MS1819-SD phase II clinical trial for Exocrine Pancreatic Insufficiency caused by Cystic Fibrosis.

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2018-003831-31-HU
• Date of registration: 09/10/2018
• Prospective Registration: Yes
• Primary sponsor: AzurRx
• Public title: MS1819-SD phase II clinical trial for Exocrine Pancreatic Insufficiency caused by Cystic Fibrosis.
• Scientific title: A multicenter, open-label Phase 2 study with escalating doses of MS1819-SD on top of a stable dose of PPEs, to investigate the efficacy and safety of this combination for the compensation of severe exocrine pancreatic insufficiency in CF patients not fully compensated with only PPEs - MS1819/18/02
• Date of first enrolment: 28/03/2019
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003831-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Escalating doses sheme; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Hungary, Poland, Spain

Contacts

• Name: R&D Program Director
• Affiliation: AzurRx

• Name: R&D Program Director
• Affiliation: AzurRx

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed and dated informed consent form.
2. Age = 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 = 18.0 kg/m2 for female or male patients
b. BMI < 10th percentile for patients 12 to < 18 years of age based on growth charts published by the Word Health Organization (WHO)
6. Cystic fibrosis (CF), based on at least 2 clinical features consistent with CF in the opinion of the investigator and a sweat chloride concentration > 60 mmol/L by pilocarpine iontophoresis.
7. Fecal pancreatic elastase-1 < 100 µg/g of stools at screening.
8. Baseline CFA < 80% with a maximum daily dose of 10,000 lipase units/kg/day as recommended by the international guidelines and CF Societies.
9. Clinically stable with no documented evidence of significant respiratory symptoms that would require administration of intravenous antibiotics, oxygen supplementation, or hospitalization within the 30 days of screening.
10. Male and female patients, if of childbearing potential, must use a reliable method of contraception during the study. A reliable method of birth control is defined as one of the following: oral or injectable contraceptives, intrauterine device, contraceptive implants, tubal ligation, hysterectomy, or a double-barrier method (diaphragm with spermicidal foam or jelly, or a condom), abstinence or vasectomy. Periodic abstinence (calendar, symptom-thermal, or post-ovulation methods) is not an acceptable method of contraception. The preferred and usual lifestyle of the patient must also be evaluated in determining if sexual abstinence is a reliable method of birth control.
11. Be considered as reliable and capable of adhering to the protocol, according to the judgment of the investigator.

Are the trial subjects under 18? yes
Number of subjects for this age range: 8
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 symtoms 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 = 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Exocrine Pancreatic Insufficiency
MedDRA version: 20.0 Level: LLT Classification code 10033628 Term: Pancreatic insufficiency System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: MS1819-SD
Pharmaceutical Form: Capsule, hard

Primary Outcome(s)

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.

Secondary Objective: Not Applicable

Timepoint(s) of evaluation of this end point: V4 - V5 and V6

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 Outcome(s)

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

Secondary ID(s)

MS1819/18/02

Source(s) of Monetary Support

AzurRx

Ethics review

Status: Approved
Approval date: 29/01/2019
Contact: