Clinical Trials Register

Summary
EudraCT Number:	2019-000924-17
Sponsor's Protocol Code Number:	P170938J
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2019-06-19
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

2019-000924-17

A.3

Full title of the trial

Multicenter, randomized, phase III, trial assessing the immunogenicity and safety of three meningococal B vaccine strategies among patients with asplenia

Essai multicentrique, randomisé de phase III, évaluant l'immunogénicité et la tolérance de trois stratégies vaccinales contre le méningocoque B chez des patients présentant une asplénie

A.3.1

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

Multicenter, randomized, phase III, trial assessing the immunogenicity and safety of three meningococal B vaccine strategies among patients with asplenia

Essai multicentrique, randomisé de phase III, évaluant l'immunogénicité et la tolérance de trois stratégies vaccinales contre le méningocoque B chez des patients présentant une asplénie

A.3.2

Name or abbreviated title of the trial where available

SPLEMENGO

A.4.1

Sponsor's protocol code number

P170938J

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	ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
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	DGOS
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	ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
B.5.2	Functional name of contact point	DRCI Hôpital Saint-Louis
B.5.3	Address:
B.5.3.1	Street Address	1 av. Claude Vellefaux
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75010
B.5.3.4	Country	France
B.5.4	Telephone number	33144841712
B.5.5	Fax number	33144841701
B.5.6	E-mail	mandy.nizard@aphp.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	Bexsero®
D.2.1.1.2	Name of the Marketing Authorisation holder	GSK
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
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	Trumenba®
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
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

asplenic patients at risk for invasive meningococcal disease

Patients splénectomisés à risque d'infection à meningocoque B

E.1.1.1

Medical condition in easily understood language

asplenic patients

patients splénectomisés

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

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	10041642
E.1.2	Term	Splenectomy
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this trial is to assess immunogenicity one month after the completeness of three anti-meningococci B vaccine strategies (at M7 for all arms), in asplenic adults.

L'objectif principal de cet essai est d'évaluer l'immunogénicité un mois après l'achèvement de trois stratégies vaccinales antiméningocoques B (à M7 pour tous les bras) chez des adultes aspléniques.

E.2.2

Secondary objectives of the trial

1. To evaluate for each vaccine strategy, the immunogenicity one
month after the completeness of the vaccination scheme (M2/M7) (GMT,
proportion of responders to the threshold of 8) in asplenic adults.
2. To assess persistence and evolution of immune response until 48
months post 1st immunization for each vaccine strategy in asplenic
adults (at M12, M24, and M36 and M48).
3. To assess determinants of immune response to each vaccine strategy
in asplenic adults.
4. To evaluate, for each vaccine strategy, clinical and biological safety
of the vaccines in asplenic adults.
5. To assess safety and effectiveness of Bexsero® and Trumenba® in
asplenic adults older than 65 years of age

1. Evaluer pour chaque stratégie vaccinale l'immunogénicité un
mois après l'achèvement du schéma de vaccinal (M2 / M7)
(MGT, proportion de répondeurs au seuil de 8) chez l'adulte
asplénique.
2. Évaluer la persistance et l'évolution de la réponse
immunitaire jusqu'à 48 mois après la première immunisation
pour chaque stratégie vaccinale chez les adultes aspléniques (à M12, M24, M36 et M48).
3. Évaluer les déterminants de la réponse immunitaire à chaque
stratégie vaccinale chez l'adulte asplénique.
4. Évaluer, pour chaque stratégie vaccinale, l'innocuité clinique et
biologique des vaccins chez l'adulte asplénique.
5. Évaluer l'innocuité et l'efficacité de Bexsero® et de Trumenba®
chez l'adulte asplénique de plus de 65 ans.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, >=18 to <=75 years old.
2. Asplenic patient (for at least 2 weeks) with Howell Jolly bodies
visible on blood film and splenectomy confirmed by ultrasound.
3. Women of childbearing age must have an effective contraception
during the first 9 months of the study.
4. Participants must give written consent prior to any trial procedure.
5. Participants must be covered by social security regimen or
equivalent.
6. Participants will be followed during the 4 years from the inclusion
visit.

1. Homme ou femme,> = 18 à <= 75 ans.
2. Patiente asplénique (pendant au moins 2 semaines) avec les
corps de Howell Jolly visibles sur le film sanguin et la
splénectomie confirmée par échographie.
3. Les femmes en âge de procréer doivent avoir une
contraception efficace au cours des 9 premiers mois de l'étude.
4. Les participants doivent donner leur consentement écrit avant
toute procédure d'essai.
5. Les participants doivent être couverts par un régime de sécurité
sociale ou équivalent.
6. Les participants seront suivis pendant les 4 années suivant la
visite d'inclusion.

E.4

Principal exclusion criteria

1. History of meningococcal vaccination.
2. History of anaphylaxis post vaccination.
3. Known allergy to any components (active substances or excipients)
of both vaccines.
4. Patients who cannot stop antibiotics 7 to 10 days before blood
collection.
5. Participants who have received any another vaccines within 4 weeks
prior to immunization or who are planning to receive any vaccine within
the first 9 months of the study (excepted annual influenza vaccination
which is permitted 4 weeks before and after each vaccination visit of the
study and then allowed at any time during the study follow up).
6. Parenteral Ig within the 3 months prior to VS or planned during the
study.
7. Chemotherapy agents within 6 months prior M0 or planning to take
any during the study.
8. Steroids (> 10mg/day; > 14 days) within the month preceding M0 or
planning to take any during the study.
9. Any pathology or condition that may impair the immune response,
apart from splenectomy: immunosuppressive therapy in progress or in
the 6 months prior to inclusion, hematopoietic stem cells allo /autograft, primary immunodeficiency, nephrotic syndrome, evolutive
cancer, cirrhosis, known infection to HIV;
10. Thrombocytopenia or any coagulation disorder contra-indicating
intramuscularly injections.
11. Pregnancy, breastfeeding or positive pregnancy test up to 9 months
after inclusion.
12. Severe acute febrile illness within the week before inclusion.
13. Registration for any other clinical trial throughout the trial period
except observational study.

1. Antécédents de vaccination contre le méningocoque.
2. Antécédents d'anaphylaxie après la vaccination.
3. Allergie connue à l'un des composants (substances actives
ou excipients) des deux vaccins.
4. Les patients qui ne peuvent pas arrêter les antibiotiques 7 à
10 jours avant le prélèvement sanguin.
5. Participants ayant reçu un autre vaccin dans les 4 semaines
précédant l'immunisation ou prévoyant de le recevoir dans les
9 premiers mois de l'étude (sauf le vaccin annuel contre la
grippe autorisé 4 semaines avant et après chaque visite de
vaccination de l'étude puis autorisé à tout moment pendant le
suivi de l'étude).
6. Ig parentérale dans les 3 mois précédant la VS ou prévue au
cours de l'étude.
7. Agents de chimiothérapie dans les 6 mois précédant la
recherche M0 (1ere vaccination) ou prévoyant d'en recevoir
pendant l'étude.
8. Stéroïdes (> 10 mg / jour;> 14 jours) au cours du mois
précédant M0 (1ere vaccination) ou prévoyant d'en prendre
pendant l'étude.
9. Toute pathologie ou condition pouvant altérer la réponse
immunitaire, à l'exception de la splénectomie: traitement
immunosuppresseur en cours ou dans les 6 mois précédant
l'inclusion M0 (1ere vaccination), allogreffe/autogreffe de
cellules souches hématopoïétiques, immunodéficience
primaire, syndrome néphrotique, cancer évolutif, cirrhose,
infection connue au VIH.
10. Thrombocytopénie ou tout trouble de la coagulation contreindiquant
les injections intramusculaires.
11. Grossesse, allaitement ou test de grossesse positif jusqu'à 9
mois après l'inclusion.
12. Maladie fébrile aiguë sévère dans la semaine précédant
l'inclusion.
13. Participation à tout autre essai clinique pendant toute la

E.5 End points

E.5.1

Primary end point(s)

Proportion of responders defined as participants with seroconversion
(i.e. hSBA titer increases from <4 before vaccination to at least 4) or
with hSBA titer showing a 4-fold increase (if hSBA titer was at least 4
before vaccination) one month after the completeness of three antimeningococci
B vaccine strategies (at M7 for all arms) in asplenic adults.

Proportion de répondeurs définis comme participants avec
séroconversion (titre de hSBA augmente de < 4 avant le vaccin à
au moins 4) ou avec un titre de hSBA montrant une augmentation
de 4 fois (si le titre hSBA était d'au moins 4 avant la vaccination) un
mois après la complétude de trois stratégies de vaccin antiméningocoque B (à M7 pour tous les bras) chez des adultes aspléniques.

E.5.1.1

Timepoint(s) of evaluation of this end point

at Month 7

à la visite de M7

E.5.2

Secondary end point(s)

1. Immunogenicity at M2/M7, i.e. one month after the completeness of
each vaccine strategy:
- Serum bactericidal antibody (hSBA) Geometric Mean Titer (GMT).
- Proportion of responding participants using the conservative
threshold of 8.
- Proportion of participants achieving an hSBA titer equal to or greater
than the lower limit of quantification of the assay.
2. Persistence of immunogenicity at M12 M24, M36 and M48 for each
vaccine strategy
- Serum bactericidal antibody (hSBA), GMT.
- Proportion of responding participants using the conservative
threshold of 8.
- Proportion of participants achieving an SBA titre equal to or greater
than the lower limit of quantification of the assay.
3. Modeling of the determinants of immunogenicity: reason for
splenectomy, age, gender, immunosuppressive or immunomodulatory
agent.
4. Safety: Proportion of participant with an event (number, nature,
grade and time of occurrence)
- Local and/or systemic solicited reactions 7 days following each
vaccination.
- Any event or serious adverse event during the trial possibly or not
related to vaccine immunization.
5. To assess safety and effectiveness of Bexsero® and Trumenba® in
asplenic adults older than 65 years of age.

Immunogénicité à M2 / M7, soit un mois après la complétude
de chaque stratégie vaccinale :
- Anticorps bactéricides sériques (hSBA) moyenne
géométrique des titres (MGT).
- Proportion de participants ayant répondu utilisant le seuil
prudent de 8.
- Proportion de participants atteignant un titre de hSBA égal
Résumé du protocole « SPLEMENGO », version 1.0 du 03/12/2018 4/8
ou supérieur à la limite inférieure de quantification du
dosage.
2. Persistance d'immunogénicité à M12, M24, M36 et M48 pour
chaque stratégie vaccinale :
- Anticorps bactéricide sérique (hSBA), MGT
- Proportion de participants ayant répondu utilisant le seuil
prudent de 8.
- Proportion de participants obtenant un titre de SBA égal ou
supérieur à la limite inférieure de quantification du dosage.
3. Modélisation des déterminants de l'immunogénicité : motif de
la splénectomie, âge, sexe, agent immunosuppresseur ou
immunomodulateur.
4. Sécurité, Proportion de participants avec un événement
(nombre, nature, grade et heure de l'événement) :
- Réactions locales et / ou systémiques sollicitées 7 jours
après chaque vaccination.
- Tout événement ou événement indésirable grave au cours de l'essai, lié ou non à la vaccination.
5. Évaluer l'innocuité et l'efficacité de Bexsero® et de
Trumenba® chez l'adulte asplénique de plus de 65 ans.

E.5.2.1

Timepoint(s) of evaluation of this end point

at M2, M7, M12, M25, M36 and M48

à M2, M7, M12, M25, M36 et M48

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

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)

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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)

After the end of the trial, patients will be treated as part of their usual
clinical follow-up by their doctors

à la fin de l'étude les patients seront suivi et traités par leur médecin
traitent selon leur suivi habituel pour cette pathologie

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	I-REIVAC
G.4.3.4	Network Country	France

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-07-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-02

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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Orphan Designation Number:
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