Clinical Trials Register

Summary
EudraCT Number:	2022-002452-40
Sponsor's Protocol Code Number:	Td500056
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2023-03-08
Trial results	View 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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2022-002452-40

A.3

Full title of the trial

Immune Response to Pertussis after Vaccination with a Tdap-IPV Booster Vaccine in Children in the Republic of South Africa: Effect of Homologous and Heterologous Pertussis Vaccination Priming Background

A.3.1

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

Study to Evaluate the Immune Response After Booster Vaccination with Tdap-IPV Vaccine (Against Tetanus, Diphtheria, Pertussis and Poliomyelitis) in Children who Received Different Pertussis Primary Vaccine Regimens in Republic of South Africa

A.4.1

Sponsor's protocol code number

Td500056

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1223-5186

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	Sanofi Pasteur
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi Pasteur
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	Sanofi Pasteur
B.5.2	Functional name of contact point	Trial Transparency Team
B.5.3	Address:
B.5.3.1	Street Address	-
B.5.3.2	Town/ city	-
B.5.3.3	Post code	-
B.5.3.4	Country	France
B.5.6	E-mail	Contact-US@sanofi.com

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	Adacel Polio - Repevax - Adacel Quadra
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Suspension 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	DIPHTHERIA TOXOID
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	DIPHTHERIA TOXOID
D.3.9.4	EV Substance Code	SUB12489MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TETANUS TOXOID
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	TETANUS TOXOID
D.3.9.4	EV Substance Code	SUB12608MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PERTUSSIS TOXOID
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	PERTUSSIS TOXOID
D.3.9.4	EV Substance Code	SUB14817MIG
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	2.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FILAMENTOUS HAEMAGGLUTININ
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	FILAMENTOUS HAEMAGGLUTININ
D.3.9.4	EV Substance Code	SUB38509
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PERTUSSIS PERTACTIN
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	PERTUSSIS PERTACTIN
D.3.9.4	EV Substance Code	SUB20527
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	3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PERTUSSIS FIMBRIAL AGGLUTINOGENS (FIM) 2 AND 3
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	PERTUSSIS FIMBRIAL AGGLUTINOGENS (FIM) 2 AND 3
D.3.9.4	EV Substance Code	SUB25272
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POLIOVIRUS (INACTIVATED) TYPE 1 (MAHONEY STRAIN)
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	POLIOVIRUS (INACTIVATED) TYPE 1 (MAHONEY STRAIN)
D.3.9.4	EV Substance Code	SUB25292
D.3.10	Strength
D.3.10.1	Concentration unit	DAgU D antigen unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POLIOVIRUS (INACTIVATED) TYPE 2 (MEF-1 STRAIN)
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	POLIOVIRUS (INACTIVATED) TYPE 2 (MEF-1 STRAIN)
D.3.9.4	EV Substance Code	SUB25266
D.3.10	Strength
D.3.10.1	Concentration unit	DAgU D antigen unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POLIOVIRUS (INACTIVATED) TYPE 3 (SAUKETT STRAIN)
D.3.9.2	Current sponsor code	310
D.3.9.3	Other descriptive name	POLIOVIRUS (INACTIVATED) TYPE 3 (SAUKETT STRAIN)
D.3.9.4	EV Substance Code	SUB25264
D.3.10	Strength
D.3.10.1	Concentration unit	DAgU D antigen unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	32
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

Bacterial infections

E.1.1.1

Medical condition in easily understood language

Bacterial infections

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10069577
E.1.2	Term	Pertussis immunisation
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10054129
E.1.2	Term	Diphtheria immunisation
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10054131
E.1.2	Term	Tetanus immunisation
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10053386
E.1.2	Term	Poliomyelitis vaccine
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

- To describe the long-term humoral immune responses to pertussis, diphtheria, and tetanus after homologous and heterologous pertussis vaccine priming regimens
- To determine the effects of the priming regimen on humoral responses to booster vaccination with Tdap-IPV vaccine
- To describe the long-term cell-mediated immune responses to pertussis after homologous and heterologous pertussis vaccine priming regimens
- To determine the effects of the priming regimen on cell-mediated immune response to booster vaccination with Tdap-IPV vaccine

E.2.2

Secondary objectives of the trial

To describe the safety profile of Tdap-IPV vaccine in each group

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Born in 2007 to 2011 in the RSA
- Received primary pertussis vaccination and the toddler booster in the RSA
- Assent form has been signed and dated by the participant, and informed consent form (ICF) has been signed and dated by the parent(s) or another legal guardian and by an independent witness, if required by local regulations
- Participants and parent/legal guardian are able to attend all scheduled visits and to comply with all trial procedures
- Valid clinical record of primary vaccination with DTaP/DTwP vaccines immunization history from 2007 through 2011, either by hand-held (Road-to-Health Card) or immunization clinical records
- For Groups 6 and 7: children infected with perinatally acquired HIV infection currently under care who received either an all wP or all aP priming regimen
- For Groups 6 and 7: be on highly active antiretroviral therapy (HAART) therapy and have known CD4 cell counts > 200 cells/µL

E.4

Principal exclusion criteria

- Participation in the 4 weeks preceding the vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
- Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following the trial vaccination except for influenza
- Receipt of additional pertussis vaccination doses inconsistent with pertussis vaccination schedule in the RSA
- Previous confirmed diagnosis of pertussis disease
- Receipt of immune globulins, blood or blood-derived products in the past 3 months
- Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
- For Groups 1 to 5: known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- Known thrombocytopenia, as reported by the parent/ legal guardian or suspected thrombocytopenia contraindicating intramuscular vaccination in the Investigator’s opinion
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
- Participants with progressive neurological disorder, uncontrolled epilepsy, or progressive encephalopathy except if a treatment regimen has been established and the condition has stabilized
- Encephalopathy within 7 days of a previous dose of pertussis-containing vaccine
- Had contraindication to receipt of Adacel Quadra vaccine at the time of vaccination as defined in the Adacel Quadra vaccine Republic of South Africa (RSA) label
- Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective participants should not be included in the study until the condition has resolved or the febrile event has subsided (temporary contraindication)
- Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw
Note: Potential participants receiving standard HIV treatments such as antiretrovirals and/or antibiotic prophylaxis can be enrolled in the study. Their routine medications should be documented in the CRB.
- Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study

E.5 End points

E.5.1

Primary end point(s)

1- Geometric Mean Concentrations (GMCs) of anti-pertussis total immunoglobulin G (IgG): Total IgG anti-pertussis antibody concentrations against the following pertussis antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM)
2- GMCs of anti-diphtheria IgG: Total IgG anti-diphtheria antibody concentrations
3- GMCs of anti-tetanus toxoid IgG: Total IgG anti-tetanus antibody concentrations
4- in cell-mediated immunity (CMI) subset only: GMCs of anti-pertussis total immunoglubulin A (IgA) and of anti-heat-killed B pertussis (HK Bp) IgA : Total IgA anti-pertussis antibody concentrations against the following pertussis antigens: PT, FHA, PRN, FIM types 2 and 3, and heat-killed B. pertussis (HK Bp)
5- Geometric Mean (GM) of anti-pertussis IgG subclasses and of anti-HK Bp IgG subclasses : Anti-pertussis IgG subclasses (ie, IgG1, IgG2, IgG3, and IgG4) distribution against PT, FHA, PRN, FIM types 2 and 3, and HK Bp
6- GM of pertussis antigen-specific T cells: Absolute numbers (spot forming cells [SFC]/106 PBMCs) of pertussis antigen-specific (antigen pool and HK Bp) interferon (IFN)-ɣ, interleukin (IL)-17, IL-4 secreting cells

E.5.1.1

Timepoint(s) of evaluation of this end point

1 to 10: Day 0 (pre-vaccination) and Day 30 (post-vaccination)

E.5.2

Secondary end point(s)

1- Number of participants reporting immediate adverse events (AEs): Medically relevant unsolicited systemic AEs, including those related to the product administered
2- Number of participants reporting solicited injection site reactions and systemic reactions: Adverse reactions prelisted in the (electronic) case report book (CRB) Injection site reactions: pain, erythema, swelling Systemic reactions: fever, headache, malaise, myalgia
3- Number of participants reporting unsolicited AEs: AEs other than solicited reactions
4- Number of participants reporting serious adverse events (SAEs): SAEs, including adverse event of special interest (AESIs)

E.5.2.1

Timepoint(s) of evaluation of this end point

1- Within 30 minutes post-vaccination
2- Within 7 days post-vaccination
3- Within 30 days post-vaccination
4- Up to 37 days post-vaccination

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

Yes

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

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

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Information not present in EudraCT

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

South Africa

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.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

350

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:

220

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

130

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

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

350

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

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	South Africa

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