Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Microvillus Inclusion Disease (MVID)

NCT06721871 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NP303-104
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 3

Brief Summary

a 32-week study that will evaluate the safety, tolerability and preliminary efficacy of multiple ascending doses of crofelemer, compared to placebo, using a randomized cross-over design within each dose level, when administered to participants with MVID receiving parenteral support (PS, defined as TPN with or without supplementary IV fluid requirements). Blinded study drug will be administered as a novel crofelemer formulation, Crofelemer Powder for Oral Solution, or a matching placebo powder formulation for oral solution. Assigned study drug will be reconstituted and administered orally (or enterally) three times daily (TID) as a concentrated liquid formulation in each of the three dose levels

Conditions

Microvillus Inclusion Disease; Congenital Disorders; Rare Diseases

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability

  Incidence of Adverse Events and Serious Adverse Events

  32 Weeks

• Changes in Physical Examination

  Changes from baseline in physical exam and signs of dehydration, such as decreased urine output, sunken eyes, lethargy and abnormal skin turgor.

  32 Weeks

• Changes in laboratory Values

  Incidence in changes from baseline of individual lab values within a chemistry, hematology and metabolic panel analysis.

  32 Weeks

Secondary Outcomes (6)

• Average Daily Loose/Watery Stool Volume

  Average Weekly for 32 weeks

• Average Daily Stool Frequency

  Average Weekly for 32 weeks

• Average Daily Stool Consistency

  Average Weekly for 32 weeks

• Stool Electrolyte

  Average Weekly for 32 weeks

• PS Volume Requirements

  Average Weekly for 32 weeks

Study Arms (12)

Dose Level 1/Treatment Period 1: 1mg/kg/dose 3x/day

EXPERIMENTAL

Participants may be randomized to crofelemer powder for oral solution during Treatment Period 1 (1 month duration)

Drug: Crofelemer Powder for Oral Solution

Dose Level 1/Treatment Period 1: Placebo 3x/day

PLACEBO COMPARATOR

Participants may be randomized to the placebo comparator during Treatment Period 1 (1 month duration)

Drug: Placebo Powder for Oral Solution

Dose Level 1/Treatment Period 2: 1mg/kg/dose 3x/day

EXPERIMENTAL

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Drug: Crofelemer Powder for Oral Solution

Dose Level 2/Treatment Period 1: 3mg/kg/dose 3x/day

EXPERIMENTAL

Participants will crossover to either crofelemer powder for oral solution or placebo comparator or continue on crofelemer powder for oral solution or the placebo comparator that they were previously on during Dose Level 1 (1 month duration)

Drug: Crofelemer Powder for Oral Solution

Dose Level 2/Treatment Period 1: Placebo 3x/day

PLACEBO COMPARATOR

Participants will crossover to either crofelemer powder for oral solution or placebo comparator or continue on crofelemer powder for oral solution or the placebo comparator that they were previously on during Dose Level 1 (1 month duration)

Drug: Placebo Powder for Oral Solution

Dose Level 2/Treatment Period 2: 3mg/kg/dose 3x/day

EXPERIMENTAL

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Drug: Crofelemer Powder for Oral Solution

Dose Level 2/Treatment Period 2: Placebo 3x/day

PLACEBO COMPARATOR

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Drug: Placebo Powder for Oral Solution

Dose Level 3/Treatment Period 1: 10mg/kg/dose 3x/day

EXPERIMENTAL

Participants will crossover to either crofelemer powder for oral solution or placebo comparator or continue on crofelemer powder for oral solution or the placebo comparator that they were previously on during Dose Level 2 (1 month duration)

Drug: Crofelemer Powder for Oral Solution

Dose Level 3/Treatment Period 1: Placebo 3x/day

PLACEBO COMPARATOR

Participants will crossover to either crofelemer powder for oral solution or placebo comparator or continue on crofelemer powder for oral solutionor the placebo comparator that they were previously on during Dose Level 2 (1 month duration)

Drug: Placebo Powder for Oral Solution

Dose Level 3/Treatment Period 2: 10mg/kg/dose 3x/day

EXPERIMENTAL

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Drug: Crofelemer Powder for Oral Solution

Dose Level 3/Treatment Period 2: Placebo 3x/day

PLACEBO COMPARATOR

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Drug: Placebo Powder for Oral Solution

Dose Level 1/Treatment Period 2: Placebo 3x/day

PLACEBO COMPARATOR

Participants will crossover to either crofelemer powder for oral solution or placebo comparator

Drug: Placebo Powder for Oral Solution

Interventions

Crofelemer Powder for Oral Solution DRUG

Crofelemer Powder for Oral Solution

Dose Level 1/Treatment Period 1: 1mg/kg/dose 3x/day; Dose Level 1/Treatment Period 2: 1mg/kg/dose 3x/day; Dose Level 2/Treatment Period 1: 3mg/kg/dose 3x/day; Dose Level 2/Treatment Period 2: 3mg/kg/dose 3x/day; Dose Level 3/Treatment Period 1: 10mg/kg/dose 3x/day; Dose Level 3/Treatment Period 2: 10mg/kg/dose 3x/day

Placebo Powder for Oral Solution DRUG

Matching Placebo Powder for Oral Solution

Dose Level 1/Treatment Period 1: Placebo 3x/day; Dose Level 1/Treatment Period 2: Placebo 3x/day; Dose Level 2/Treatment Period 1: Placebo 3x/day; Dose Level 2/Treatment Period 2: Placebo 3x/day; Dose Level 3/Treatment Period 1: Placebo 3x/day; Dose Level 3/Treatment Period 2: Placebo 3x/day

Eligibility Criteria

• Age: 3 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants (assent for participants older than 7 years of age) and/or their legal parent/guardian sign an Informed Consent Form (ICF) indicating that they understand the purpose of the procedures required for the study and are willing to participate
• When appropriate, pediatric participants, whose age, cognitive skills, reading abilities and maturity allow the understanding of the study protocol should provide written assent to participate.
• Male or female participants between the ages of 3 months to 17 years at the time of signing the informed consent or providing assent
• Have a confirmed diagnosis (genetic and/or histologic) of MVID
• Are able to ingest reconstituted Crofelemer Powder for Oral Solution either orally (PO) or through a previously-placed G-tube or GJ-Tube (not via J-Tube)
• Have, during the 8 weeks prior to baseline, a volume of PS that represents at least 50% (≥ 50%) of the participant's weekly hydration volume requirements
• If female participants have reached menarche, the participant (and caregiver) agree that the participant will remain abstinent or use two accepted methods of birth control during the course of the treatment period and for an additional 30 days following the last dose of study drug.
• Male participants (and caregiver) agree that the participant will remain abstinent or use contraception during the course of the treatment period and continue on for an additional 90 days following the last dose of study drug.

You may not qualify if:

• Within the last 4 weeks before study initiation, participants have:
• had significant changes to PS requirements (i.e., ± \> 20%)
• had a new requirement for diuretics
• had any infection requiring IV antibiotic administration
• had a documented active gastrointestinal infection
• initiated any new anti-diarrheal drug
• had an increase in ALT, AST, or total bilirubin that is ≥2 times the participant's usual laboratory values
• previously received an organ transplant
• any currently-diagnosed malignancy
• is pregnant or breastfeeding
• any investigator determined criteria for inability to participate in this study

Sponsors & Collaborators

• Napo Pharmaceuticals, Inc.: lead

Study Sites (3)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

UOS Gastroenterolgia e Riabilitazione nutrizionale Piazza Sant' Onofrio 4

Rome, Italy

NOT YET RECRUITING

Al Jalila Children's Hospital

Dubai, United Arab Emirates

RECRUITING

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MeSH Terms

Conditions

Microvillus inclusion disease; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Rare Diseases

Interventions

Solutions

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Lissette Jimenez, MD, MPH

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Pravin Chaturvedi, PhD

  Napo Pharmaceuticals, Inc.

  STUDY CHAIR

Central Study Contacts

Maha Dakhloul, BSc.Pharmacy

CONTACT

+96178967637; mdakhloul@ctifacts.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
• Masking Details: This is a randomized, double-blind, placebo-controlled, dose-escalating study with a placebo cross-over design within each participant at each dose level in this ultra-rare MVID participant population
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each dose level will include 2 4-week Treatment Periods for a total of 8 weeks. There will be 3 ascending dose levels for a total of 24 weeks of treatment with either crofelemer or placebo, with safety reviews between dose levels. Within the 24 weeks of treatment, each of crofelemer and placebo will have been administered at 3 ascending dose levels for 4 weeks each, totaling 12 weeks.

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: December 6, 2024
• Study Start: May 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: March 1, 2026
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); IT (1); AE (1)