A Phase 2, Placebo-Controlled, Randomized, Double-Blind Study of 2 Doses of Crofelemer for the Treatment of adult patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF) without colon in continuity (CIC).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Napo Therapeutics S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

10 Mar 2025 → ongoing

Decision date (initial)

2024-08-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Dose response

Assess the safety and tolerability of crofelemer in adult patients with Short Bowel Syndrome with Intestinal Failure (SBS-IF) without colon-in-continuity (CIC).
Evaluate the preliminary efficacy of crofelemer in adult patients with Short Bowel Syndrome with Intestinal Failure (SBS-IF) without colon-in-continuity (CIC).

Secondary objectives 4

1. Further assess the changes in parenteral support (calories, volume and electrolytes)
2. Assess the change in number of days/week of PS
3. Assess the change in volume of loose/watery stools and stool consistency
4. Further assess the safety and tolerability of crofelemer in adult patients with Short Bowel Syndrome with Intestinal Failure (SBS-IF) without colon-in-continuity (CIC)

Conditions and MedDRA coding

Short Bowel Syndrome and Intestinal Failure (SBS-IF) without colon-in-continuity (CIC

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003296-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 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;
2. Male and female patients aged ≥ 18 years;
3. SBS patients with intestinal failure and without colon-in-continuity,who are not eligible or not willing to receive an approved marketed GLP-2;
4. 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).
5. Minimum estimated remaining length of 60 cm of small bowel;
6. At least 6 months elapsed since last surgical bowel resection;
7. No restorative surgery planned during the entire study period;
8. Patients with at least 4 continuous months of PS dependency (total parenteral nutrition with or without intravenous fluids)
9. Chronic non-infectious diarrhoea defined as passage of at least 1 loose watery stool per day for more than 4 consecutive weeks.
10. 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;
11. Patients with Crohn’s disease must be in clinical remission for ≥ 12 weeks
12. Patients must be able to ingest solid or semi-solid foods and drink fluids;
13. 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;
14. 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.
15. 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);
16. Satisfactory general health status as determined by the investigator based on current clinical status, medical history and physical examination.

Exclusion criteria 23

1. Diagnosis of celiac disease or active or refractory tropical sprue;
2. Presence of clinically significant intestinal adhesions and/or chronic abdominal pain that can interfere with the conduct of the study;
3. Patients with current radiological (Radiography and/or CT) evidence of bowel dilatation or pseudo-obstruction;
4. Active Crohn’s disease as evaluated by standard procedures employed by the investigator;
5. 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;
6. Intestinal or other major surgery scheduled within the time frame of the study;
7. Visible blood in the stool within the last 12 weeks;
8. Clinical evidence of active radiation enteritis, or scleroderma, contributing to the patient's stool volume;
9. Compromised immune system (e.g., acquired immune deficiency syndrome [AIDS], severe combined immunodeficiency).
10. 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
11. Inadequate renal function: serum creatinine or blood urea nitrogen > 2 times the Upper Normal Limit (UNL).
12. Urine sodium <20 mmol/day;
13. 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.
14. 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.
15. Use of systemic corticosteroids, methotrexate, cyclosporine, tacrolimus, sirolimus, octreotide, intravenous glutamine within the last 4 weeks.
16. Use of antibiotics within the last week or active infection.
17. 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.
18. Pregnant or lactating women;
19. History of psychiatric illnesses which lead to consider the patient as incapacitated and prevent him/her to provide informed consent.
20. 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.
21. Patient not capable of understanding or not willing to adhere to the study visit schedules and other protocol requirements.
22. 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.
23. Known hypersensitivity/allergy to ANY component of the IP.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. S.1. Frequency of treatment-emergent adverse events (TEAEs)
2. S.2. Frequency of IP interruption and/or IP discontinuation and reason
3. E.1. Change in weekly volume of parenteral support (PS: TPN with or without IV fluid volume) from baseline to week 24 treatment period
4. E.2. Change in weekly stool volume from baseline to week 24

Secondary endpoints 9

1. E.3. Change from baseline in weekly volume of PS at week 2, 4, 8, 12, 16, 20 and 24
2. E.4. Change from baseline in weekly parenteral calories and electrolytes administered by PS at week 2, 4, 8, 12, 16, 20 and 24
3. E.5. Change from baseline in weekly oral fluid volume from baseline over the entire 24-week treatment period
4. E.6. Change in number of days/week of PS from baseline over the entire 24-week treatment period
5. E.7. Proportion of patients who achieve at least one day reduction in weekly PS or total weaning from PS over the entire 24-week treatment period
6. E.8. Change from baseline in weekly loose/watery stool volume over the entire 24-week treatment period
7. E.9. Change from baseline in stool consistency (according to Bristol Stool Scale) over the entire 24-week treatment period
8. S.3. Changes 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
9. S.4. Changes from baseline in physical examination findings at week 2, 4, 8, 12, 16, 20 and 24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Napo Therapeutics S.p.A.

Sponsor organisation

Napo Therapeutics S.p.A.

Address

Via Michele Barozzi 2

City

Milan

Postcode

20122

Country

Italy

Scientific contact point

Organisation

Napo Therapeutics S.p.A.

Contact name

Napo Therapeutics Clinical Operations Lead

Public contact point

Organisation

Napo Therapeutics S.p.A.

Contact name

Napo Therapeutics Clinical Operations Lead

Third parties 6

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications