Clinical Trials Register

Summary
EudraCT Number:	2019-004958-29
Sponsor's Protocol Code Number:	CHUBX2019/25
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-06-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2019-004958-29

A.3

Full title of the trial

EFFECT OF POLYETHYLENE GLYCOL TREATMENT ON INTESTINAL INFLAMMATION ASSOCIATED WITH CYSTIC FIBROSIS IN CHILDREN

EFFET D’UN TRAITEMENT PAR POLYETHYLENE GLYCOL SUR L’INFLAMMATION INTESTINALE ASSOCIEE A LA MUCOVISCIDOSE CHEZ L’ENFANT

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Polyethylene glycol and intestinal inflammation in cystic fibrosis

Polyéthylène glycol et inflammation digestive dans la mucoviscidose

A.3.2

Name or abbreviated title of the trial where available

MUCOLAX

A.4.1

Sponsor's protocol code number

CHUBX2019/25

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	CHU de Bordeaux
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AOI 2019 CHU de Bordeaux
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CHU de Bordeaux
B.5.2	Functional name of contact point	Clinical Trials Manager
B.5.3	Address:
B.5.3.1	Street Address	12 rue Dubernat
B.5.3.2	Town/ city	Talence
B.5.3.4	Country	France
B.5.4	Telephone number	33557820877
B.5.5	Fax number	33556794926
B.5.6	E-mail	aurore.capelli@chu-bordeaux.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	FORLAX 4 g, poudre pour solution buvable en sachet FORLAX 10 g, poudre pour solution buvable en sachet-dose
D.2.1.1.2	Name of the Marketing Authorisation holder	IPSEN PHARMA
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for oral solution in sachet
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cystic fibrosis

Mucoviscidose

E.1.1.1

Medical condition in easily understood language

Cystic fibrosis

Mucoviscidose

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011762
E.1.2	Term	Cystic fibrosis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Study the impact of a 3-month polyethylene glycol treatment on intestinal inflammation associated with cystic fibrosis in children aged 4 to 18 years, as measured by the fecal calprotectin assay.

Evaluer chez l’enfant de 4 à 18 ans, l’efficacité d’un traitement de 3 mois par polyéthylène glycol sur l’inflammation intestinale associée à la mucoviscidose, évaluée par le dosage de la calprotectine fécale.

E.2.2

Secondary objectives of the trial

Study the impact of a 3-month treatment with polyethylene glycol:
- On digestive symptoms and quality of life,
- On the intestinal microbiota (bacterial and fungal)
Study the co-evolution of inflammation between the gut and lungs ("the gut-lung axis") during the 3 months of polyethylene glycol treatment.

Etudier l’efficacité à 3 mois d’un traitement par polyéthylène glycol :
- Sur les symptômes digestifs et la qualité de vie,
- Sur le microbiote intestinal (bactérien et fongique) et notamment le Microbial Dysbiosis Index1.
Etudier la co-évolution de l’inflammation entre l’intestin et les poumons (« l’axe intestin-poumon ») durant les 3 mois de traitement par polyéthylène glycol.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age ≥ 4 years old and <18 years old ;
- Patient with cystic fibrosis (sweat test > 60 mmol/l and/or molecular biology identifying mutations in the CFTR gene) with associated pancreatic insufficiency (fecal elastase <100 µg/g);
- With a rapid calprotectin assay result via the IBDoc test (Bühlmann®) superior or equal to 250 µg/g;
- Person affiliated or benefiting from a social security scheme;
- Free, informed and written consent signed by the holders of parental authority and the investigator before any examination required by the research and oral and/or written consent by the participant (depending on his/her age).

- Âge ≥ 4 ans et <18 ans ;
- Patient atteint de mucoviscidose (test de la sueur > 60 mmol/l et/ou biologie moléculaire identifiant des mutations du gène CFTR) avec insuffisance pancréatique associée (élastase fécale <100 µg/g) ;
- Présentant un résultat de dosage rapide de calprotectine via le test IBDoc (Bühlmann®) ≥ 250 µg/g ;
- Personne affiliée ou bénéficiaire d’un régime de sécurité sociale ;
- Consentement libre, éclairé et écrit signé par les titulaires de l’autorité parentale et l’investigateur avant tout examen nécessité par la recherche et assentiment oral et/ou écrit par le participant (en fonction de son âge).

E.4

Principal exclusion criteria

- Ongoing processing that can modulate the functionality of the CFTR (such as lumacaftor-ivacaftor protein therapy);
- Patient already on polyethylene glycol or other laxative within 3 months before the inclusion visit;
- Patient with diarrhea at inclusion (diarrhea will be defined as the presence of 3 or more stools / day in the 7 days prior to the inclusion visit);
- Acute viral or bacterial diarrhea in the month prior to the inclusion visit (associated with fever);
- Cure of oral or intravenous antibiotics or antifungals in the month preceding the collection of samples;
- Change in background treatment in the month prior to the inclusion visit (oral or inhaled corticosteroid therapy, azithromycin, inhaled antibiotic therapy, inhaled antifungal agent, proton pump inhibitors);
- Taking probiotics in the month before the inclusion visit;
- Transplanted patient (on immunosuppressants);
- Patient with IBD or celiac disease;
- Patient with digestive perforation or risk of digestive perforation;
- Patient with ileus or suspicion of intestinal obstruction, symptomatic stenosis;
- History of hypersensitivity to macrogol or any of the excipients
- Holders of parental authority enjoying judicial protection.

- Traitement en cours qui peut moduler la fonctionnalité du CFTR (thérapie protéique de type lumacaftor-ivacaftor) ;
- Patient déjà traité par polyéthylène glycol ou autre laxatif dans les 3 mois précédents la visite d’inclusion ;
- Patient présentant une diarrhée lors de l’inclusion (la diarrhée sera définie par la présence de 3 selles ou plus / jour dans les 7 jours précédents la visite d’inclusion) ;
- Diarrhée aigüe virale ou bactérienne dans le mois précédent la visite d’inclusion (associée à de la fièvre) ;
- Cure d’antibiotiques ou d’antifongiques oraux ou intraveineux dans le mois précédent le recueil des échantillons ;
- Modification du traitement de fond dans le mois précédent la visite d’inclusion (corticothérapie orale ou inhalée, azithromycine, antibiothérapie inhalée, antifongique inhalé, inhibiteurs de pompe à proton) ;
- Prise de probiotiques dans le mois précédent la visite d’inclusion ;
- Patient greffé (sous immunosuppresseurs) ;
- Patient atteint d’une Maladies Inflammatoires Chroniques de l’Intestin (MICI) ou d’une maladie cœliaque ;
- Patient ayant une perforation digestive ou risque de perforation digestive ;
- Patient ayant un iléus ou suspicion d’occlusion intestinale, une sténose symptomatique ;
- Antécédent d’hypersensibilité au macrogol ou à l’un des excipients
- Titulaires de l’autorité parentale bénéficiant d’une mesure de protection judiciaire.

E.5 End points

E.5.1

Primary end point(s)

proportion of patients with faecal calprotectin <250 µg / g measured by an ELISA test 3 months after initiation of treatment with polyethylene glycol, testifying to the absence of intestinal inflammation or slight inflammation.

proportion de patients avec une calprotectine fécale < 250 µg/g mesurée par un test ELISA à 3 mois de l’initiation du traitement par polyéthylène glycol, témoignant de l’absence d’inflammation intestinale ou d’une inflammation légère.

E.5.1.1

Timepoint(s) of evaluation of this end point

3 months after initiation of treatment with polyethylene glycol

à 3 mois de l’initiation du traitement par polyéthylène glycol

E.5.2

Secondary end point(s)

The evolution between the initiation of treatment (D0) and 3 months of treatment with polyethylene glycol (M3):
- Digestive symptoms and quality of life, assessed respectively by the validated questionnaire JenAwinen CF score and CFQ-R;
- The digestive inflammatory response, assessed by:
- The dosage of fecal calprotectin, interpreted as a quantitative variable (measured by an ELISA test),
- Analysis of the expression of genes involved in the inflammatory and pro-oncogenic response, using NanoString Technology and the nCounters® PanCancer Immune Profiling Panel and the production of the main cyto / chemokines produced by the digestive mucosa in the stool samples ..
- The composition of the bacterial and fungal intestinal microbiota, with:
- High-speed sequencing and phylogenetic assignment of the bacterial flora (on MiSeq, from Illumina®)
- High-speed sequencing of the region and phylogenetic affectation of the fungal flora (on MiSeq, from Illumina®)
- Confirmation by quantitative PCR of the species or genera whose relative abundance will be significantly modified
- Calculation of the MD-Index dysbiosis score for the intestinal microbiota.
- Pulmonary inflammation, assessed by the dosage of calprotectin in the sputum.

L’évolution entre l’initiation du traitement (J0) et 3 mois de traitement par polyéthylène glycol (M3) :
- Des symptômes digestifs et de la qualité de vie, évalués respectivement par le questionnaire validé JenAbdomen CF score et CFQ-R ;
- De la réponse inflammatoire digestive, évaluée par :
- Le dosage de la calprotectine fécale, interprété en tant que variable quantitative (mesurée par un test ELISA),
- L’analyse de l’expression des gènes impliqués dans la réponse inflammatoire et pro oncogénique, à l’aide de la Technologie NanoString et du panel nCounters® PanCancer Immune Profiling Panel et de la production des principales cyto/chimiokines produites par la muqueuse digestive dans les échantillons de selles..
- De la composition du microbiote intestinal bactérien et fongique, avec :
- Séquençage haut-débit et affectation phylogénétique de la flore bactérienne (sur MiSeq, de chez Illumina®)
- Séquençage haut-débit de la région et affectation phylogénétique de la flore fongique (sur MiSeq, de chez Illumina®)
- Confirmation par PCR quantitative des espèces ou genres dont l’abondance relative sera significativement modifiée
- Calcul du score de dysbiose MD-Index pour le microbiote intestinal.
- De l’inflammation pulmonaire, évaluée par le dosage de la calprotectine dans les crachats.

E.5.2.1

Timepoint(s) of evaluation of this end point

at the initiation of treatment (D0) and at 3 months of treatment with polyethylene glycol (M3):

à l’initiation du traitement (J0) et à 3 mois de traitement par polyéthylène glycol (M3)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Essai bicentrique, non comparatif, prospectif, de phase II selon un schéma de Fleming.

Bicentric, non-comparative, prospective, phase II trial according to a Fleming scheme.

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-04-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-30

P. End of Trial
P.	End of Trial Status	Ongoing

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