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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a 6-month course of pancrelipase (CREON) can improve symptoms for individuals with exocrine pancreatic insufficiency (EPI) following an acute pancreatitis attack. EPI occurs when the pancreas fails to produce enough enzymes for proper digestion, causing stomach pain, gas, and oily stools. The trial seeks participants who have experienced these symptoms and have a specific EPI diagnosis, confirmed by a fecal test, after a recent pancreatitis episode. Participants will take pancrelipase capsules with meals and snacks for 6 months to assess symptom improvement. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for pancrelipase?

Studies have shown that pancrelipase, the treatment being tested, is safe and generally well-tolerated. Research indicates that pancrelipase, also known as CREON, effectively treats exocrine pancreatic insufficiency (EPI) in both adults and children. One study found it safe and well-tolerated in individuals with EPI due to cystic fibrosis. Another study confirmed that most patients tolerate pancrelipase well. As this trial is in a later phase, the treatment's safety has already been evaluated in many individuals, providing more confidence in its safety for new participants. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Pancrelipase is unique because it offers a tailored enzyme replacement specifically for those with pancreatic insufficiency. Unlike some other treatments that may offer generic enzyme support, pancrelipase (CREON) is designed to closely mimic the natural enzymes produced by the pancreas, improving digestion and nutrient absorption. Researchers are excited about its potential to provide more efficient relief with its specific dosing regimen, offering 36,000 units with snacks and 72,000 units with meals, which could lead to better management of symptoms over the six months of treatment.

What is the effectiveness track record for pancrelipase in treating exocrine pancreatic insufficiency?

Studies have shown that pancrelipase, also known as CREON, effectively treats exocrine pancreatic insufficiency (EPI). EPI occurs when the pancreas doesn't produce enough enzymes for digestion. Research indicates that pancrelipase provides these missing enzymes. In previous studies, pancrelipase improved symptoms in people with EPI, making food digestion easier. This treatment is also safe and well-tolerated. Overall, clinical data supports its use for improving digestion problems related to EPI. Participants in this trial will receive pancrelipase to further evaluate its effectiveness and safety over a 6-month period. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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.

Score of equal or greater 0.6 on the EPI symptom tracker at baseline Visit 2

Exclusion Criteria

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

Pregnancy or breast feeding

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39299226/

Clinical Efficacy and Safety of Treatments for Exocrine ... This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and ...

2. medicaid.nv.gov medicaid.nv.gov/Downloads/provider/Pancreatic_Enzymes_2021-09.pdf

Therapeutic Class Overview - Pancreatic Enzymes Efficacy and tolerability of a new formulation of pancrelipase delayed-release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency ...

3. aetna.com aetna.com/products/rxnonmedicare/data/2024/Pancrelipase_PA_Policy_3134-A_UDR_10-2023.html

Pancrelipase PA Policy 3134-A UDR 10-2023 Pancrelipase is not effective in the treatment of functional digestive disorders unrelated to pancreatic insufficiency.6. Place of Service: Outpatient The ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1569199309001222

Efficacy and safety of Creon® 24000 in subjects with ... This study demonstrated Creon was effective in treating EPI due to CF and was safe and well tolerated.

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04098237

Pancreaze (Pancrelipase) for Patients With Pancreatic ... The objective of this study is to assess weight stability, functional changes, and quality of life when Pancreaze (pancrelipase) delayed-release ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/022542Orig1s007.pdf

center for drug evaluation and research - accessdata.fda.gov The short-term safety and efficacy of VIOKACE were evaluated in a randomized, double-blind, placebo-controlled, parallel group study comparing ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00676702

A Study of the Enzyme Activity and Safety of Pancrelipase ... A Study of the Enzyme Activity and Safety of Pancrelipase in Patients With Severe Exocrine Pancreatic Insufficiency (EPI). ClinicalTrials.gov ...