Efficacy and Safety of Guanabenz for Nonalcoholic Fatty Liver Disease

NCT05084404 | Unknown Phase 2 DMC

• 1 other identifier: YCU-21001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the efficacy and safety of 4 mg/day of WY-8678 (guanabenz acetate) and 8 mg/day of WY-8678 (guanabenz acetate) in patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH patients) with hypertension

Conditions

Nonalcoholic Fatty Liver; Nonalcoholic Steatohepatitis

Keywords

Nonalcoholic Fatty Liver; Nonalcoholic Steatohepatitis; Guanabenz; Phase 2 trial

Outcome Measures

Primary Outcomes (1)

• Percentage of those where the liver fat content (%) measured by MRI-PDFF at 16 weeks decreased by ≥ 3.46% from baseline (%)

  MRI-PDFF

  Week 16

Secondary Outcomes (12)

• Percentage of those where the liver fat content (%) measured by MRI-PDFF at 16 weeks decreased by 3.46% or more from baseline for 4 mg group and 8 mg group (%)

  Week 16

• The absolute change in liver fat content measured by MRI-PDFF

  Week 16

• Rate of change in ALT

  Week 16

• Rate of change in AST

  Week 16

• Rate of change in gamma-glutamyl transferase (γ-GTP)

  Week 16

Study Arms (2)

4 mg/day of WY-8678 (guanabenz acetate)

EXPERIMENTAL

Drug: Experimental: 4 mg/day of WY-8678 (guanabenz acetate)

8 mg/day of WY-8678 (guanabenz acetate)

EXPERIMENTAL

Drug: Experimental: 8 mg/day of WY-8678 (guanabenz acetate)

Interventions

Experimental: 4 mg/day of WY-8678 (guanabenz acetate) DRUG

Patients with nonalcoholic fatty liver disease are administered 4 mg/day of WY-8678 (guanabenz acetate) twice daily for 16 weeks

4 mg/day of WY-8678 (guanabenz acetate)

Experimental: 8 mg/day of WY-8678 (guanabenz acetate) DRUG

Patients with nonalcoholic fatty liver disease are administered 8 mg/day of WY-8678 (guanabenz acetate) twice daily for 16 weeks

8 mg/day of WY-8678 (guanabenz acetate)

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have received a full explanation about this study and who have provided written consent.
• Patients ≥ 20 years of age ≤ 75 years of age at the time consent was provided.
• Patients diagnosed with essential hypertension and whose systolic blood pressure at the time of screening is ≥ 130 mmHg and/or diastolic blood pressure is ≥ 85 mmHg (according to the diagnostic criteria for metabolic syndrome)
• Patients diagnosed with NAFLD/NASH who meet the following criteria (1) or (2) (1) Patients diagnosed with NAFLD who meet the following three criteria: ・Diagnostic imaging or histological evidence of fatty liver, ・Alcohol intake \< 30 g/day for men and \< 20 g/day for women for 12 or more consecutive weeks one year before screening, ・Absence of other factors that cause fattening or chronic liver disease. (2) Patients with a definitive diagnosis of NASH by biopsy within 32 weeks before screening \* The definitive diagnostic criteria for NASH are defined as a fibrosis stage in liver biopsy in the evaluation using the "NASH Clinical Research Network (CRN) criteria" by an F1-F3 pathologist and a NAFLD activity score (NAS) ≥4 points (each item has one or more points): ・Steatosis (0-3 points)
• Ballooning (0-2 points)
• Inflammation in the lobules (0-3 points)
• Patients with magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) liver fat mass ≥ 8% at screening.
• Patients with magnetic resonance elastography (MRE) value ≤ 3.6 kPa at screening.
• Patients with a body mass index (BMI) ≥ 25 kg/m2 at the time of screening.
• Patients receiving diet or exercise therapy 12 weeks before screening, with no improvement.
• Patients who are willing to maintain a stable diet and physical activity during the clinical trial.

You may not qualify if:

• Pregnant, lactating, potentially pregnant women, or patients who do not agree to contraception during the trial period.
• Patients who have taken guanabenz acetate within 16 weeks prior to screening or who have participated in other clinical studies (observational studies are excluded).
• \. Patients with drug allergies to guanabenz acetate. 4. Patients with liver failure or cirrhosis. 5. Patients with the following laboratory test values:
• (1) Alanine aminotransferase (ALT) \> 430 IU/L (males) or \> 240 IU/L (female); or aspartate aminotransferase (AST) \> 300 IU/L (males and females) (2) Prothrombin time-international normalized ratio (PT-INR) ≥ 1.5 (excluding anticoagulant therapy) (3) Total bilirubin value \> 2.0 mg/dL (excluding definitive diagnosis of Gilbert syndrome) (4) Platelet count \< 80,000/μL (5) Estimated glomerular filtration ratio (eGFR) \< 45 (calculated by body surface area correction: standardized eGFR) 6. Patients with a history of acute or chronic liver disease other than NAFLD/NASH and complications:
• Patients suffering from hepatitis B (defined by hepatitis B surface (HBs) antigen positive at the time of screening) or hepatitis C (defined by hepatitis C virus (HCV) antibody positive at the time of screening). However, anti-HCV antibody positive patients who are judged to be negative for hepatitis C virus ribonucleic acid (HCV-RNA) can be registered if they can be confirmed to be negative for at least one year before screening.
• Patients with autoimmune hepatitis.
• Patients with primary biliary cholangitis, primary sclerosing cholangitis, Wilson's disease, α1-antitrypsin deficiency, hemochromatosis or iron overload, drug-induced or alcoholic liver disease, or a history of known biliary atresia.
• Patients with suspicion or definitive diagnosis of hepatocellular carcinoma. 7. Patients with a history of human immunodeficiency virus (HIV) infection. 8. Patients with findings of portal hypertension (complications: ascites, hepatic encephalopathy, varicose veins, splenomegaly).
• \. Patients with a history of NAFLD-related drugs (amiodarone, methotrexate, systemic glucocorticoids, tetracycline, tamoxifen, higher doses of estrogen, anabolic steroids or valproic acid than used for hormone replacement) or other hepatotoxins for at least 4 weeks prior to screening.
• \. Patients who have used the following drugs:
• Patients who used insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, SGLT2 inhibitors, or thiazolidine 12 weeks before screening,
• Patients who used ursodeoxycholic acid or vitamin E 12 weeks before screening,
• Patients whose doses of dyslipidemia drugs or antihypertensive drugs were changed 12 weeks before screening,
• Patients whose dose of oral diabetes treatment drug (dipeptidyl peptidase 4 \[DPP-4\] inhibitor, sulfonylurea \[SU\] preparation, α-glucosidase inhibitor, metformin) was changed 12 weeks before screening,
• Patients who used drugs known to have a significant effect on body weight (including over-the-counter drugs for weight loss) 12 weeks before screening,

Sponsors & Collaborators

• Yokohama City University: lead

Study Sites (1)

Yokohama City University

Yokohama, Kanagawa, 236-0004, Japan

Location

Related Publications (1)

• Iwaki M, Kessoku T, Tanaka K, Ozaki A, Kasai Y, Yamamoto A, Takahashi K, Kobayashi T, Nogami A, Honda Y, Ogawa Y, Imajo K, Yoneda M, Kobayashi N, Saito S, Nakajima A. Efficacy and safety of guanabenz acetate treatment for non-alcoholic fatty liver disease: a study protocol for a randomised investigator-initiated phase IIa study. BMJ Open. 2022 Jul 12;12(7):e060335. doi: 10.1136/bmjopen-2021-060335.

  PMID: 35820743 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Guanabenz

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2021
• First Posted: October 19, 2021
• Study Start: October 29, 2021
• Primary Completion: February 28, 2023
• Study Completion: June 30, 2023
• Last Updated: September 27, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)