERIMENTAL

Heavy drinking healthy volunteers

Drug: Alirocumab

Placebo

PLACEBO COMPARATOR

Heavy drinking healthy volunteers

Other: Placebo

Interventions

Alirocumab DRUG

Alirocumab is a human monoclonal antibody (IgG1) that binds to and inhibits PCSK9 and was approved by the FDA in July of 2015. PCSK9 binds to and promotes degradation of low-density lipoprotein receptors (LDLR) on hepatocyte membranes.

Intervention

Placebo OTHER

Heavy drinking healthy volunteers

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 or female between the age of 21 and 65 years.
• Ability to provide written informed consent.
• Females: Negative urine pregnancy test, not currently breastfeeding, agree to abstain or use accepted form of contraception including use of oral contraceptives; use of barrier method of contraceptive, such as condoms; use of an approved IUD or other long-acting reversible contraceptive (LARC); have a male sexual partner who is surgically sterilized; or have exclusively female sexual partner(s).
• Males: Agree to abstain or use accepted form of contraception, such as condoms.
• Current chronic alcohol use, non-treatment seeking heavy drinker (an average of \>= 20 standard drinks per week for at least 12 weeks).

You may not qualify if:

• Treatment seeking for alcohol use disorder.
• History of a serious hypersensitivity reaction to PCSK9 inhibitors, monoclonal antibodies, or any component of the drug product.
• Chronic use of statins within eight weeks of the study to treat hypercholesteremia, or fibrates, with the exception of fenofibrates, within six weeks of the study.
• Current/past use of PCSK9 inhibitors.
• Clinically significant and/or unstable cardiovascular-disease over the past 12 months.
• Current or prior history of any clinically significant disease, including, fibromyalgia, severe neuropathic pain, seizure disorder, uncontrolled endocrine disease known to influence serum lipids or lipoproteins, hemorrhagic stroke, cancer within the past 5 years (except for adequately treated basal skin cancer, squamous cell skin cancer, or in situ cervical cancer), uncontrolled (defined as Hgb A1c \>8%) or newly diagnosed (within 3 months prior to screening) diabetes, or any other significant abnormality identified at the time of screening that, in the judgment of the investigator or study clinician, would preclude safe completion of the study.
• Positive HIV test or positive Hepatitis B surface antigen (HBsAg), and/or positive Hepatitis C antibody (HCV) at screening.
• Alanine aminotransferase or aspartate aminotransferase exceeding 5 times the upper limit of normal levels at screening will be excluded. Bilirubin 2x UNL or Creatinine \> 1.5 mg/dl at screening will be excluded.
• Triglycerides \> 400mg/dL (\>4.52 mmol/L) at screening.
• Chronic renal failure as estimated by glomerular filtration rate (GFR) \< 60mL/min/1.73 m\^2 at screening.
• Any underlying clinically significant and/or unstable acute or chronic liver disease unrelated to alcohol use at screening.
• Patients with coagulopathy defined as INR \>1.5, prothrombin time prolonged by \> 3s, and/or platelets \<75,000 / mm\^3 at screening.
• Use of any medications that interfere with blood clotting.
• Patients with significant hematologic abnormalities.
• Significant obesity (Obesity Class III) defined as BMI greater than or equal to 40 at screening.

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Fatty Liver; Inflammation

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Falk W Lohoff, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nada M Saleh

CONTACT

(301) 496-3799; nada.saleh@nih.gov

Falk W Lohoff, M.D.

CONTACT

(301) 827-1542; falk.lohoff@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 4, 2021
• Study Start: October 19, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04-24

Locations

US (1)