Safety study for the use of Rapamycin in children with familial adenomatous polyposis - RAPA-4-FAP

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2024-09-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

DGOS

External identifiers

EU CT number

2024-512079-11-00

ClinicalTrials.gov

NCT06308445

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To evaluate the safety profile of two doses of rapamycin in adolescents with Familial Adenomatous Polyposis.

Secondary objectives 2

1. To evaluate the effect of rapamycin on the number of polyps in the entire colon and by segments (rectum, left colon, transverse colon, and right colon) in adolescents with Familial Adenomatous Polyposis.
2. To evaluate the effect of rapamycin on the size of the largest polyp in each segment (rectum, left colon, transverse colon and right colon) in adolescents with Familial Adenomatous Polyposis.

Conditions and MedDRA coding

Familial adenomatous polyposis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Children aged 12 to 17 included at time of inclusion.
2. Patients with colonoscopy for diagnosis or follow-up of familial adenomatous polyposis. (The diagnosis of PAF is made when there is a family history of APC mutation in the child, or when several adenomatous polyps are found because of rectal discharge.)
3. Visualization of at least 5 polyps (> 2 mm).
4. Free and informed consent, signed by all holders of parental authority/legal representative, and assent of the minor patient.
5. Covered by or affiliated to a social security scheme.

Exclusion criteria 9

1. Inability to understand the nature and goals of the study and/or communication difficulties with the investigator.
2. Contraindication to performing a colonoscopy.
3. Advanced disease with high-grade dysplasia adenoma or even adenocarcinoma in situ that should required colectomy.
4. Signs of primary tuberculosis infection or respiratory infection
5. Any other medical or psychological condition deemed incompatible with the proper conduct of the study according to the investigator, in particular: History of cancer, Severe infections, immune deficiency, Family history of tuberculosis, Chronic pathology
6. Contraindications rapamycin use : Known hypersensitivity to rapamycin ; Unadvisable drug combinations (drugs interfering with CYP3A4 by inhibiting it (ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin) or activating it (rifampicin, rifabutin), live vaccines) ; Fructose intolerance, glucose-galactose malabsorption, sucrose isomaltase, lactase deficiency ; Liver disease with transaminases > 2.5 x normal ; Hematological involvement: anemia with Hb < 9 g/dL, leukopenia with leukocytes < 1000/mm3, platelets < 80,000/mm3 ; Hypercholesterolemia with LDL-cholesterol > 2 g/L ; Quantiferon positive
7. Participation in another clinical trial taking an investigational drug in the 3 months prior to the inclusion visit, or subject in an exclusion period for another clinical trial.
8. Patient with one or both parents under legal protection (guardianship, curatorship, safeguard of justice).
9. Pregnancy, breastfeeding, not agree to use effective contraception for the entire duration of the study and for 3 months after the end of the research.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Monitoring of adverse events (AEs) and serious adverse events (SAEs) for the duration of the experimental drug (rapamycin) and up to one month after discontinuation.

Secondary endpoints 2

1. Individual analysis of colonoscopies, blinded to patient identity and the timing of colonoscopy in relation to treatment (V1 or V12), enabling descriptive analysis of the number of polyps over 2 mm per segment (rectum, left colon, transverse colon, right colon) and the size of the largest polyp in each segment.
2. Analysis of colonoscopies in a matched manner for each patient (pre-treatment (V1) / post-treatment (V12)) in order to be able to carry out a more specific evaluation of the evolution of polyps after 6 months of rapamycin treatment.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie, Tsa 80035 Tsa 80035

City

Toulouse Cedex 9

Postcode

31059

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Pr MAS Emmanuel

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Caroline Peyrot

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 20 files

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

Application history

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