Safety and Tolerability of Pirfenidone in Acute Pancreatitis

NCT05350371 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB-300008875
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of the current pilot clinical trial is to evaluate the safety and tolerability of pirfenidone in patients with predicted moderately severe and severe acute pancreatitis. Pirfenidone is currently approved by FDA for the treatment of idiopathic pulmonary fibrosis. Now, over 5 years of data has accumulated demonstrating safety of its use in humans. The investigators' preclinical data suggest that pirfenidone is very effective in reducing the severity of acute pancreatitis in animal models. Following are the objectives of the proposed clinical trial: Primary Objective:

• To evaluate the safety and tolerability of pirfenidone, compared to placebo, in patients predicted to have moderately severe or severe AP.
• To evaluate the efficacy of pirfenidone in reducing the laboratory markers of inflammation and improving patient reported outcome measures. Secondary Objective: \- To evaluate the efficacy of pirfenidone in reducing the severity of acute pancreatitis, as measured by well-defined endpoints.

Conditions

Pancreatitis, Acute

Outcome Measures

Primary Outcomes (4)

• Development of anticipated or un-anticipated serious adverse events (class 3 or 4)

  Development of anticipated or un-anticipated serious adverse events (class 3 or 4)

  6 months

• percentage of patients starting and completion of the planned drug treatment

  percentage of patients starting and completion of the planned drug treatment

  7 days

• Changes in C-reactive protein (CRP), TNF-α, interleukin (IL)-6, IL-8 and IL-10 levels

  Compared to base line

  7 days

• percentage of patients having decrease in PAN-PROMISE score by at least 10 points at 72h after initiation of the drug

  Measurement of PAN-PROMISE score

  3 days

Secondary Outcomes (5)

• cumulative PAN-PROMISE score

  7

• cumulative PASS score

  duration of admission

• PASS score at the time of discharge

  duration of admission

• Composition outcome

  6 months

• Readmission and/or ER visits

  within 30 days and within 6 months

Study Arms (2)

Placebo

EXPERIMENTAL

Drug: Placebo

Pirfenidone Treatment

EXPERIMENTAL

Drug: Pirfenidone Oral Tablet

Interventions

Pirfenidone Oral Tablet DRUG

Patients in the pirfenidone treatment arm will be given pirfenidone 267mg tablet, tid for 1 day followed by dose escalation to two 267 mg tablet tid for 6 days. Thus, the treatment will be for total of 7 days or till patients develop an adverse event that requires their participation in the study to be stopped.

Pirfenidone Treatment

Placebo DRUG

The placebo tablets will be an exact replica of the pirfenidone tablet.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 - 85 years of age
• Admitted to hospital for AP, defined by at least 2 of the following 3:
• amylase or lipase values, or both, that are greater than 3 times the upper limit of normal values
• characteristic cross-sectional imaging
• typical upper abdominal pain- acute onset of a persistent, severe, epigastric pain often radiating to the back
• Patients identified, approached, and consented to administer study medication or placebo within 48 hours of diagnosis of AP.
• Predicted to have MSAP or SAP by presence of one or more of the following criteria
• APACHE II ≥ 8
• Modified Glasgow or Imrie score ≥ 3
• CRP \> 150 mg/dL
• PASS score \> 140 at or within 48 hrs. of admission
• CT or MRI imaging suggesting pancreatic and/or peri-pancreatic necrosis

You may not qualify if:

• Age \< 18 or \> 85 years
• Body weight \> 200 kg
• Presentation to the medical attention \> 48 h after diagnosis of AP
• Inability to recruit, randomize and start the allocated treatment within 48h of start of pain
• Ongoing AP or diagnosis of AP in previous 30 days
• Chronic pancreatitis
• Known hypersensitivity to pirfenidone
• AST/ALT ≥ 2 times the upper normal limit.
• Alkaline phosphatase ≥ 2 times the upper normal limit
• Bilirubin higher than upper normal limit
• Moderate to severe heart failure and/or coronary heart disease (New York Heart Association (NYHA) Functional Class III/IV)
• On home oxygen or home mechanical ventilation
• Advanced liver disease
• Paralytic ileus or significant nausea and vomiting
• Chronic Diarrhea

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Mayo Clinic: collaborator

Study Sites (2)

UAB

Birmingham, Alabama, 35294, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

WITHDRAWN

Related Publications (2)

• Palathingal Bava E, George J, Tarique M, Iyer S, Sahay P, Gomez Aguilar B, Edwards DB, Giri B, Sethi V, Jain T, Sharma P, Vaish U, C Jacob HK, Ferrantella A, Maynard CL, Saluja AK, Dawra RK, Dudeja V. Pirfenidone increases IL-10 and improves acute pancreatitis in multiple clinically relevant murine models. JCI Insight. 2022 Jan 25;7(2):e141108. doi: 10.1172/jci.insight.141108.

  PMID: 34847076 BACKGROUND

• Bava EP, Jain T, Al-Obaidi M, Evans Z, Doto D, Vege SS, Dudeja V. Safety, tolerability and therapeutic efficacy of anti-inflammatory drug pirfenidone in acute pancreatitis patients: Protocol for a randomized pilot clinical trial. Pancreatology. 2025 Mar;25(2):214-220. doi: 10.1016/j.pan.2025.01.004. Epub 2025 Jan 13.

  PMID: 39864969 DERIVED

MeSH Terms

Conditions

Pancreatitis

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Central Study Contacts

Vikas Dudeja, MD

CONTACT

205 975 7836; vdudeja@uabmc.edu

Mustafa AL-Oabidi, MD

CONTACT

2054139974; malobaidi@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 28, 2022
• Study Start: August 1, 2023
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: August 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)