Prolonged Release Pirfenidone for Advanced Residual Liver Fibrosis (MINERVA).

NCT05542615 | Unknown Phase 2

• 1 other identifier: MINERVA
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

Prolonged-Release Pirfenidone (PR-PFD) is an anti-fibrogenic and anti-inflammatory molecule used for the treatment of idiopathic pulmonary fibrosis (approved by FDA) and liver fibrosis (approved in Mexico by COFEPRIS). PFD effects are mediated in part through inhibition of TGFβ, TNFα, IL-1 and IL-6, along with NFκB activation down-regulation causing reduced TNFα and IFNγ levels. The aim of this protocol is to know if the epigenetic factors induced by PR-PFD have a regulatory role to understand the progression variants in liver fibrosis in a group of patients with viral hepatitis C, with a history of sustained viral response and advanced residual liver fibrosis. To assess the safety and efficacy of two daily doses of pirfenidone (KitosCell® LP), in patients with compensated liver cirrhosis.

Conditions

Liver Cirrhosis; Hepatitis C, Chronic; Epigenetic Disorder

Outcome Measures

Primary Outcomes (2)

• Liver biopsy

  Reduction of one unit in the METAVIR histological scale (F0-F4)

  12 months

• Elastography

  ≥30% reduction in the final Pascal score, compared to baseline.

  12 months

Secondary Outcomes (4)

• Changes in the degree of methylation

  12 months

• Changes in expression levels of miRNA's

  12 months

• Transcriptome measurement in ccfRNA

  12 months

• Albumin and liver enzyme values

  12 months

Study Arms (1)

Patient

EXPERIMENTAL

Sixty patients with chronic Viral C hepatitis, who have been treated with direct-acting antivirals, with a sustained viral response and who still have advanced fibrosis (F3-F4).

Drug: Prolonged-Release Pirfenidone

Interventions

Prolonged-Release Pirfenidone DRUG

1200 mg / day of Pirfenidone (KitosCell® LP)

Patient

Eligibility Criteria

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

You may qualify if:

• Patients with a history of Chronic Viral Hepatitis C, of all genotypes, demonstrated with previous studies (positive viral load).
• History of treatment with direct acting antivirals (AAD).
• Demonstration of negative viral load at least 6 months after completing treatment with AAD, considered as sustained viral response (SVR).
• Fibrotest and / or Liver Elastography test with advanced liver fibrosis scores (F3-F4).
• Verification of advanced liver fibrosis in a liver biopsy.
• 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.
• 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

You may not qualify if:

• Child Pugh functional class C (≥ 10 points)
• Pregnancy and lactation.
• History of known allergy or hypersensitivity to PFD.
• Having participated in another clinical study in the 60 days prior to the start of this one.
• Hospitalization within 30 days prior to the start of administration of the medication.
• Co-existing liver pathology: alcohol cirrhosis, hemochromatosis, Wilson's disease, α-1-antitrypsin deficiency, amyloidosis, autoimmune hepatitis, and Primary Biliary Cholangitis).
• Concomitant systemic infection including viral hepatitis B, HIV, as well as respiratory infections, urinary, digestive, cellulite, etc.
• Serious concomitant conditions such as Heart Failure, Respiratory Failure and Chronic Kidney Failure.
• 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.
• Decompensated diabetes mellitus (defined as that with fasting blood glucose values greater than 175 mg / dL and / or glycated hemoglobin greater than 8%).
• Uncontrolled hypertension despite medications (defined as systolic values ≥ 150 and diastolic values ≥ 100 mmHg).
• Patients with active alcohol intake in the last 6 months.
• Use of drugs known as concomitant hepatoprotectors (ursodexosicolic acid, s-adenosyl-methionine, silymarin, among others).
• 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.
• 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.

Sponsors & Collaborators

• University of Guadalajara: lead
• Hospital Central Militar: collaborator

Study Sites (2)

Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, UdeG

Guadalajara, Jalisco, 44340, Mexico

ACTIVE NOT RECRUITING

Hospital Central Militar

Mexico City, 11200, Mexico

RECRUITING

Related Publications (1)

• Cerda-Reyes E, de la Rosa-Bibiano R, Sandoval-Rodriguez A, Rosas-Campos R, Torre A, Cornejo-Hernandez S, Escutia-Gutierrez R, Vazquez-Esqueda A, Gutierrez-Cuevas J, Gutierrez-Atemis A, Amezquita-Perez S, Poo JL, Garrido-Sanchez GA, Bastida-Alquicira J, Saldana-Rivera E, Lozano-Trenado LM, Ramon-Aguilar J, Madrigal JA, Armendariz-Borunda J. HCV patients with residual fibrosis after DAA treatment re-establish their epigenetic signature after prolonged-release pirfenidone: MINERVA study. Clin Epigenetics. 2025 Oct 3;17(1):157. doi: 10.1186/s13148-025-01969-y.

  PMID: 41044745 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Hepatitis C, Chronic

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Chronic Disease; Disease Attributes

Central Study Contacts

Juan Armendariz-Borunda, PhD, FAASLD

CONTACT

+52 1058 5200; armdbo@gmail.com

Eira Cerda-Reyes, MD

CONTACT

+52 55 2122 1100; arieirace@yahoo.com.mx

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Institute of Molecular Biology in Medicine

Model Details: This will be a real-life, open-label, proof of concept trial to assess the safety and efficacy of two daily doses of pirfenidone (KitosCell® LP), in patients with compensated liver cirrhosis.

Study Record Dates

• First Submitted: September 13, 2022
• First Posted: September 15, 2022
• Study Start: August 1, 2019
• Primary Completion: December 1, 2023
• Study Completion: January 1, 2024
• Last Updated: July 6, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

ME (2)