Clinical trial NCT06477159: Pancreatic Enzyme Replacement Therapy for Acute Pancreatitis-Associated Exocrine Pancreatic Insufficiency
Official title: Pancreatic Enzyme Replacement Therapy for Acute Pancreatitis-Associated Exocrine Pancreatic Insufficiency: the PERT-AP Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Exocrine Pancreatic Insufficiency
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
name: University of Illinois Chicago
name: University of Southern California
name: New York University
name: AbbVie
First posted: 2024-06-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This is a prospective, multi-center, open-label, single-arm study of pancrelipase (CREON) in eligible outpatient adults following an episode of acute pancreatitis. Following study eligibility evaluation and informed consent, patients will complete a 7-day run-in period without any pancreatic enzyme replacement therapy and complete baseline questionnaires and assessments, followed by a 180-day treatment period with pancrelipase. The study will end after a final 30 day-post pancrelipase treatment observation period during which safety events will be collected, and EPI symptom burden as well as stool frequency and consistency will be assessed as primary outcomes.

Eligibility criteria: Inclusion Criteria:

1. Adult patients of age 18 or older, able to provide informed consent and follow all study procedures.
2. Stable outpatient up to 12 months following an acute pancreatitis episode and has EPI based on an FE-1 \< 200 µg/g stool obtained within 3 months prior to baseline assessment (Visit 2).
3. Score of equal or greater 0.6 on the EPI symptom tracker at baseline Visit 2.
4. Must be off PERT (including prescription and non-prescription enzymes) for 7 days prior to baseline Visit 2.
5. Must have fully completed the terminal intervention for necrotizing pancreatitis (surgical or endoscopic necrosectomy or percutaneous drainage).
6. Have a Body Weight between 40 and 120 kg (amounts to 600-1800 LU/meal pancrelipase starting dose of pancrelipase).
7. Women of childbearing potential must have a negative urine pregnancy test at Study Day 1 and practicing at least one protocol specified method of birth control (Section 5.2.4), starting at Study Day 1 through 30 days after last dose of pancrelipase.
8. Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined:

   * Age \> 55 years with no menses for 12 or more months without an alternative medical cause.
   * Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an FSH level \> 40 IU/L.

OR

* Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

do not require pregnancy testing.

Exclusion Criteria:

1. Acute pancreatitis episode due to a pancreatic cystic neoplasm, trauma, or surgery. Post-ERCP acute pancreatitis patients can be enrolled.
2. History of definite chronic pancreatitis defined by APA Chronic Pancreatitis Guideline.1
3. Pancreas malignancy or other active malignancies requiring systemic treatment; treated basal cell carcinoma, and treated in-situ cervical cancer can be included.
4. Enteropathies, and gastroenteritis that may affect FE-1 levels, e.g., Inflammatory bowel disease, Celiac Disease, viral-, bacterial-, fungal-, or parasitic gastroenteritis.
5. Gastroparesis.
6. Confirmed or suspected cystic tumor associated with main pancreatic duct dilation or believed to be the cause of AP (in the site-PI's judgment).
7. Prior pancreatic surgery or GI tract surgery affecting the upper GI tract including but not limited to gastric bypass surgery, total pancreatectomy.
8. Pregnancy or breast feeding.
9. Patients with life expectancy of less than 6 months due to advanced chronic conditions, such as congestive heart failure or chronic obstructive pulmonary disease, or other conditions which preclude study participation by judgement of the investigator.
10. Incarcerated individuals

Primary outcomes:
measure: Patient-Reported EPI Symptoms - Short Term
timeFrame: 30 days
Secondary outcomes:
measure: Patient-Reported EPI Symptoms - LongTerm
timeFrame: 180 days
measure: Change in Stool Frequency
timeFrame: 180 days
measure: Change in Stool Consistency
timeFrame: 180 days
measure: Change in Depression Score
timeFrame: 180 days
measure: Change in SF-12 Health Score
timeFrame: 180 days
measure: Change in Global Health Score
timeFrame: 180 days
measure: Medication Adherence
timeFrame: 180 days
measure: Change in Nutrition Biomarkers - Vitamin D
timeFrame: 180 days
measure: Change in Nutrition Biomarkers - Retinol Binding Protein
timeFrame: 180 days
measure: Change in Nutrition Biomarkers - Pre-albumin
timeFrame: 180 days
measure: Change in Nutrition Biomarkers - Albumin
timeFrame: 180 days
Other outcomes:
measure: Frequency, Type, and Severity of Adverse Events
timeFrame: 210 days
measure: Patient-Reported EPI Symptoms - Post-Treatment
timeFrame: 210 days
measure: Change in Stool Frequency
timeFrame: 210 days
measure: Change in Stool Consistency
timeFrame: 210 days
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Chicago
country: United States
facility: University of Illinois Chicago
state: Illinois
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
References: