Aramchol for HIV-associated Nonalcoholic Fatty Liver Disease and Lipodystrophy

NCT02684591 | Completed Phase 2 Results

• 1 other identifier: ARRIVE
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

A subset of patients with NAFLD that have not been extensively studied are those infected with human immunodeficiency virus (HIV). Currently, there is no FDA approved treatment for NAFLD or NASH. Additionally, there have been no significant clinical trials for HIV patients with NAFLD and there are no approved treatment options. We plan to conduct a randomized, double-blinded, placebo-controlled clinical trial to examine the efficacy of 600 mg of Aramchol daily (including 200 mg tablet and 400 mg tablet) versus identical placebo given over 12 weeks to improve HIV-associated hepatic steatosis as measured by a validated and accurate magnetic resonance imaging (MRI)-based technique.

Conditions

Nonalcoholic Fatty Liver Disease; HIV

Outcome Measures

Primary Outcomes (1)

• Efficacy of Aramchol 600 mg vs. Placebo in Improving Hepatic Steatosis Assessed by Magnetic Resonance Imaging in Patients With HIV-associated NAFLD

  To examine the efficacy of aramchol at 600 mg orally daily versus placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with HIV-associated NAFLD

  12 weeks

Secondary Outcomes (1)

• Serum Alanine Aminotransferase (ALT)

  12 Weeks

Study Arms (2)

Aramchol 600 mg orally daily

EXPERIMENTAL

Total 600 mg Aramchol (200 mg/tablet and 400 mg/tablet) per day once a day orally for 12 weeks. Intervention: Aramchol

Drug: Aramchol

Placebo

PLACEBO COMPARATOR

Placebo in the form of a tablet; Two bottles will be given to patient and they will take two pills, once a day orally for 12 weeks.

Drug: Placebo

Interventions

Aramchol DRUG

Aramchol, a conjugate of Cholic acid and Arachidic acid, is a first in class member of a novel family of synthetic Fatty-Acid / Bile-Acid Conjugates (FABACs). FABACs are composed of endogenic compounds, orally administrated with potentially good safety and tolerability parameters

Also known as: arachidyl amido cholanoic acid

Aramchol 600 mg orally daily

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age at entry at least 18 years.
• And at least one of the following risk factor for more severe liver disease: Hypertriglyceridemia based upon ATP-III guidelines, Increased LDL cholesterol or increased total cholesterol based upon ATP-III guidelines, Decreased HDL cholesterol based upon ATP-III guidelines, Serum alanine (ALT) or aspartate (AST) aminotransferase activities that are above the upper limits of normal. 19 or more in women and 30 or more in men, Overweight as defined as BMI: 25 \< 30 kg/m2, Obesity as defined BMI ≥ 30 kg/m2, Hyperuricemia based upon ATP-III guidelines, Prediabetes or Diabetes by American Diabetes Association Criteria
• Lipodystrophy will be confirmed on both clinical and radiologic assessment and defined as: Clinical history and/or exam by the study physician with signs of either facial,temporal, upper or lower extremity lipo-atrophy, Documented abdominal fat accumulation with presence of hepatic steatosis on MRI
• An MRI-determined fat fraction classification threshold (≥5%) will be used to confirm subjects. MR examinations will include four research sequences (three imaging sequences and one single-voxel spectroscopy sequence) that have been developed and refined by Dr. Sirlin, allowing for the measurement of liver fat fraction and newer candidate MR biomarkers for future NAFLD studies. MR examinations will last 20-30 minutes and will be performed without contrast agents. Subjects will be scanned at 1.5T. To assess sequence repeatability, two sequences per subject, block randomized, will be run three times. For MR elastography, MR imaging will be done which will include placing a vibrating paddle over the abdomen while images are obtained. A comprehensive screening questionnaire will be utilized prior to subjects having an MRI. Experienced research MR technologists will perform MR examinations under the supervision of Dr. Sirlin.
• History of HIV documented by a previously positive HIV Elisa or PCR.
• Written informed consent.

You may not qualify if:

• Evidence of another form of liver disease: Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg), Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum, Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy, Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with rimary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis, Wilsons disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilsons disease Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D, Drug-induced liver disease as defined on the basis of typical exposure and history,Bile duct obstruction as shown by imaging studies.
• Evidence of liver cirrhosis based upon clinical assessment, imaging or any of the following lab abnormalities: INR \>1.4, albumin \<3.2 g/dL, platelet count \<90 x 103/microliter
• History of excess alcohol ingestion, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day or 7 drinks per week) in the previous one year.
• Contraindications to MRI: The subject has any contraindication to MR imaging, such as patients with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field, the subject has a history of extreme claustrophobia, The subject cannot fit inside the MR scanner cavity, decompensated liver disease, Child-Pugh score greater than or equal to 7 points
• \. History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months. 7. Recent use (within the last 90 days) of medications to treat hepatic steatosis such as pioglitazone (or medications in the same class) or vitamin E. 8. Use of Aramchol or agents in the same class. 9. Recent use (within the last 90 days) of insulin as an outpatient for management of diabetes.
• \. HbA1c \> 9 or uncontrolled diabetes. 11. Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator would preclude treatment with Aramchol and adequate follow up.
• \. Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year. 13. Pregnancy or inability to practice adequate contraception in women of childbearing potential.
• \. Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study that is suggestive of liver cancer.
• \. Symptoms of uncontrolled gastrointestinal disorders involving motility, gastric acid or gastric emptying malabsorption ,Disorders including but not limited to peptic ulcer disease, gastroesophageal reflux, dyspepsia, gastroparesis, chronic diarrhea, chromic constipation, gall bladder disease,pancreatitis, lactose intolerance and celiac disease.Patients who have used anticholinergic or other drugs known to affect gastrointestinal motility within 7 days prior to dosing and throughout the study will also be excluded
• \. Patients with hypersensitivity to Aramchol or to any of the excipients in the tablets or with hypersensitivity to cholic acid or bile acid sequestrants
• \. Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibility hinder completion of the study.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

San Diego, California, 92103, United States

Location

Related Publications (1)

• Ajmera VH, Cachay E, Ramers C, Vodkin I, Bassirian S, Singh S, Mangla N, Bettencourt R, Aldous JL, Park D, Lee D, Blanchard J, Mamidipalli A, Boehringer A, Aslam S, Leinhard OD, Richards L, Sirlin C, Loomba R. MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial). Hepatology. 2019 Nov;70(5):1531-1545. doi: 10.1002/hep.30674. Epub 2019 Jun 18.

  PMID: 31013363 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

aramchol

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Rohit Loomba, MD, MHSc
• Organization: UCSD

roloomba@ucsd.edu

858-246-2201

Study Officials

• Rohit Loomba, M.D.

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: February 18, 2016
• Study Start: January 1, 2016
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: July 17, 2020
• Results First Posted: August 21, 2019

Record last verified: 2020-07

Locations

US (1)