Clinical Trials Register

Summary
EudraCT Number:	2021-004550-33
Sponsor's Protocol Code Number:	APHP211184
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-09-16
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

2021-004550-33

A.3

Full title of the trial

Immunogenicity and reactogenicity following a booster dose of COVID-19 mRNA vaccine (Pfizer-BioNtech) and two adjuvanted sub-unit vaccines (SP/GSK) administered in adults who received 2 doses of Pfizer-BioNTech mRNA vaccine as a primary vaccination: A randomized, single-blinded multicenter clinical 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

A.4.1

Sponsor's protocol code number

APHP211184

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/ DRCI
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	Health ministery
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/DRCI
B.5.2	Functional name of contact point	Project manager
B.5.3	Address:
B.5.3.1	Street Address	1 avenue Calude 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	33140275009
B.5.6	E-mail	eunice.nubret@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, concentrate for dispersion for injection, COVID-19 mRNA Vaccine (nucleoside modified)
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer-BioNtech
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	Concentrate for 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	Comirnaty
D.3.9.3	Other descriptive name	COVID-19 mRNA vaccine (nucleoside-modified)
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	No
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	Vaccin SP/GSK CoV2 preS dTM-AS03 adjuvanted vaccine, strain D614
D.3.2	Product code	549
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CoV2 preS dTM-AS03 adjuvanted vaccine (D614)
D.3.9.2	Current sponsor code	Vaccin SP/GSK CoV2 preS dTM-AS03 adjuvanted vaccine, strain D614
D.3.9.3	Other descriptive name	Recombinant COVID19 Vaccine E
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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: 3
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	No
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	Vaccin SP/GSK, CoV2 preS dTM-AS03 adjuvanted vaccine, strain B.1.351
D.3.2	Product code	549
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CoV2 preS dTM-AS03 adjuvanted vaccine (B.1.351)
D.3.9.2	Current sponsor code	Vaccin SP/GSK, CoV2 preS dTM-AS03 adjuvanted vaccine, strain B.1.351
D.3.9.3	Other descriptive name	Recombinant COVID19 Vaccine C
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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

COVID-19

E.1.1.1

Medical condition in easily understood language

COVID-19

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 assess the immunogenicity of a booster dose of an adjuvanted subunit vaccine (SP vaccine) as between D614 or B.1.351 and a mRNA vaccine (Pfizer BioNTech) in adults who were primarily vaccinated with 2 doses of mRNA vaccine (Pfizer BioNTech) and received the 2nd dose of vaccine at least 6 months before the booster dose.

E.2.2

Secondary objectives of the trial

1. To compare the increase in neutralization antibody titers in participants with regard to the age group (18-64 years and 65 years or older)
2. To evaluate the local and general safety and tolerability of a booster dose of mRNA vaccine or adjuvanted subunit vaccine up to 28 days after administration;
3. To assess the humoral immune response by ELISA of a booster dose of mRNA vaccine or adjuvanted subunit vaccine at 28 days;
4. To assess the persistence of the immune response at 3 and 12 months after the booster dose of mRNA vaccine or adjuvanted subunit vaccine;
5. To evaluate the immunogenicity of the 3 vaccines on the D614, Alpha, Gamma and Delta viral variants;
6. To explore CD4 and CD8 cellular response induced by a booster dose of mRNA vaccine or adjuvanted subunit vaccine (sub-analysis)
7. To describe the associated factors and determinants of boost response in individuals previously vaccinated with 2 doses of mRNA vaccine (sub-analysis)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥ 18 years
2. Adult in a healthy condition or with a stable health status if pre-existing medical history. Stable health status is defined as an existing disease that has not required a significant change in treatment or hospitalization for worsening in the 3 months before enrollment, and for which neither a significant change in treatment or hospitalization for worsening is expected in the near future
3. For women of childbearing age: a negative highly sensitive pregnancy urinary test during the inclusion visit AND use of an effective contraceptive method at least 4 weeks prior to vaccination and until at least 12 weeks after the vaccination
4. Who has received 2 doses of mRNA vaccine (Pfizer-BioNTech) with an interval of 3 to 6 weeks
5. Second dose of mRNA vaccine (Pfizer-BioNTech) administered at least 6 months before the booster dose
6. Understands and agrees to comply with the study procedures
7. Written informed consent signed by both the participant and the investigator
8. 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 or having been in contact with an infected individual for the last 14 days before the inclusion visit;
2. Virologically documented history of COVID-19 (PCR or serology);
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. Known HIV, HCV or HBV infection;
6. Any medical condition, such as cancer, that might impair the immune response;
7. Use of experimental immunoglobulins, experimental monoclonal antibodies or convalescent plasma is not permitted during the study;
8. Pregnancy or breastfeeding currently ongoing;
9. 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;
10. Participant who has received BCG (tuberculosis) vaccine within the previous year
11. Has received a vaccine within 4 weeks prior to the boost injection or is scheduled to receive a registered vaccine 4 weeks after the boost injection
12. Any bleeding disorder considered as a contraindication to an intramuscular injection, previous phlebotomy or receipt of anticoagulants
13. Participation in other research involving humans (French classification Jardé 1 or Jardé 2) within 4 weeks prior to the inclusion visit, or participation in any other vaccine trial
14. Subject under legal protection (e.g. guardianship, tutorship)

E.5 End points

E.5.1

Primary end point(s)

Increased rate of at least 10 times between D0 and D28 after the booster dose in neutralizing antibody titers against SARS-CoV-2 D614 and B.1.351 viral strains, measured by a microneutralisation technique in each group.

E.5.1.1

Timepoint(s) of evaluation of this end point

Increased rate of at least 10 times between D0 and D28 after the booster dose

E.5.2

Secondary end point(s)

1. Rate of increase in neutralizing antibody titers against SARS-CoV-2 D614 and B.1.351 viral strains, measured by a microneutralisation technique between 0 and 28 days after the booster dose in each group.
2. Quantity and intensity of local and systemic events of any grade occurring up to 7 days after boost injection (assessed from the list of solicited adverse events); Quantity and intensity of unsolicited local and systemic events up to 28 days;
3. Anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels, expressed in BAU/ml, according to WHO recommendations D28 after the booster dose mRNA or adjuvanted subunit vaccine;
4. Difference in Anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels between D3 and D0 and between 12 months and D0;
5. Geometric means of antibody titers (against SARS-CoV-2 D614, Alpha, Gamma and Delta viral variants) and their evolution between D0, D28, M3 and M12;
6. ELISpot IFN CD4 and CD8 response at 28 days, 3 months and 12 months (sub-analysis)
7. Neutralizing antibody titers against D614, alpha, gamma, and delta variants at 28 days, 3 months and 12 months (sub-analysis)

E.5.2.1

Timepoint(s) of evaluation of this end point

Cf. Protocole

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

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

300

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

2021-11-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-09-07

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