Assessing the safety, tolerability, and effectiveness of crofelemer in people with the intestinal disease Microvillus Inclusion Disease (MVID) through multiple doses of this new drug

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Napo Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Digestive System Diseases [C06]

Trial duration

3 Jun 2025 → ongoing

Decision date (initial)

2024-08-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy

To evaluate safety and tolerability of 3 ascending doses of Crofelemer Powder for Oral Solution, compared to placebo, when administered to participants with MVID receiving PS

Secondary objectives 5

1. To evaluate preliminary efficacy of 3 ascending doses of Crofelemer Powder for Oral Solution, compared to placebo, when administered to participants with MVID receiving PS with the following secondary objectives: • Reduction in loose/watery stool quantity (volume and/or frequency) and improvement in stool consistency
2. • Improvement in metabolic acidosis
3. • Decreased total parenteral support (PS; defined as the sum of TPN and IV fluid volume requirements
4. • Decreased volume requirement of individual PS components, TPN and/or supplemental IV fluid volume
5. • Decreased requirement for additive electrolytes in IV or TPN fluids

Conditions and MedDRA coding

Microvillous Inclusion Disease (MVID)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003296-PIP02-24

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participants (and/or their legal caregiver and/or participant assent for participants older than 7 years of age) sign an Informed Consent Form (ICF) indicating they understand the purpose of the procedures required for the study and are willing to participate.
2. 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.
3. Male or female participants between the ages of 3 months to 17 years at the time of signing the informed consent by their legal caregiver and/or participant assent for eligible participants
4. Have a confirmed diagnosis (genetic and/or histologic) of MVID
5. 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)
6. Have required, during the 8 weeks prior to baseline, an average weekly volume of PS that represents ≥ 50% of the participant’s average weekly hydration volume requirements
7. 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.
8. 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.

Exclusion criteria 11

1. 1. Within the last 4 weeks before study day -2 (day of study initiation), participants have: a. had significant changes to PS requirements (i.e., ± > 20%)
2. 5. any investigator determined criteria for inability to participate in this study
3. b. had a new requirement for diuretics
4. c. had any infection requiring IV antibiotic administration
5. d. had a documented active gastrointestinal infection
6. e. initiated any new anti-diarrheal drug
7. f. had an increase in ALT, AST, or total bilirubin that is ≥2 times the participant’s usual laboratory values within the past 3 months04. had a documented active gastrointestinal infection
8. 2. previously received an organ transplant
9. 3. any currently diagnosed malignancy
10. 4. is pregnant or breastfeeding
11. 6. Known hypersensitivity to any of the components of study drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Assessment of AEs, SAEs, laboratory evaluations, physical exam (including height, weight, BMI, and assessment of hydration status), and urine output

Secondary endpoints 9

1. Assessment of change from baseline, compared to placebo, within each dose level and over the 24 weeks of treatment in the following endpoints: • Average daily loose/watery stool volume during 24-hour stool collections every 2 weeks.
2. • Average daily loose/watery stool frequency during 24-hour stool collections every 2 weeks
3. • Average daily stool consistency using the 7point pediatric version of the Bristol Stool Form Scale during 24-hour stool collections every 2 weeks
4. • Daily stool electrolytes changes (Na+, K+, Cl-) at the end of dose level 3 (at 20 and 24 weeks)
5. • Average weekly acetate supplementation
6. • Average weekly PS volume requirements
7. • Average weekly TPN volume requirements
8. • Average weekly supplemental IV fluid volume requirements
9. • Average weekly supplemental electrolytes (Na+, K+, Cl-) in PS and, separately, in TPN and IV fluids

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Napo Pharmaceuticals Inc.

Sponsor organisation

Napo Pharmaceuticals Inc.

Address

200 Pine Street Suite 400

City

San Francisco

Postcode

94104-2704

Country

United States

Scientific contact point

Organisation

Napo Pharmaceuticals Inc.

Contact name

Napo Therapeutics Clinical Operations Lead

Public contact point

Organisation

Napo Pharmaceuticals Inc.

Contact name

Napo Therapeutics Clinical Operations Lead

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 13 files

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

Application history

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