Exocrine Pancreatic Insufficiency MedDRA version: 20.0 Level: LLT Classification code 10033628 Term: Pancreatic insufficiency System Organ Class: 100000004856
Conditions
Interventions
Product Name: MS1819-SD
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lipase Lip2 from Yarrowia lipolytica
Other descriptive name: LIPASE LIP2
Concentration unit: mg milligram(s)
Concentrati
Sponsors
AzurRx
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated informed consent form. 2. Age > or = 12 years at the time of screening 3. Male or female. 4. Under stable dose of PPE = 1 month. Stable dose is defined as dose of medication not changed during this time period and the medication must be commercially available and be administered in the recommended dose range. 5. A nutritional status as defined by: a. BMI 60 mmol/L by pilocarpine iontophoresis. 7. Fecal pancreatic elastase-1 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Established or suspected fibrosing colonopathy. 2. Total or partial gastrectomy. 3. A history of solid organ transplant or significant surgical resection of the bowel; significant resection of the bowel is defined as any resection of the terminal ileum or ileocecal valve. Patients who have had qualitative, long-term changes in nutritional status after any other bowel resection (eg, increased of new need for pancreatic enzyme supplementation compared with preoperative status to maintain the same nutritional status) should also be excluded. 4. Any chronic diarrheal illness unrelated to pancreatic insufficiency (eg, infectious gastroenteritis, sprue, inflammatory bowel disease) 5. Known hypersensitivity or other severe reaction to any ingredient of the investigational medicinal product (IMP). 6. Bilirubin > 1.5 times upper limit normal (ULN). 7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times ULN. 8. Alkaline phosphatase (ALP) > 5 times ULN. 9. Gamma glutamyltransferase (GGT) > 5 times ULN. 10. Signs and/or symptoms of liver cirrhosis or portal hypertension (eg, splenomegaly, ascites, esophageal varices), or documented liver disease unrelated to CF 11. Known allergy to the stool marker. 12. Feeding via an enteral tube during 6 months before screening 13. Routine use of anti-diarrheals, anti-spasmodics, or cathartic laxatives, or a change in chronic osmotic laxatives (eg, polyethylene glycol) regimen in the previous laxative therapy within the last 12 months before screening 14. History of severe constipation with < 1 evacuation/week under appropriate laxative therapy within the last 12 months before screening. 15. Documentation of distal intestinal pseudo-obstruction syndrome within the last 12 months before screening. 16. Forced Expiratory Volume < or = 30% at the screening visit. 17. Lactation or known pregnancy or positive pregnancy test at both screening and baseline for women of childbearing potential. 18. Participation in another clinical study involving an IMP within 30 days before inclusion or concomitantly with this study. 19. Poorly controlled diabetes according the investigator’s judgement.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary efficacy objective: To determine the efficacy of escalating doses of MS1819-SD on top of a stable dose of Porcine Pancreatic Extracts (PPEs) on triglyceride digestion assessed by coefficient of fat absorption (CFA) in patients with severe Exocrine Pancreatic Insufficiency (EPI) caused by cystic fibrosis (CF) and not fully compensated with only PPEs. Primary safety objective: To assess the safety and tolerability of escalating doses of MS1819-SD on top of a stable dose of PPEs in patients with severe EPI caused by CF.;Secondary Objective: Not Applicable;Primary end point(s): Primary Efficacy Endpoint: • Change in CFA from baseline (V2) to visits of phase C (V4, V5 and V6). Primary Safety Endpoints: Safety data, including all observed AEs with a particular focus on immunoallergic events and digestive symptomatology.;Timepoint(s) of evaluation of this end point: V4 - V5 and V6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: Key secondary endpoints: • Change from Phase B in the mean number of daily evacuations during the days of the stool collection period in each cycle in Phase C. • Change from Phase B in the mean consistency of stools assessed by the Bristol scale during the stool collection period in each cycle in Phase C. Secondary Safety Endpoints In addition to primary safety endpoints, laboratory test results will be summarized: • Fasting glucose. • Urinalysis • Hematology: Hematocrit, Hemoglobin, Erythrocyte count (RBC), Leukocytes (WBC), Absolute counts of: Neutrophils (segmented), Neutrophils juvenile (bands), Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets. • Biochemistry: Serum concentration of: Sodium, Potassium, Chloride, Bicarbonate, Blood urea nitrogen (BUN), Total Calcium, Phosphorus, Magnesium, Albumin, Prealbumin, Total protein, Creatinine, Alkaline phosphatase, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Lactate deshydrogenase (LDH), Total bilirubin, Direct bilirubin, Uric Acid. • Fasting Lipid Profile: Total cholesterol, Triglycerides, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL) and Very Low Density Lipoprotein (VLDL) • Serum vitamins A, D, E and K. • Activated partial thromboplastin time (aPTT), Prothrombin time/International normalized ratio (PT/INR) • Immunogenic assessment for circulating levels of LIP2 lipase. • Antibodies against LIP2.;Timepoint(s) of evaluation of this end point: V4 - V5 and V6 | — |
Countries
Hungary, Poland, Spain
Contacts
Public ContactR&D Program Director
AzurRx
Outcome results
None listed