Clinical Trials Register

Summary
EudraCT Number:	2019-000839-21
Sponsor's Protocol Code Number:	DREPADOL
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Not Authorised
Date on which this record was first entered in the EudraCT database:	2019-04-24
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

2019-000839-21

A.3

Full title of the trial

Evaluation of the efficacy and safety of aprepitant in the management of vaso-occlusive crisis in sickle cell children: randomized, single-center, randomized, phase IIb/III prospective study

Evaluation de l’efficacité et de la tolérance de l’aprépitant dans la prise en charge de la crise vaso-occlusive chez l’enfant drépanocytaire : étude prospective monocentrique randomisée, de phase IIb/III

A.3.1

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

Efficacy and safety of aprepitant for vaso-occlusive crisis in sickle cell child

Efficacité et sécurité de l’aprépitant dans la prise en charge de la crise vaso-occlusive chez l’enfant drépanocytaire

A.3.2

Name or abbreviated title of the trial where available

DREPADOL

A.4.1

Sponsor's protocol code number

DREPADOL

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	Centre Hospitalier Intercommunal de Créteil
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	Addmedica
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	Centre Hospitalier Intercommunal de Créteil
B.5.2	Functional name of contact point	PONDARRE
B.5.3	Address:
B.5.3.1	Street Address	40 avenue de Verdun
B.5.3.2	Town/ city	CRETEIL
B.5.3.3	Post code	94000
B.5.3.4	Country	France
B.5.4	Telephone number	33145175392
B.5.5	Fax number	33145175426
B.5.6	E-mail	corinne.pondarre@chicreteil.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	Emend 125 mg - 80 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B. V.
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	Capsule
D.3.4.1	Specific paediatric formulation	No
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.IMP: 2
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	Emend 125 mg powder
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B. V.
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	Capsule
D.3.4.1	Specific paediatric formulation	No
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

vaso-occlusive crisis for patients with sickle cell disease

crise vaso-occlusive pour des patients atteints de drépanocytose

E.1.1.1

Medical condition in easily understood language

pain crisis for patients with sickle cell disease

crise douloureuse pour des patients atteints de drépanocytose

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10040644
E.1.2	Term	Sickle cell disease
E.1.2	System Organ Class	100000004850

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

The main objective is to evaluate whether aprepitant administered on admission for VOC reduces the cumulative dose of morphine during hospitalization, compared to the control group.

E.2.2

Secondary objectives of the trial

1 / To evaluate the effectiveness of aprepitant, in comparison with a usual care

2 / To evaluate the effectiveness of aprepitant, on the improvement of the clinical parameters during hospitalization (body temperature, respiratory rate, heart rate, air saturation in O2)

3 / Evaluate the effectiveness of aprepitant on the improvement of the H48 biological parameters of admission (leukocyte count, neutrophils, platelets, CRP, markers of hemolysis (hemoglobin, reticulocytes, bilirubin, transaminases, LDH)

4 / To evaluate the efficacy of aprepitant in reducing plasma levels of substance P during the first 48 hours of the child's VOC (H0 and H48)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Child between 6 years (age of possible use of the self-controlled Morphine pump) and 17 years (≥6 years and ≤17 years)
- Any genotype of major sickle cell syndrome (SS, SβThal, SC, SDpunjab)
- Admission to pediatric emergencies for a CVO, excluding an acute splenic sequestration crisis; living at home for less than 48 hours
- Requiring analgesic treatment with Morphine (Pain score ≥ 7/10 on the scale of the faces or ≥ 10/15 on the EVENDOL scale, according to the PEDIADOL recommendations)
- Informed consent signed by parents
- Affiliation to the French social security

E.4

Principal exclusion criteria

- Children in the regular transfusion program and children who have received a hematopoietic stem cell transplant
- Child hospitalized at least 5 times for CVO in the 12 months preceding the inclusion (psychic problems making difficult the evaluation of the pain)
- Child who has already been included in the study during a previous CVO (each child participates in the study only once)
- CVO evolving for more than 48 hours before admission to emergency
- Seizure of acute splenic sequestration at admission
- Children with any other pathology resulting from a painful phenotype
- Child with major problems or other problems preventing the self-controlled administration of Morphine
- Pregnancy
- Severe hepatic or renal insufficiency
- Patient with current treatment: pimozide, terfenadine, astemizole, cisapride. ciclosporin, tacrolimus, sirolimus, everolimus, alfentanil, alkaloids derived from ergot of rye, fentanyl and quinidine
- Hypersensitivity to the active substance or to any of the excipients of Emend (including rare hereditary problems of fructose intolerance, glucose-galactose malabsorption syndrome or sucrase / isomaltase deficiency.)
- Ongoing participation in an interventional research RIPH1

E.5 End points

E.5.1

Primary end point(s)

Cumulative dose of morphine (in mg / kg) during hospitalization

E.5.1.1

Timepoint(s) of evaluation of this end point

During all hospitalization time

E.5.2

Secondary end point(s)

Comparison in the 2 groups of:
• Cumulative dose of morphine at H24, H48, H72 and every 24h until discharge (mg / kg)
• Duration of hospitalization (in days)
• Number of transfusion episodes
• Need to add analgesic treatment (MEOPA, NEFOPAM)
• Occurrence of Acute Thoracic Syndrome after admission
• Readmission within 15 days of release (rebound effect)
• STAI-A anxiety score (state anxiety) at admission, at H72 and the day of discharge from hospital for children ages 11 to 17
• STAI-B Anxiety Score (trait anxiety) on day of discharge from hospital and 1 month after admission for children aged 11 to 17
• R-CMAS anxiety score (trait anxiety) at admission, at H72, the day of discharge from hospital and at 1 month of admission
• Pain score measured by Faces Scale-Revised (FPS) every day from admission to discharge from hospital
• Maximum score of pain measured by the EVENDOL scale (range of hetero-evaluation between 1 and 15) every day from admission to discharge from hospital
• Occurrence of vomiting
• Occurrence of pruritus
• Maximum body temperature every day from admission to discharge from hospital
• Minimum oxygen saturation every day from admission to discharge from hospital
• Maximum respiratory rate every day from admission to discharge from hospital
• Maximum heart rate every day from admission to discharge from hospital
• Hb levels in g / dl at H0 and H48
• Reticulocyte levels in G / L at H0 and H48
• Leukocyte count / mm3 at H0 and H48
• Polynuclear neutrophil count / mm3 at H0 and H48
• Platelet count in G / L at H0 and H48
• CRP in mg / L at H0 and H48
• TGO, TGP at H0 and H48
• Bilirubin at H0 and H48
• LDH at H0 and H48
• Substance rate P at H0 and H48

E.5.2.1

Timepoint(s) of evaluation of this end point

at H24, H48, H72 and every 24h until discharge

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

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

Yes

E.8.2.3.1

Comparator description

standart care

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

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

Yes

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

Yes

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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

2019-06-17

Ethics Committee Opinion of the trial application

Not-Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-05-28

P. End of Trial
P.	End of Trial Status	Not Authorised

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