Safety and Efficacy of Crofelemer in Adult Patients With Short Bowel Syndrome and Intestinal Failure (SBS-IF) Without Colon-in-continuity (CIC)

NCT06904872 | Recruiting Phase 2

• 2 other identifiers: NP303-5012024-511994-31-00
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 8

Brief Summary

A 24-week, randomized, placebo-controlled, double-blind study to evaluate the efficacy, safety and tolerability of crofelemer in patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF) without colon-in-continuity (CIC) requiring parenteral support (PS). Blinded study drug will be administered orally (or enterally) three times daily (TID) as a novel crofelemer formulation, Crofelemer Powder for Oral Solution, or a matching placebo powder formulation for oral solution. Patients will be randomized in a 1:1:1 ratio to crofelemer 3 mg/kg/dose TID, crofelemer 10 mg/kg/dose TID or placebo and randomization will be stratified by baseline PS volume (≤4 or \>4 L/week).

Conditions

Short Bowel Syndrome; Malabsorption Syndromes; Short Gut Syndrome; Post-Op Complication; Functional Gastrointestinal Disorders

Keywords

Short Bowel Syndrome

Outcome Measures

Primary Outcomes (4)

• Safety and Tolerability

  Frequency of Treatment-Emergent-Adverse Events

  24 weeks

• Safety and Tolerability

  Frequency of IP interruption and/or discontinuation considered related to the study drug

  24 weeks

• Preliminary Efficacy

  Change in weekly parenteral support (PS: parenteral nutrition (PN) and/or intravenous (IV) fluid volume) from baseline, by recording PS volume in the patient daily diary

  24 weeks

• Preliminary Efficacy

  Change in weekly stool volume from baseline, by measuring and recording daily stool volume in the patient daily diary

  24 weeks

Secondary Outcomes (10)

• Change in parenteral support volume

  24 weeks

• Change in parenteral support calories intake

  24 weeks

• Change in parenteral support electrolytes intake

  24 weeks

• Change in weekly oral fluid volume intake

  24 weeks

• Proportion of patients with change in number of days/week of PS

  24 weeks

Other Outcomes (1)

• Changes in Quality of life (QoL)

  24 weeks

Study Arms (3)

Crofelemer 3 mg/kg/dose three times daily (TID)

EXPERIMENTAL

Participants randomized to the Crofelemer 3 mg/kg/dose arm will receive Crofelemer 3 mg/kg/dose by oral route three times per day (TID) morning, midday, and evening for 24 weeks.

Drug: Crofelemer Powder for Oral Solution

Crofelemer 10 mg/kg/dose three times daily (TID)

EXPERIMENTAL

Participants randomized to the Crofelemer 10 mg/kg/dose arm will receive Crofelemer 10 mg/kg/dose by oral route three times per day (TID) morning, midday, and evening for 24 weeks.

Drug: Crofelemer Powder for Oral Solution

Matched Placebo three times per day (TID)

PLACEBO COMPARATOR

Participants randomized to the matched placebo arm will receive matched placebo by oral route three times per day (TID) morning, midday, and evening for 24 weeks.

Drug: Matched Placebo Powder for Oral Solution

Interventions

Crofelemer Powder for Oral Solution DRUG

Crofelemer Powder for Oral Solution

Crofelemer 10 mg/kg/dose three times daily (TID); Crofelemer 3 mg/kg/dose three times daily (TID)

Matched Placebo Powder for Oral Solution DRUG

Matched Placebo Powder for Oral Solution

Matched Placebo three times per day (TID)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be enrolled in the study if they meet all the following criteria:
• 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;
• Male and female patients aged ≥ 18 years;
• SBS patients with intestinal failure and without colon-in-continuity who are not eligible or not willing to receive an approved marketed GLP-2;
• 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 with not ongoing anticancer therapy (long-term hormonal therapy is allowed).
• Minimum remaining length of 100 cm of small bowel;
• At least 6 months elapsed since last surgical bowel resection;
• No restorative surgery planned during the entire study period;
• Patients with at least 4 continuous months of PS dependency (parenteral nutrition and/or intravenous fluids);
• Chronic non-infectious diarrhoea defined as passage of at least 1 loose watery stool per day for more than 4 consecutive weeks.
• Patients receiving stable parenteral support (fluids, electrolytes and/or nutrients) at least three days per week and a minimum of 2 liters of PS per week, to meet caloric, fluid or electrolytes needs;
• Patients with Crohn's disease will have to be in clinical remission for ≥ 12 weeks;
• Patients must be able to ingest solid or semi-solid foods and drink fluids;
• 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;
• 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.

You may not qualify if:

• Patients cannot be enrolled in the study if they meet any of the following criteria:
• Body mass index (BMI) \<17.5 or \>30 kg/m2;
• Presence of clinically significant intestinal adhesions and/or chronic abdominal pain that can interfere with the conduct of the study;
• Patients with radiological (Radiography and/or CT) signs of bowel dilatation or pseudo-obstruction;
• Active Crohn's disease as evaluated by standard procedures employed by the investigator;
• Inflammatory bowel disease (IBD) that required immunosuppressant therapy that has been introduced or changed within last 3 months or treatment with biologics within the last 6 months;
• Intestinal or other major surgery scheduled within the time frame of the study;
• Visible blood in the stool within the last 12 weeks;
• Ongoing radiation enteritis or the presence of damaged enteral tissue due to radiation enteritis, scleroderma, celiac disease, refractory or tropical sprue;
• Compromised immune system (e.g., acquired immune deficiency syndrome \[AIDS\], severe combined immunodeficiency);
• 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;
• Inadequate renal function: serum creatinine or blood urea nitrogen \> 2 times the Upper Normal Limit (UNL);
• Urine sodium \<20 mmol/day;
• More than four SBS-related hospital admissions (unless one or more admissions were to rule out line sepsis) within the past 12 months or hospital admission within the last 4 weeks;
• 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;

Sponsors & Collaborators

• Napo Therapeutics, S.p.A.: lead

Study Sites (8)

Universitäatsklinik RWTH

Aachen, 52074, Germany

NOT YET RECRUITING

Charité Universitätsmedizin

Berlin, 10117, Germany

NOT YET RECRUITING

Universitätsklinikum

Essen, 45147, Germany

NOT YET RECRUITING

Asklepios Klinik St. Georg

Hamburg, 20099, Germany

NOT YET RECRUITING

Universitätsmedizin

Rostock, 18057, Germany

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

RECRUITING

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

RECRUITING

Ospedale Università di Padova

Padua, 35128, Italy

NOT YET RECRUITING

Related Publications (28)

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MeSH Terms

Conditions

Short Bowel Syndrome; Malabsorption Syndromes; Postoperative Complications; Gastrointestinal Diseases

Interventions

Solutions

Condition Hierarchy (Ancestors)

Intestinal Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Central Study Contacts

Sabriye Duran

CONTACT

+49 089 89558070; sabriye.duran@alirahealth.com

Sara Papetti, MA

CONTACT

+39 3397978779; spapetti@napo.eu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible patients who have met the stabilization criteria above will be randomized to one of the following treatment groups and entered into the 24-week double-blind treatment period: * Crofelemer 3 mg/kg/dose TID, morning, midday and evening; * Crofelemer 10 mg/kg/dose TID, morning, midday and evening; * Matched placebo TID, morning, midday and evening.

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: April 1, 2025
• Study Start: May 29, 2025
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5); IT (3)