Using prolonged-release pirfenidone to treat advanced liver fibrosis in hepatitis C patients

Evaluation of Prolonged-release Pirfenidone in Patients With Viral C Hepatitis, With Sustained Viral Response and Advanced Residual Liver Fibrosis. Potential Role of Epigenetics to Understand Therapeutic Changes (MINERVA).

This study is testing if a new form of pirfenidone can help people with advanced liver fibrosis from hepatitis C feel better and improve their liver health over a year.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Guadalajara (Academic / other)
• Locations: 2 sites (Guadalajara, Jalisco and 1 other locations)
• Trial ID: NCT05542615 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of prolonged-release pirfenidone (PR-PFD) on patients with advanced liver fibrosis due to chronic hepatitis C. The study aims to assess the safety and efficacy of two daily doses of pirfenidone over a 12-month period, focusing on its potential to influence epigenetic factors related to liver fibrosis progression. Sixty patients with a history of sustained viral response after antiviral treatment will be monitored for changes in fibrosis levels and gene expression. The trial will adhere to ethical standards and utilize descriptive and analytical statistical methods for data analysis.

Who should consider this trial

Good fit: Ideal candidates are patients with chronic hepatitis C who have achieved a sustained viral response but still exhibit advanced liver fibrosis.

Not a fit: Patients with decompensated liver disease or those who have not responded to antiviral treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve liver health and reduce fibrosis in patients with chronic hepatitis C.

How similar studies have performed: While the use of pirfenidone has shown promise in other conditions, this specific application for liver fibrosis is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Patients with a history of Chronic Viral Hepatitis C, of all genotypes, demonstrated with previous studies (positive viral load).
2. History of treatment with direct acting antivirals (AAD).
3. Demonstration of negative viral load at least 6 months after completing treatment with AAD, considered as sustained viral response (SVR).
4. Fibrotest and / or Liver Elastography test with advanced liver fibrosis scores (F3-F4).
5. Verification of advanced liver fibrosis in a liver biopsy.
6. Patients with Child Pugh functional class A or B and in stable clinical conditions (without active variceal hemorrhage, ascites or refractory encephalopathy) with consumption of drugs at stable doses in at least 30 days.
7. Laboratory tests that confirm her condition and functional class, with results that, in the opinion of the main researcher, do not put the patient at risk:

   * Complete blood count, with hemoglobin values ≥ 10 g / dL, leukocytes ≥ 3,000 mL, platelets ≥ 50,000 mL
   * Creatinine \<1.8 mg / dL

Exclusion Criteria:

1. Child Pugh functional class C (≥ 10 points)
2. Pregnancy and lactation.
3. History of known allergy or hypersensitivity to PFD.
4. Having participated in another clinical study in the 60 days prior to the start of this one.
5. Hospitalization within 30 days prior to the start of administration of the medication.
6. Co-existing liver pathology: alcohol cirrhosis, hemochromatosis, Wilson's disease, α-1-antitrypsin deficiency, amyloidosis, autoimmune hepatitis, and Primary Biliary Cholangitis).
7. Concomitant systemic infection including viral hepatitis B, HIV, as well as respiratory infections, urinary, digestive, cellulite, etc.
8. Serious concomitant conditions such as Heart Failure, Respiratory Failure and Chronic Kidney Failure.
9. Malignant neoplasms including hepatocellular carcinoma. Patients with basal cell carcinoma or those with malignancies with more than 5 years of inactivity may be considered for the study.
10. Decompensated diabetes mellitus (defined as that with fasting blood glucose values greater than 175 mg / dL and / or glycated hemoglobin greater than 8%).
11. Uncontrolled hypertension despite medications (defined as systolic values ≥ 150 and diastolic values ≥ 100 mmHg).
12. Patients with active alcohol intake in the last 6 months.
13. Use of drugs known as concomitant hepatoprotectors (ursodexosicolic acid, s-adenosyl-methionine, silymarin, among others).
14. Patients with treatment of CYP1A2 inhibitor drugs or other CYP isoenzymes such as: fluvoxamine, amiodarone, fluconazole, chloramphenicol, fluoxentine, paroxentine, ciprofloxacin, rifampin or propafenone, or other medicinal products that, in the opinion of the main investigator, may interfere with the study.
15. Any other clinical condition that in the opinion of the main investigator could compromise the safety and well-being of the patient or jeopardize the conduct of the study.

Where this trial is running

Guadalajara, Jalisco and 1 other locations

• Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, UdeG — Guadalajara, Jalisco, Mexico (Active_not_recruiting)
• Hospital Central Militar — Mexico City, Mexico (Recruiting)

Study contacts

• Study coordinator: Juan Armendariz-Borunda, PhD, FAASLD

Conditions Liver Cirrhosis; Hepatitis C, Chronic; Epigenetic Disorder