Safety and Tolerability of Pirfenidone in Acute Pancreatitis

Pancreatitis, Acute Clinical Trial

Official title:

Evaluation of Pirfenidone as a Therapy in Patients With Predicted Moderate to Severe Acute Pancreatitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05350371
• Other study ID #: IRB-300008875
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 1, 2023
• Est. completion date: July 2025

Study information

• Verified date: August 2023
• Source: University of Alabama at Birmingham
• Contact: Vikas Dudeja, MD
• Phone: 205 975 7836
• Email: vdudeja[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study is a Randomized Pilot clinical trial evaluating safety and tolerability of pirfenidone in patients with predicted moderately severe to severe acute pancreatitis. There are built in secondary end-points for efficacy. The patients with acute pancreatitis, who present within 48h of establishment of the diagnosis, will be screened for exclusion and inclusion criteria and consented for the clinical trial. Patients with be randomized into placebo or pirfenidone arm and followed daily in-person, while in hospital, and by telephone once discharged from the hospital (weekly for 4 weeks, then monthly for up to 6 months) for study end points.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Patients 18 - 85 years of age

2. Admitted to hospital for AP, defined by at least 2 of the following 3:

1. amylase or lipase values, or both, that are greater than 3 times the upper limit of normal values

2. characteristic cross-sectional imaging

3. typical upper abdominal pain- acute onset of a persistent, severe, epigastric pain often radiating to the back

3. Patients identified, approached, and consented to administer study medication or placebo within 48 hours of diagnosis of AP.

4. Predicted to have MSAP or SAP by presence of one or more of the following criteria

1. APACHE II = 8

2. Modified Glasgow or Imrie score = 3

3. CRP > 150 mg/dL

4. PASS score > 140 at or within 48 hrs. of admission

5. CT or MRI imaging suggesting pancreatic and/or peri-pancreatic necrosis

Exclusion Criteria:

1. Age < 18 or > 85 years

2. Body weight > 200 kg

3. Presentation to the medical attention > 48 h after diagnosis of AP

4. Inability to recruit, randomize and start the allocated treatment within 48h of start of pain

5. Ongoing AP or diagnosis of AP in previous 30 days

6. Chronic pancreatitis

7. Known hypersensitivity to pirfenidone

8. AST/ALT = 2 times the upper normal limit.

9. Alkaline phosphatase = 2 times the upper normal limit

10. Bilirubin higher than upper normal limit

11. Moderate to severe heart failure and/or coronary heart disease (New York Heart Association (NYHA) Functional Class III/IV)

12. On home oxygen or home mechanical ventilation

13. Advanced liver disease

14. Paralytic ileus or significant nausea and vomiting

15. Chronic Diarrhea

16. Immunosuppressive disorder or on immunosuppressive medications

17. Active or advanced malignancy

18. Known cancer that is end-stage with ongoing palliative care or for which palliative care is appropriate

19. Known established infection prior to the onset of acute pancreatitis

20. Known history of infective hepatitis

21. Known live vaccines or therapeutic infectious agents within one month of admission

22. Known pregnancy or lactation at the time of admission

23. Ongoing photosensitivity and rash

24. Women of childbearing potential who are not on oral or injectable contraceptives or IUDs and do not consent to practice abstinence for period of 4 weeks.

25. Known to be currently participating in a trial testing any investigational medicinal product or participation in a clinical study involving a medicinal product in the last three months

26. Alcohol or substance abuse in the past 2 years

27. Family or personal history of long QT syndrome ( > 500 msec)

28. Medications like fluvoxamine or sildanefil

29. Significant photosensitivity or new rash

30. Renal disease with GFR < 30

31. Any condition other than above that, in the opinion of the investigator, is likely to result in the death of the patient within the next 2 years

32. Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone

Related Conditions & MeSH terms

• Pancreatitis
• Pancreatitis, Acute

Intervention

Drug:
• Pirfenidone Oral Tablet
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.
• Placebo
The placebo tablets will be an exact replica of the pirfenidone tablet.

Locations

Country	Name	City	State
United States	UAB	Birmingham	Alabama
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	percentage of patients starting and completion of the planned drug treatment	percentage of patients starting and completion of the planned drug treatment	7 days
Primary	Changes in C-reactive protein (CRP), TNF-a, interleukin (IL)-6, IL-8 and IL-10 levels	Compared to base line	7 days
Primary	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	cumulative PAN-PROMISE score	total of the PAN-PROMISE over 7 days	7
Secondary	cumulative PASS score	total of PASS score during admission	duration of admission
Secondary	PASS score at the time of discharge	PASS score measurement	duration of admission
Secondary	Composition outcome	total of development of new or worsening pancreatic or peri-pancreatic necrosis, death or major infection	6 months
Secondary	Readmission and/or ER visits		within 30 days and within 6 months