Pirfenidone for Recurrent Acute Pancreatitis

(PirfenidoneRAP Trial)

Recruiting at 1 trial location

Overseen By kondal Kyanam, M.B.B.S.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Immunosuppressants, Strong CYP1A2 inhibitors

Disqualifiers: Chronic pancreatitis, Heart failure, Liver disease, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

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: Unknown

Duration: 6 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of pirfenidone, a drug designed to reduce inflammation, for individuals with recurrent acute pancreatitis, a painful condition marked by repeated inflammation of the pancreas. The study will assess the safety and effectiveness of pirfenidone in reducing the frequency and severity of pancreatitis episodes. Participants will receive either the drug or a placebo (a substance with no active treatment) for comparison. Suitable candidates have experienced two or more episodes of acute pancreatitis, with symptoms such as severe upper abdominal pain. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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 does exclude participants on certain medications like strong or moderate CYP1A2 inhibitors and 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 extensively studied pirfenidone to assess its safety and tolerability. In past studies, pirfenidone reduced the severity of sudden pancreas inflammation in animals, suggesting potential benefits for humans without causing serious side effects.

While specific information on its use in humans with recurring pancreas inflammation is limited, pirfenidone is already used for conditions like lung fibrosis, providing some confidence in its safety. People taking pirfenidone for lung issues have generally tolerated it well, with mild to moderate side effects such as nausea or tiredness.

The current study focuses on evaluating the safety and tolerability of pirfenidone for individuals with recurring pancreas inflammation. Although there is some confidence in its safety, more detailed information from human studies is still being gathered. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatitis?

Most treatments for recurrent acute pancreatitis focus on managing symptoms and preventing attacks through lifestyle changes and medications like enzyme supplements and pain relievers. However, Pirfenidone is unique because it targets the underlying inflammation that contributes to pancreatitis. This drug is an anti-fibrotic agent, which means it helps prevent and reduce scarring of the pancreas tissue. Researchers are excited about Pirfenidone because it offers a new approach by addressing the root cause rather than just the symptoms, potentially leading to better long-term outcomes for patients with recurrent acute pancreatitis.

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

This trial will compare Pirfenidone with a placebo to evaluate its effectiveness in treating recurrent acute pancreatitis. Research has shown that Pirfenidone might help treat this condition. In animal studies, Pirfenidone greatly reduced the severity of pancreatitis. These studies suggest that Pirfenidone works by boosting IL-10, a protein that helps control inflammation, which could prevent pancreatitis from worsening. Although most evidence comes from early studies, these findings are promising for its potential use in people. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 who have had recurrent acute pancreatitis, which means they've experienced multiple episodes of this condition. Participants must have been discharged from the hospital and show certain levels of digestive enzymes indicating pancreatitis. They should not be currently hospitalized.

Inclusion Criteria

I am starting a new medication or placebo treatment.

I have mild acute pancreatitis.

I have been discharged from the hospital.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pirfenidone or placebo treatment for 6 months

6 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Periodic visits for outcome measures

What Are the Treatments Tested in This Trial?

Interventions

• Pirfenidone

Trial Overview The study is testing Pirfenidone, a medication that could potentially treat recurrent acute pancreatitis, against a placebo (a substance with no therapeutic effect). The goal is to see if Pirfenidone can safely reduce symptoms and prevent future attacks.

How Is the Trial Designed?

Group I: Pirfenidone Experimental Treatment 1 Intervention

Pirfenidone Days 1-7: 267 mg PO TID (801 mg/day) Days 8-14: 534 mg PO TID (1602 mg/day) Day 15 and thereafter: 801 mg PO TID; not to exceed 2403 mg/day Total duration of experimental or placebo drug treatment 6 months

Group II: Placebo Placebo Group 1 Intervention

Placebo

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+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Published Research Related to This Trial

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]

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]

Extensive safety testing of GLP-1-based therapies, including exenatide and saxagliptin, involving over 70 non-clinical toxicology studies, showed no drug-related pancreatic damage or neoplasia in animals, even at doses significantly higher than those used in humans.

The findings from more than 2400 pancreata assessed indicate that GLP-1 therapies do not pose a risk of pancreatic injury, supporting their safety for use in treating conditions like diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The glucagon-like peptide-1-based therapeutics exenatide and saxagliptin did not cause detrimental effects on the pancreas in mice, rats, dogs and monkeys. Roy, D., Chadwick, KD., Tatarkiewicz, K., et al.[2018]

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]

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]

A 54-year-old man developed recurrent acute pancreatitis after starting lisinopril, indicating a potential link between this ACE inhibitor and the condition.

After stopping lisinopril and switching to amlodipine, the patient showed significant improvement and did not experience further episodes of pancreatitis over the next 7 months, suggesting that discontinuation of lisinopril may be an effective intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent acute pancreatitis probably secondary to lisinopril. Kanbay, M., Selcuk, H., Yilmaz, U., et al.[2013]

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]

Recurrent acute pancreatitis can lead to chronic pancreatitis and significantly affects patients' quality of life, highlighting the need for effective management strategies.

The development of a stepwise algorithm for identifying and eliminating causes of recurrent acute pancreatitis is essential, and future improvements in treatment will rely on better imaging techniques, clinical trials, and understanding the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent acute pancreatitis: an algorithmic approach to identification and elimination of inciting factors. Somogyi, L., Martin, SP., Venkatesan, T., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1424390325000043

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.

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

Pirfenidone increases IL-10 and improves acute ... Our studies demonstrate that pirfenidone is effective in abrogating the progression of moderate to severe AP in preclinical models. We delineate its mechanism ...

5. grantome.com grantome.com/grant/NIH/R01-DK111834-02

Therapeutic efficacy of Pirfenidone in Pancreatitis In multiple acute and chronic inflammatory diseases, Tregs have been shown to attenuate inflammation, improve disease severity and help in recovery. Based on ...

6. 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.

7. 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.