Pirfenidone for Acute Pancreatitis

Overseen By Mustafa AL-Oabidi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Fluvoxamine, Sildenafil

Disqualifiers: Chronic pancreatitis, Heart failure, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 7 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called pirfenidone to determine its safety and effectiveness for severe acute pancreatitis, a sudden and intense inflammation of the pancreas. Already used for lung issues, pirfenidone has shown promise in animal studies for reducing pancreatitis symptoms. Participants will receive either pirfenidone or a placebo (a non-active substance) to compare results. Individuals hospitalized for acute pancreatitis and experiencing severe upper abdominal pain might be suitable candidates. As a Phase 1, Phase 2 trial, this research aims to understand how pirfenidone works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on immunosuppressive medications and certain drugs like fluvoxamine or sildenafil. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that pirfenidone is likely to be safe for humans?

Research has shown that pirfenidone has been safely used in people for over five years, primarily to treat idiopathic pulmonary fibrosis, a lung condition. The FDA has approved this medication, indicating it has passed several safety checks for that condition. Although pirfenidone is not yet approved for treating sudden inflammation of the pancreas (acute pancreatitis), early studies have shown promising results.

In animal studies, pirfenidone reduced the severity of acute pancreatitis by increasing IL-10, a protein that helps reduce inflammation.

Regarding side effects, no major issues have been reported when pirfenidone is used for other conditions, suggesting it is generally well-tolerated. As with any clinical trial, researchers will closely monitor participants to ensure everyone's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pirfenidone is unique because it offers a new approach to treating acute pancreatitis by targeting inflammation directly. Unlike current treatments, which mainly focus on managing symptoms like pain and dehydration, Pirfenidone works by inhibiting the production of certain molecules that cause inflammation. This mechanism could potentially reduce the severity of the disease more effectively and quickly. Researchers are excited because this could mean faster recovery times and better outcomes for patients suffering from acute pancreatitis.

What evidence suggests that pirfenidone might be an effective treatment for acute pancreatitis?

Research has shown that pirfenidone might reduce the severity of acute pancreatitis. Before testing new treatments on people, scientists conduct preclinical studies in labs. These studies have suggested that pirfenidone can effectively reduce inflammation in animals by increasing IL-10, a substance that helps control inflammation. Pirfenidone is already approved for treating idiopathic pulmonary fibrosis, demonstrating a strong safety record in humans. Although limited information exists from human studies on acute pancreatitis, these early results are promising and suggest that pirfenidone could be helpful for this condition. Participants in this trial will receive either pirfenidone or a placebo to evaluate its effectiveness in treating acute pancreatitis. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-85 with moderately severe to severe acute pancreatitis can join this trial. They must be hospitalized and diagnosed within 48 hours, without certain conditions like liver disease, heart failure, or a recent history of alcohol abuse. Pregnant women and those on specific medications are excluded.

Inclusion Criteria

My pancreatitis is severe, based on tests and scans done within 48 hours of my hospital admission.

I was hospitalized for severe upper stomach pain and my tests show high enzyme levels or imaging confirmed pancreatitis.

I agreed to start the study treatment within 2 days of being diagnosed with AP.

Exclusion Criteria

Women of childbearing potential not on contraceptives or IUDs and not consenting to abstinence for 4 weeks

I have had acute pancreatitis in the last 30 days or it is ongoing.

I sought medical help more than 48 hours after being diagnosed with acute pancreatitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 days

1 visit (in-person)

Treatment

Participants receive pirfenidone or placebo for 7 days to evaluate safety and tolerability

7 days

Daily visits (in-person) while in hospital

Follow-up

Participants are monitored for safety and effectiveness after treatment, with weekly phone follow-ups for 4 weeks and monthly for up to 6 months

6 months

Weekly phone follow-ups for 4 weeks, then monthly for up to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pirfenidone

Trial Overview The trial is testing the safety and effectiveness of Pirfenidone—an FDA-approved drug for lung fibrosis—against a placebo in reducing inflammation in acute pancreatitis patients. Participants will report their outcomes as part of the study.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

Group II: Pirfenidone Treatment Experimental Treatment 1 Intervention

Pirfenidone is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Esbriet for:

• Idiopathic Pulmonary Fibrosis

Approved in United States as Esbriet for:

• Idiopathic Pulmonary Fibrosis

Approved in Canada as Esbriet for:

• Idiopathic Pulmonary Fibrosis

Approved in Japan as Pirespa for:

• Idiopathic Pulmonary Fibrosis

Approved in China as Etuary for:

• Idiopathic Pulmonary Fibrosis

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a study involving liraglutide users followed for a median of 15 months, the incidence rate of acute pancreatitis was slightly higher (187.5 cases per 100,000 person-years) compared to other non-GLP-1 therapies, but this difference was not statistically significant (adjusted RR 1.10).

For pancreatic cancer, liraglutide showed a lower incidence rate (19.9 cases per 100,000 person-years) compared to non-GLP-1 therapies (33.0 cases), suggesting no increased risk associated with liraglutide (adjusted RR 0.65).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, claims-based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs. Funch, D., Gydesen, H., Tornøe, K., et al.[2021]

Pirfenidone, an FDA-approved drug for Idiopathic Pulmonary Fibrosis, has shown promising results in mouse models of chronic pancreatitis (CP) by reducing fibrosis, inflammation, and pancreatic damage, indicating its potential as a new treatment option for CP.

The drug's efficacy appears to be linked to its ability to reduce macrophage infiltration and alter cytokine levels in the pancreas, suggesting that targeting macrophages may be a key mechanism in its therapeutic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirfenidone ameliorates chronic pancreatitis in mouse models through immune and cytokine modulation. Palathingal Bava, E., George, J., Iyer, S., et al.[2022]

Captopril, an angiotensin-converting enzyme inhibitor, significantly reduced serum amylase levels, myeloperoxidase activity, and histopathological damage in rats with acute edematous pancreatitis, indicating its potential as a therapeutic option.

In severe necrotizing pancreatitis, captopril also improved pancreatic tissue damage, while losartan showed some benefits in reducing necrosis and inflammation, but L-158809 did not demonstrate similar protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: a new therapeutic target? Oruc, N., Ozutemiz, O., Nart, D., et al.[2022]

Pirfenidone, an FDA-approved drug for idiopathic pulmonary fibrosis, shows promise in reducing the severity of acute pancreatitis (AP) by decreasing local and systemic injury and inflammation, even when administered at the peak of injury.

The drug works by increasing IL-10 secretion from macrophages and modulating the immune response, as confirmed by experiments that demonstrated its efficacy relies on the presence of IL-10 and macrophages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirfenidone increases IL-10 and improves acute pancreatitis in multiple clinically relevant murine models. Palathingal Bava, E., George, J., Tarique, M., et al.[2022]

In a study of 15 adult patients with pancreas sufficient cystic fibrosis (PS-CF) and a history of acute pancreatitis (AP), the use of CFTR modulators significantly reduced the risk of recurrent AP over an average follow-up of 36.7 months.

None of the patients who continued on CFTR modulators experienced further episodes of AP or required hospitalization for AP-related issues, suggesting that enhancing CFTR function may help protect against pancreatitis in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cystic fibrosis transmembrane conductance regulator modulators reduce the risk of recurrent acute pancreatitis among adult patients with pancreas sufficient cystic fibrosis. Akshintala, VS., Kamal, A., Faghih, M., et al.[2020]

New drugs like somatostatin, octreotide, and loxiglumide have been tested to reduce pancreatic secretion in severe acute pancreatitis, but the mortality rate remains high despite these efforts.

The anti-inflammatory agent IS-741 has shown promise in experimental models of pancreatitis, indicating potential for future clinical applications in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New aspects of pharmaco-therapy for acute pancreatitis]. Takase, K., Ueda, T., Kuroda, Y.[2017]

Data from the FDA Adverse Event Reporting System suggest that incretin-based therapies, like GLP-1 receptor agonists and DPP-4 inhibitors, may increase the risk of acute pancreatitis and pancreatic cancer.

However, population-based observational studies do not support these findings, indicating that current evidence is conflicting and insufficient to determine the true risk associated with these diabetes treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incretin-mimetic therapies and pancreatic disease: a review of observational data. Suarez, EA., Koro, CE., Christian, JB., et al.[2022]

Acute pancreatitis in rats leads to increased pulmonary vascular permeability, indicating that lung injury is a significant complication of this condition.

The administration of lexipafant (BB-882), a platelet-activating factor antagonist, significantly reduced lung injury in the pancreatitis model, suggesting its potential as a therapeutic option for managing complications associated with acute pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung injury in the microembolic model of acute pancreatitis and amelioration by lexipafant (BB-882), a platelet-activating factor antagonist. Galloway, SW., Kingsnorth, AN.[2019]

In a randomized controlled trial involving 83 patients with acute pancreatitis, pentoxifylline did not show any significant benefit over placebo in reducing severe outcomes such as death or organ failure.

Patients receiving pentoxifylline experienced longer hospital stays and higher readmission rates compared to those on placebo, suggesting that pentoxifylline may not be an effective treatment for acute pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis: Challenges and opportunities. Vege, SS., Horibe, M., Chari, ST., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8855813/

Pirfenidone increases IL-10 and improves acute ... Our study also suggests that most of the effects of pirfenidone are mediated through increased secretion of antiinflammatory cytokine IL-10 from macrophages.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05350371

Safety and Tolerability of Pirfenidone in Acute Pancreatitis The investigators' preclinical data suggest that pirfenidone is very effective in reducing the severity of acute pancreatitis in animal models. Following are ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20550241

Safety and Tolerability of Pirfenidone in Acute Pancreatitis The investigators' preclinical data suggest that pirfenidone is very effective in reducing the severity of acute pancreatitis in animal models.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39864969/

Protocol for a randomized pilot clinical trial Based on our preclinical findings, we decided to conduct a pilot trial to evaluate the safety, tolerability and efficacy of pirfenidone in patients with AP.

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/486495

Safety and Tolerability of Pirfenidone in Acute Pancreatitis The investigators' preclinical data suggest that pirfenidone is very effective in reducing the severity of acute pancreatitis in animal models. Following ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06253117/evaluation-of-pirfenidone-as-a-novel-therapeutic-strategy-against-recurrent-acute-pancreatitis

Evaluation of Pirfenidone as a Novel Therapeutic Strategy ... This clinical will evaluate the safety, tolerability and early efficacy of pirenidone in patients with recurrent acute pancreatitis.

7. esbriethcp.com esbriethcp.com/efficacy/clinical-trial-results.html

Clinical Trial Results for IPF | Esbriet® (pirfenidone) Esbriet (pirfenidone) achieved a numerical difference in all-cause mortality in three phase 3 trials. No statistically significant difference over the study ...