Prolonged Release Pirfenidone Versus Placebo in Compensated Cirrhosis.

NCT06267794 | Completed Phase 2

• 1 other identifier: ODISEA Study
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

This will be a multicenter, double-blind clinical trial to evaluate the safety and efficacy of two doses of prolonged release pirfenidone, compared against placebo plus conventional therapy in patients with compensated liver cirrhosis. The study will be conducted in compliance with International Standard good clinical practices (GCPs) and the Declaration of Helsinki. The protocol is approved by a local Institutional Review Board and registered in clinical trials.gov.

Conditions

Liver Fibrosis; Cirrhosis, Liver; Chronic Liver Disease

Keywords

Liver fibrosis; Fibrosis treatment; Fibrosis reversibility; Pirfenidone; Prolonged release pirfenidone

Outcome Measures

Primary Outcomes (2)

• Change in liver fibrosis

  Fibrosis change based on Hepatic Elastography. Variation of fibrosis score by at least 30% in kilo Pascals (kPa) according to accurate hepatic elastography measurements. Fibrosis change based on Fibrotest. Change of fibrosis score by at least 10% in Fibrotest units.

  6, 12, 18 and 24 months

• Clinical side effects

  Clinical side effects will be evaluated according to World Health Organization guidelines. The following definitions will be used to grade the severity of adverse events: Mild: Awareness of sign, symptom or event, but easily tolerated. Moderate: Discomfort sufficient to cause interference with usual activity and may require intervention. Serious: Disabling without ability to do usual activities, or significantly affects clinical status and requires intervention. Puts Life at Risk: Immediate risk of death (Sponsor must be notified within 24 hours). The Investigators must also evaluate the relationship of any adverse event with the use of the study drug, based on the available information, according to the following guidelines: 0 = Unrelated 1. = Possibly related 2. = Probably related

  6, 12, 18 and 24 months

Secondary Outcomes (8)

• Improvement in Child Pugh score

  6, 12, 18 and 24 months

• Improvement in MELD score

  6, 12, 18 and 24 months

• Improvement in bilirrubin and albumin

  6, 12, 18 and 24 months

• Improvement in prothrombin time

  6, 12, 18 and 24 months

• Improvement in liver enzymes

  6, 12, 18 and 24 months

Study Arms (3)

Prolonged release pirfenidone (PR-PFD), 1200 mg group

EXPERIMENTAL

Subjects will receive one tablet during breakfast and 2 tablets during dinner.

Drug: Pirfenidone 1200 mg

PR-PFD, 1800 mg group

ACTIVE COMPARATOR

Subjects will receive one tablet during breakfast and 2 tablets during dinner.

Drug: Pirfenidone 1800 mg

Placebo group

PLACEBO COMPARATOR

Subjects will receive one tablet during breakfast and 2 tablets during dinner.

Drug: Placebo

Interventions

Pirfenidone 1200 mg DRUG

1200 mg dosage. Additionally, all participating subjects will receive standard treatment care for patients with cirrhosis.

Also known as: Prolonged-release pirfenidone

Prolonged release pirfenidone (PR-PFD), 1200 mg group

Pirfenidone 1800 mg DRUG

1800 mg dosage. Additionally, all participating subjects will receive standard treatment care for patients with cirrhosis.

Also known as: Prolonged-release pirfenidone

PR-PFD, 1800 mg group

Placebo DRUG

0 mg dosage. Additionally, all participating subjects will receive standard treatment care for patients with cirrhosis.

Placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both genders over 18 years of age.
• Patients with clinical, biochemical, radiological diagnostic confirmation as well as evidence of grade 4 fibrosis based on an invasive (liver biopsy) or non-invasive method (fibrotest and/or fibroscan).
• With functional class A (score of 5 and 6) and B (score of 7 or 8) on the Child-Pugh scale.
• Optionally, transjugular liver biopsy with measurement of the portal system flow pressure gradient, in at least 20% of the population.
• Be controlled with medications that are consumed at stable doses for at least 30 days.
• Have a BMI greater than 19.1 kg/m 2 and less than 34.9 kg/m 2
• Have the required standardized and homogeneous diet for patients
• Do not drink alcoholic beverages for at least one year prior to the start of the study.
• Electrocardiogram normal or without clinical significance.
• Laboratory tests that confirm your condition and functional class, with results that, in the opinion of the principal investigator, do not put the patient at risk:
• Complete blood count, with hemoglobin values ≥ 12 g/dL, leukocytes ≥ 3,500 mL, platelets ≥ 50,000 mL
• Blood chemistry (glucose, urea, creatinine, uric acid, cystatin C).
• Complete liver function tests (total protein, globulin, albumin, ALT, AST, gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), lactic dehydrogenase (LDH), Total Bilirubin, C-reactive Protein).
• Fibrotest and/or FibroScan with a result of F4.
• General urine examination.

You may not qualify if:

• Pregnancy and breastfeeding.
• History of known allergy or hypersensitivity to PFD.
• Have liver cirrhosis with functional reserve B (score of 9) or functional reserve C (score of 10 or more) on the Child-Pugh scale. 11 (See annexes).
• History of Upper Gastrointestinal Bleeding, Ascites, Hepatic Encephalopathy or any other complication due to previous Portal Hypertension.
• Body Mass Index less than 19 kg/m 2 or greater than 35 kg/m 2
• Hemoglobin values less than 12 g/dL.
• Have 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 medication administration.
• Concomitant systemic infection other than hepatitis C virus (HCV), including Respiratory Tract Infections , Urinary Tract Infections, human immunodeficiency virus (HIV), cellulitis, etc.
• Current use (less than 1 month) of colchicine, ursodeoxycholic acid, silimarin, or s-adenosine methionine, or cytotoxic agent, cytokine modulator or receptor antagonist, daily sildenafil or fluvoxamine, theophylline or other methylxanthines, or alternative medicine.
• Have clinical data of pulmonary fibrosis, heart, respiratory or kidney failure (serum creatinine \> 1.5 mg/dL).
• Other medications that, in the opinion of the principal investigator, may interfere with the study.
• Any other clinical condition that causes fibrosis other than liver fibrosis or a condition that, in the opinion of the principal investigator, could compromise the safety and well-being of the patient or put the conduct of the study at risk, such as hepatocellular carcinoma.
• Elimination criteria
• Any patient who presents a clinical finding compatible with decompensated cirrhosis (bleeding of variceal origin, clinical ascites, evident hepatic encephalopathy, hepatocellular carcinoma) or an adverse event or condition that, in the opinion of the principal investigator, warrants suspension of the patient's participation will be suspended from the study, but their data will be considered in the "intention to treat" analysis, when applicable.

Sponsors & Collaborators

• Jorge L Poo: lead

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Placebo will be identical to medication. Methods to assign treatment: Before assigning numbers to subjects, the researcher must confirm that the inclusion criteria have been met, that none of the exclusion criteria apply, that written and signed informed consent has been obtained, that the evaluations of the scrutiny (of admission) and that the required laboratory results are available and meet the admission criteria. To do this, the centers will be assisted with a check list format that contains all the selection criteria. The person responsible for the medication at the research site will contact the Randomization center, where the treatment will be assigned to the patient.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PROMHEPA administrator and Co-Investigator

Model Details: Double blind, placebo-controlled multicenter study

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: February 20, 2024
• Study Start: June 26, 2015
• Primary Completion: December 30, 2021
• Study Completion: March 24, 2023
• Last Updated: February 20, 2024

Record last verified: 2024-02