Clinical Trials Register

Summary
EudraCT Number:	2022-002715-38
Sponsor's Protocol Code Number:	APHP220775
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:	2023-02-24
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

2022-002715-38

A.3

Full title of the trial

Immunogenicity and reactogenicity of the Beta-variant recombinant protein booster vaccine (VidPrevtyn Beta, Sanofi) compared to a bivalent mRNA vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in adults previously vaccinated with at least 3 doses of COVID-19 mRNA vaccine:
A non-inferiority multicenter single-blinded, randomized trial

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

COVIBOOST 2

A.4.1

Sponsor's protocol code number

APHP220775

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 – Hôpitaux de Paris (AP-HP)
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	ANRS
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 – Hôpitaux de Paris (AP-HP)
B.5.2	Functional name of contact point	Christophe AUCAN
B.5.3	Address:
B.5.3.1	Street Address	1, avenue 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	331144841709
B.5.6	E-mail	christophe.aucan@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	Comirnaty Original/Omicron BA.4-5
D.2.1.1.2	Name of the Marketing Authorisation holder	BioNTech-Pfizer
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.3.1	Product name	Comirnaty
D.3.4	Pharmaceutical form	Dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	cOVID-19 mRNA vaccine (nucleoside-modified)
D.3.9.3	Other descriptive name	COMIRNATY
D.3.9.4	EV Substance Code	SUB218184
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	VidPrevtyn Beta, solution et émulsion pour émulsion injectable Vaccin contre la COVID-19 (recombinant, avec adjuvant) (strain D614)
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur
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.3.1	Product name	VidPrevTyn Béta (strain D614)
D.3.4	Pharmaceutical form	Dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SARS-CoV-2, B.1.351 variant, prefusion Spike delta TM protein, recombinant
D.3.9.3	Other descriptive name	VIDPREVTYN
D.3.9.4	EV Substance Code	SUB253544
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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

Adults who received at least 3 doses of mRNA Covid 19 vaccine (BioNTech-Pfizer and/or Moderna), the last dose received at least 6 months prior to the inclusion in the trial.

E.1.1.1

Medical condition in easily understood language

Adults who received at least 3 doses of mRNA Covid 19 vaccine (BioNTech-Pfizer and/or Moderna), the last dose received at least 6 months prior to the inclusion in the trial.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the immune response induced 28 days after a booster dose with the Beta-variant recombinant protein booster vaccine (VidPrevtyn® Beta, Sanofi) with that of a bivalent mRNA vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer), in adults previously vaccinated with at least 3 doses of COVID-19 mRNA vaccine, the last dose received at least 6 months prior the inclusion in the study.

E.2.2

Secondary objectives of the trial

1. To compare in each arm:
a) The early immune response at D15 after the boost.
b) The persistence of the immune response at M3, M6 and M12 after the boost.
2. To described in each arm the local and general reactogenicity of the booster dose.
3. To describe the factors and determinants of humoral response
4. To explore the breadth of T and B cellular immune response in the two groups and their relationship with the early ASC response (ancillary studies).
5. To describe Covid 19 incidence in each group
6. To constitute a biobank to evaluate seroprotection conferred by the 2 booster vaccines against future emergent SARS-CoV-2 variants.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female aged 18 years and over
2. Adult in a healthy condition or with a stable health status, determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health. Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment can be included at the discretion of the investigator.
3. For women of childbearing age: a negative highly sensitive pregnancy urinary test during the inclusion visit
4. Confirmed receipt of at least three doses of COVID-19 mRNA vaccine the last dose at least 6 months prior to study vaccine
5. Understands and agrees to comply with the study procedures
6. Written informed consent signed by both the participant and the investigator
7. Subject affiliated to the French Social Security System.

E.4

Principal exclusion criteria

1. Acute febrile infection (body temperature ≥ 38.0°C) within the previous 72 hours and/or presenting symptoms suggestive of COVID-19 within the previous 28 days
2. Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection < 3 months prior to the study vaccine dose.
3. Immunosuppressive therapy such as corticosteroids > 10 mg prednisone equivalent/day (excluding topical preparations and inhalers) within 3 months prior to inclusion or within 6 months for chemotherapies.
4. Treatment with immunoglobulins or other blood derivatives within 3 months prior to inclusion or scheduled administration of immunoglobulins or blood derivatives before the end of the study.
5. Any medical condition, such as cancer, that might impair the immune response.
6. Use of experimental immunoglobulins, experimental monoclonal antibodies or convalescent plasma is not permitted during the study.
7. Pregnancy or breastfeeding currently ongoing
8. History of severe adverse events following vaccine administration including anaphylactic reaction and associated symptoms such as rash, breathing problems, angioedema, and abdominal pain, or a history of allergic reaction that could be triggered by a component of the SARS-COV-2 vaccine at the time of the first vaccine injection
9. Any bleeding disorder considered as a contraindication to an intramuscular injection,
10. Participation in other interventional research involving humans within 4 weeks prior to the inclusion visit, or participation in any other vaccine trial excepted for those with mid or long term follow up when vaccination was made at least 4 weeks before the injection in the study. In this case no delay is required after the end of the study participation.
11. Subject under legal protection (e.g. guardianship)

E.5 End points

E.5.1

Primary end point(s)

There will be a coprimary endpoint:
Neutralizing antibody titers against the SARS-CoV-2 variant of most prominent public health interest according to pandemic evolution (among D614G, B.1.351, Omicron sub-variants BA.4-5, BQ1.1 and XBB or another recent variant) and against one of the targeted variant by the vaccines. The two variants will be specified in the statistical analysis plan before D28 data base lock.
Neutralizing antibody titers will be measured by a microneutralization technique 28 days after the booster dose.

E.5.1.1

Timepoint(s) of evaluation of this end point

28 days after the booster dose.

E.5.2

Secondary end point(s)

Humoral immune response:
1.1. Neutralizing antibody titers
a) Neutralizing antibody titers against SARS-CoV-2 D614G, and variants B.1.351, Omicron sub-variants BA.4-5, BQ1.1 and XBB (or another recent variant of prominent public health interest according to pandemic evolution), measured by a microneutralization technique, at D15, M3, M6 and M12 after the boost.
b) Seroresponse rate in each group. Seroresponse is defined as a 10 fold or greater rise in serum neutralization titer at each follow-up time (D15, D28, M3, M6 and M12) relative to D0.
1.2. ELISA:
Anti-Spike IgG levels expressed as BAU/mL, according to WHO recommendations, at D0, D15, D28, M3, M6 and M12 after boost.
1. 3. LUMINEX:
a) Antibodies to CTD domain of the SARS-CoV-2 N protein to detect recent natural infections at D0, D15, D28, M3, M6, M12 (quantitative arbitrary units).
b) Full length Spike protein expressed as BAU/mL)
c) Antibodies to RBD of Wuhan, B.1.1.7 (Alpha), B.1.617.2 (Delta), B.1.351 (Beta), Omicron BA.1/2/5, BQ1.1, XBB and others variants according to pandemic evolution at D0, D15, D28, M3, M6, M12 (quantitative arbitrary units).
2. Number and intensity of adverse events of any degree of
a) solicited local and systemic adverse events occurring up to day 7 after administration of the booster dose (assessed from the list of solicited adverse events);
b) unsolicited adverses events up to 28 days after administration of the booster dose;
3. Factors of interest are age, gender, previous SARS-COV-2 infection, time interval between the last dose and the booster dose, and vaccine boost type
4. Cellular immune response:
a) ELISpot IFN-IL-2 CD4 and CD8 response at D0 and D15 (ancillary analysis) against D614, and variants B.1.351, Omicron BA.5, BQ1.1 and XXB
b) Repertoire analysis of Memory spike specific B cells and early ASC response.
5. Number of Covid 19 cases (symptomatic with PCR or Ag positive tests or asymptomatic with anti NP antibodies increase from D7 to M12)

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 12 month after the booster dose.

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

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

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:

150

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

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2023-02-24.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

236

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

2023-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-03-20

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

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