CROFELEMER for Short bowel syndrome and intestinal failure (SBS-IF) without colon in continuity (CIC)

Inclusion criteria

• {"criterion_text":"- Patients must understand and provide written informed consent before they can participate in the study. They must understand the study procedures and be willing to complete the required assessments;"}
• {"criterion_text":"- Patients receiving total parenteral nutrition (TPN) for at least three days per week and a minimum of 2 liters of TPN per week, to meet caloric, fluid or electrolytes needs;"}
• {"criterion_text":"- Patients with Crohn’s disease must be in clinical remission for ≥ 12 weeks"}
• {"criterion_text":"- Patients must be able to ingest solid or semi-solid foods and drink fluids;"}
• {"criterion_text":"- If taken at screening, use of antimotility and antidiarrheal agents (loperamide, diphenoxylate, codeine and other opiates), H2-receptor antagonists, proton pump inhibitors, bile sequestering agents, oral glutamine, diuretics and oral rehydration solutions is required to be at stable average weekly doses for at least 4 weeks prior to screening evaluations;"}
• {"criterion_text":"- If female and of child-bearing potential, the patient must use an “acceptable effective contraceptive measure” for the entire study duration and for 4 weeks after the last dose. Acceptable birth control methods that result in a failure rate of more than 1% per year include: progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action male or female condom with or without spermicide cap, diaphragm or sponge with spermicide (A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable). Male patients must agree to use an acceptable form of birth control and to not donate sperm during the study and for 4 weeks after the last dose."}
• {"criterion_text":"- If female and of child-bearing potential, the patient must have a negative urine pregnancy test prior the first administration of the investigational product (IP);"}
• {"criterion_text":"- Satisfactory general health status as determined by the investigator based on current clinical status, medical history and physical examination."}
• {"criterion_text":"- Male and female patients aged ≥ 18 years;"}
• {"criterion_text":"- SBS patients with intestinal failure and without colon-in-continuity,who are not eligible or not willing to receive an approved marketed GLP-2;"}
• {"criterion_text":"- Patients with history of SBS resulting in intestinal failure caused by a major intestinal resection (e.g., injury, cancer*, Crohn’s disease, vascular disease, volvulus) without colon-in-continuity (patients with duodenostomy, jejunostomy or ileostomy). Intestinal failure will be defined according to the recommendations of the European Society for Clinical Nutrition and Metabolism (ESPEN), i.e. a reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous (IV) supplementation is required to maintain health and/or growth. *Patients with history of cancer, should be in remission for the last 6 months and should not be receiving ongoing anticancer therapy (longterm hormonal therapy is allowed)."}
• {"criterion_text":"- Minimum estimated remaining length of 60 cm of small bowel;"}
• {"criterion_text":"- At least 6 months elapsed since last surgical bowel resection;"}
• {"criterion_text":"- No restorative surgery planned during the entire study period;"}
• {"criterion_text":"- Patients with at least 4 continuous months of PS dependency (total parenteral nutrition with or without intravenous fluids)"}
• {"criterion_text":"- Chronic non-infectious diarrhoea defined as passage of at least 1 loose watery stool per day for more than 4 consecutive weeks."}

Exclusion criteria

• {"criterion_text":"- Diagnosis of celiac disease or active or refractory tropical sprue;"}
• {"criterion_text":"- Inadequate hepatic function: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or total bilirubin and/or alkaline phosphatases > 2 times the patient’s average relative values in the last 3 months"}
• {"criterion_text":"- Inadequate renal function: serum creatinine or blood urea nitrogen > 2 times the Upper Normal Limit (UNL)."}
• {"criterion_text":"- Urine sodium <20 mmol/day;"}
• {"criterion_text":"- More than four SBS-related hospital admissions (unless admissions were to rule out line sepsis) within the past 12 months or hospital admission within the last 4 weeks."}
• {"criterion_text":"- Concurrent or past use of infliximab, growth hormone or growth factors such as native glucagon-like peptide-2 (GLP-2) or other biological therapy within the last 12 weeks."}
• {"criterion_text":"- Use of systemic corticosteroids, methotrexate, cyclosporine, tacrolimus, sirolimus, octreotide, intravenous glutamine within the last 4 weeks."}
• {"criterion_text":"- Use of antibiotics within the last week or active infection."}
• {"criterion_text":"- History of alcohol abuse (Drinking more than 12 g/day of alcohol for women and 24 g/day of alcohol for men) or drug abuse within the last year."}
• {"criterion_text":"- Pregnant or lactating women;"}
• {"criterion_text":"- History of psychiatric illnesses which lead to consider the patient as incapacitated and prevent him/her to provide informed consent."}
• {"criterion_text":"- Presence of clinically significant intestinal adhesions and/or chronic abdominal pain that can interfere with the conduct of the study;"}
• {"criterion_text":"- History of any other uncontrolled chronic or acute concomitant disease which, in the Investigator’s opinion, would contraindicate study participation or confound interpretation of the results."}
• {"criterion_text":"- Patient not capable of understanding or not willing to adhere to the study visit schedules and other protocol requirements."}
• {"criterion_text":"- Participation in any other interventional clinical study within five times the half-life of the investigational medicinal product / relevant metabolites (of the previous clinical study) or 4 weeks (whichever is longer) prior to screening."}
• {"criterion_text":"- Known hypersensitivity/allergy to ANY component of the IP."}
• {"criterion_text":"- Patients with current radiological (Radiography and/or CT) evidence of bowel dilatation or pseudo-obstruction;"}
• {"criterion_text":"- Active Crohn’s disease as evaluated by standard procedures employed by the investigator;"}
• {"criterion_text":"- Inflammatory bowel disease (IBD) that requires immunosuppressant therapy that has been introduced or changed within last 3 months or treatment with biologics within the last 6 months;"}
• {"criterion_text":"- Intestinal or other major surgery scheduled within the time frame of the study;"}
• {"criterion_text":"- Visible blood in the stool within the last 12 weeks;"}
• {"criterion_text":"- Clinical evidence of active radiation enteritis, or scleroderma, contributing to the patient's stool volume;"}
• {"criterion_text":"- Compromised immune system (e.g., acquired immune deficiency syndrome [AIDS], severe combined immunodeficiency)."}

Primary endpoints

• {"endpoint_text":"- S.1.\tFrequency of treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Frequency (count and incidence) of treatment-emergent adverse events (TEAEs) reported during the study."}
• {"endpoint_text":"- S.2.\tFrequency of IP interruption and/or IP discontinuation and reason","definition_or_measurement_approach":"Count and frequency of investigational product (IP) interruptions and discontinuations and recorded reasons for these events."}
• {"endpoint_text":"- E.1.\tChange in weekly volume of parenteral support (PS: TPN with or without IV fluid volume) from baseline to week 24 treatment period","definition_or_measurement_approach":"Change from baseline to week 24 in weekly volume of parenteral support (measured in volume units as recorded at baseline and at week 24)."}
• {"endpoint_text":"- E.2.\tChange in weekly stool volume from baseline to week 24","definition_or_measurement_approach":"Change from baseline to week 24 in weekly stool volume (measured as stool volume recorded at baseline and at week 24)."}

Secondary endpoints

• {"endpoint_text":"- E.3.\tChange from baseline in weekly volume of PS at week 2, 4, 8, 12, 16, 20 and 24","definition_or_measurement_approach":"Change from baseline in weekly parenteral support volume measured at specified timepoints (weeks 2, 4, 8, 12, 16, 20, 24)."}
• {"endpoint_text":"- E.4.\tChange from baseline in weekly parenteral calories and electrolytes administered by PS at week 2, 4, 8, 12, 16, 20 and 24","definition_or_measurement_approach":"Change from baseline in weekly parenteral calories and electrolytes administered (measured at weeks 2, 4, 8, 12, 16, 20, 24)."}
• {"endpoint_text":"- E.5.\tChange from baseline in weekly oral fluid volume from baseline over the entire 24-week treatment period","definition_or_measurement_approach":"Change from baseline in weekly oral fluid intake measured over the 24-week treatment period."}
• {"endpoint_text":"- E.6.\tChange in number of days/week of PS from baseline over the entire 24-week treatment period","definition_or_measurement_approach":"Change from baseline in the number of days per week patients receive parenteral support, measured over 24 weeks."}
• {"endpoint_text":"- E.7.\tProportion of patients who achieve at least one day reduction in weekly PS or total weaning from PS over the entire 24-week treatment period","definition_or_measurement_approach":"Proportion (percentage) of patients achieving ≥1 day reduction in weekly PS or complete weaning from PS during the 24-week period."}
• {"endpoint_text":"- E.8.\tChange from baseline in weekly loose/watery stool volume over the entire 24-week treatment period","definition_or_measurement_approach":"Change from baseline in weekly loose/watery stool volume measured across the 24-week treatment period."}
• {"endpoint_text":"- E.9.\tChange from baseline in stool consistency (according to Bristol Stool Scale) over the entire 24-week treatment period","definition_or_measurement_approach":"Change from baseline in stool consistency assessed by the Bristol Stool Scale over 24 weeks."}
• {"endpoint_text":"- S.3.\tChanges from baseline in safety laboratory parameters (in particular for liver and renal function, glucose and lipids) at week 2, 4, 8, 12, 16, 20 and 24","definition_or_measurement_approach":"Changes from baseline in specified laboratory safety parameters measured at the listed timepoints (weeks 2,4,8,12,16,20,24)."}
• {"endpoint_text":"- S.4.\tChanges from baseline in physical examination findings at week 2, 4, 8, 12, 16, 20 and 24","definition_or_measurement_approach":"Changes from baseline in physical examination findings recorded at specified study visits (weeks 2,4,8,12,16,20,24)."}

Germany

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

19-11-2025

Processing Time Days

482

Number Of Sites

5

Number Of Participants

11

Italy

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

23-12-2025

Processing Time Days

512

Number Of Sites

3

Number Of Participants

11

Primary sponsor

Full Name

Napo Therapeutics S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Arithmos S.r.l.","duties_or_roles":"sponsorDuties codes: [8]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Sannova Analytical LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Merative US LP","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Alira Health GmbH","duties_or_roles":"sponsorDuties codes: [1,10,11,5,6,8]","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Manufacturing Packaging Farmaca (MPF) B.V.","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Obvio Health USA Inc.","duties_or_roles":"sponsorDuties codes: [15]; responsibilities: patient diary and questionnaire","organisation_type":"Pharmaceutical company"}