Pancreatic Enzyme Replacement Therapy for Pancreatic Insufficiency

(PERT-AP Trial)

Recruiting at 4 trial locations

Overseen By Zoe Krebs, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ohio State University

Must not be taking: PERT

Disqualifiers: Chronic pancreatitis, Pancreas malignancy, Enteropathies, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 26 weeks

60 Participants Needed

Trial Summary

Do I need to stop taking my current medications for this trial?

You must stop taking any pancreatic enzyme replacement therapy (PERT) for 7 days before the baseline visit. The protocol does not specify if you need to stop other medications, so it's best to discuss with the study team.

What data supports the effectiveness of the drug Pancrelipase for pancreatic insufficiency?

Research shows that pancreatic enzyme replacement therapy, including Pancrelipase, is effective in preventing malnutrition and weight loss in patients with pancreatic insufficiency due to chronic pancreatitis or surgery. Studies have demonstrated its ability to improve nutritional status by aiding digestion in these patients. ^{1 2 3 4 5}

Is pancreatic enzyme replacement therapy safe for humans?

Pancreatic enzyme replacement therapy, including products like Creon and Zenpep, has been studied for safety in people with conditions like chronic pancreatitis and cystic fibrosis. These studies generally show that the therapy is safe for human use. ^{1 2 6 7 8}

How is the drug Pancrelipase unique for treating pancreatic insufficiency?

Pancrelipase is unique because it is a delayed-release formulation that helps improve digestion by providing enzymes like lipase, protease, and amylase, which are essential for breaking down fats, proteins, and carbohydrates. This formulation is designed to withstand stomach acid, ensuring the enzymes reach the small intestine where they are needed most. ^{1 2 3 9 10}

What is the purpose of this trial?

This study aims to evaluate if a 6-month course of pancrelipase (CREON) treatment improves symptoms of exocrine pancreatic insufficiency (EPI) after an attack of acute pancreatitis. Diagnosis of EPI is measured by a fecal elastase value of \<200, and patients must have a qualifying symptom burden based on the EPI symptom tracker survey. Blood and stool will be analyzed as part of this study, and other surveys of health status will be used to track improvement of symptoms.

Eligibility Criteria

This trial is for individuals who have had an acute pancreatitis attack and are now experiencing symptoms of exocrine pancreatic insufficiency (EPI), confirmed by a fecal elastase test showing less than 200. Participants should be willing to take pancrelipase capsules for six months and complete health surveys.

Inclusion Criteria

My weight is between 40 and 120 kg.

I have not taken any pancreatic enzymes for 7 days before my second visit.

I am not pregnant and will use birth control during and after the study as required.

Exclusion Criteria

I had acute pancreatitis because of a cyst, injury, surgery, or after an ERCP procedure.

I have pancreatic cancer or another cancer that needs treatment, but skin and early cervical cancers treated are okay.

I have a confirmed history of chronic pancreatitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Run-in

Participants complete a 7-day run-in period without any pancreatic enzyme replacement therapy and complete baseline questionnaires and assessments

1 week

1 visit (in-person)

Treatment

Participants receive pancrelipase (CREON) treatment for 180 days to improve symptoms of exocrine pancreatic insufficiency

26 weeks

Regular visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of EPI symptom burden, stool frequency, and consistency

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Pancrelipase

Trial Overview The study tests whether taking pancrelipase (CREON) for six months can improve EPI symptoms following acute pancreatitis. It involves regular blood and stool tests, as well as completing surveys to monitor symptom changes over the treatment period.

Participant Groups

Group I: Pancrelipase Experimental Treatment 1 Intervention

Pancrelipase (CREON) capsules taken orally with food, at a dose 36,000 units with snacks and 72,000 units with meals, for a total of 6 months (180 days)

Pancrelipase is already approved in United States, European Union for the following indications:

Approved in United States as Pancrelipase for:

• Exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy, pancreatic obstruction, and other pancreatic diseases

Approved in European Union as Pancrelipase for:

• Exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy, pancreatic obstruction, and other pancreatic diseases

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

University of Southern California

Collaborator

Trials

956

Recruited

1,609,000+

University of Illinois Chicago

Collaborator

Trials

1

Recruited

60+

New York University

Collaborator

Trials

249

Recruited

229,000+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Findings from Research

In a study involving 54 patients with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis or pancreatic surgery, pancrelipase significantly improved fat absorption (CFA) and nitrogen absorption (CNA) compared to placebo, indicating its efficacy in treating maldigestion.

The safety profile of pancrelipase was comparable to that of placebo, with similar rates of treatment-emergent adverse events, suggesting it is a safe option for patients with EPI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Whitcomb, DC., Lehman, GA., Vasileva, G., et al.[2022]

In a study of 58 patients with chronic pancreatitis and exocrine pancreatic insufficiency, pancreatic enzyme replacement therapy (PERT) using microencapsulated pancreatin significantly improved nutritional status, as indicated by increases in body mass index (BMI) in both patient groups over 8-12 months.

Laboratory markers of nutritional status, such as total protein, vitamin D, and magnesium, showed significant improvement, particularly in patients with abnormal nutritional status, highlighting the efficacy of PERT in enhancing overall health in these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effectiveness of pancreatic enzyme replacement therapy using microencapsulated pancreatin preparations in the correction of nutritional status in patients with chronic pancreatitis: a prospective observational study]. Bideeva, TV., Maev, IV., Kucheryavyy, YA., et al.[2020]

Pancreatic enzyme replacement therapy is crucial for patients with exocrine pancreatic insufficiency, particularly those who have undergone surgery, have chronic pancreatitis, or cystic fibrosis, with lipase being essential to reduce fat malabsorption (steatorrhoea).

Different formulations of pancreatic enzymes, including porcine pancreatin and enteric-coated preparations, have varying effectiveness and must be tailored to individual patient needs, highlighting the importance of understanding both the patient's condition and the specific characteristics of the enzyme supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacological aspects of pancreatic enzyme substitution therapy]. Löser, C., Fölsch, UR.[2006]

Pancreatic enzyme replacement therapy (PERT) significantly improves fat absorption in patients with chronic pancreatitis, with a coefficient of fat absorption increasing from 63.1 to 83.7, indicating its efficacy in treating exocrine pancreatic insufficiency.

PERT also enhances overall nutritional status and quality of life without significant adverse events, suggesting it is a safe and effective treatment, especially when higher doses or enteric-coated formulations are used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. de la Iglesia-García, D., Huang, W., Szatmary, P., et al.[2022]

A study of nine different pancreatic enzyme products showed that while most met the United States Pharmacopoeia (USP) standards for enzyme content, their ability to release lipase varied significantly, with some products failing to dissolve properly.

The findings suggest that substituting one pancreatic enzyme product for another may not be safe or effective, as differences in how well they release enzymes could lead to therapeutic failures, prompting the FDA to require approved new drug applications for all pancreatic enzyme products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme content and acid stability of enteric-coated pancreatic enzyme products in vitro. Case, CL., Henniges, F., Barkin, JS.[2019]

EUR-1008 (Zenpep) is an effective treatment for cystic fibrosis patients with exocrine pancreatic insufficiency, showing significant improvements in fat and nitrogen absorption compared to placebo in a study of 34 older patients.

The treatment was safe and well tolerated across all ages, with no serious drug-related adverse events reported, and it effectively controlled malabsorption symptoms in both younger and older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. Wooldridge, JL., Heubi, JE., Amaro-Galvez, R., et al.[2021]

ZENPEP (pancrelipase) significantly improves fat absorption in patients with chronic pancreatitis and exocrine pancreatic insufficiency, with both low and high doses showing better results than placebo in a study of 72 participants.

Patients with more severe exocrine pancreatic insufficiency benefited more from the high dose of ZENPEP, indicating that dosage may need to be adjusted based on the severity of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a novel pancreatic enzyme product, EUR-1008 (Zenpep), in patients with exocrine pancreatic insufficiency due to chronic pancreatitis. Toskes, PP., Secci, A., Thieroff-Ekerdt, R.[2021]

Pancreatic enzyme products (PEPs) like Creon, Zenpep, and Pancreaze are effective and safe treatments for exocrine pancreatic insufficiency (EPI) due to conditions such as cystic fibrosis, chronic pancreatitis, and pancreatectomy, with Creon being the first-line choice.

The FDA's review of PEPs revealed significant variability in response among unapproved products, leading to a requirement for all PEPs to undergo formal approval, ensuring their efficacy and safety in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic enzyme products: digesting the changes. Giuliano, CA., Dehoorne-Smith, ML., Kale-Pradhan, PB.[2011]

A study of eight pancreatin preparations available in Russia and the CIS found that all but one (Micrazim®) met the labeled lipase activity, indicating that most products are effective in delivering the necessary enzymes for digestion.

However, significant variability in particle size and dissolution rates among different brands and batches could affect the overall efficacy of pancreatic enzyme-replacement therapy (PERT), potentially impacting patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in In Vitro Properties of Pancreatin Preparations for Pancreatic Exocrine Insufficiency as Marketed in Russia and CIS. Maev, IV., Kucheryavyy, YA., Gubergrits, NB., et al.[2022]

Pancreatic enzyme replacement therapy (PERT) significantly improves fat absorption (CFA) in patients with exocrine pancreatic insufficiency (EPI), with a mean difference of 26.56 compared to baseline and 17.97 compared to placebo, based on a meta-analysis of 7 randomized controlled trials involving 282 patients.

The study found that PERT is effective and well-tolerated, with no significant differences in adverse events compared to placebo, suggesting it is a safe treatment option for EPI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta-analysis. Gan, C., Chen, YH., Liu, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. [2022]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The effectiveness of pancreatic enzyme replacement therapy using microencapsulated pancreatin preparations in the correction of nutritional status in patients with chronic pancreatitis: a prospective observational study]. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacological aspects of pancreatic enzyme substitution therapy]. [2006]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Enzyme content and acid stability of enteric-coated pancreatic enzyme products in vitro. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of a novel pancreatic enzyme product, EUR-1008 (Zenpep), in patients with exocrine pancreatic insufficiency due to chronic pancreatitis. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Pancreatic enzyme products: digesting the changes. [2011]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Differences in In Vitro Properties of Pancreatin Preparations for Pancreatic Exocrine Insufficiency as Marketed in Russia and CIS. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta-analysis. [2022]