Administration of a new hexavalent vaccine (Hexavalent vaccine) with a meningococcal serogroup C conjugate vaccine in healthy infants during primary series immunisation and booster vaccination

• Register: EUCTR
• Last refreshed on: 7 December 2015
• Main ID: EUCTR2012-005547-24-FI
• Date of registration: 29/01/2013
• Prospective Registration: Yes
• Primary sponsor: Sanofi Pasteur MSD
• Public title: Administration of a new hexavalent vaccine (Hexavalent vaccine) with a meningococcal serogroup C conjugate vaccine in healthy infants during primary series immunisation and booster vaccination
• Scientific title: A phase III open-label randomised study to evaluate the immunogenicity and safety of the concomitant administration of a new Hexavalent DTaP-IPV-HepB-PRP-T combined vaccine (Hexavalent vaccine) given at 2, 3, and 4 months of age with a meningococcal serogroup C conjugate (MenC) vaccine given at 2 and 4 months of age
• Date of first enrolment: 07/03/2013
• Target sample size: 350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005547-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Finland

Contacts

• Name: Clinical Development Director
• Affiliation: Sanofi Pasteur MSD S.N.C.

• Name: Clinical Development Director
• Affiliation: Sanofi Pasteur MSD S.N.C.

Key inclusion & exclusion criteria

Inclusion criteria:
PRIMARY SERIES:
1. Healthy infant 46 to 74 days of age (both inclusive)
2. Born at full term of pregnancy (=37 weeks) and/or with a birth weight=2.5 kg
3. Informed consent signed by the subject's parent(s) or legal representative
4. Subject's parent(s) or legal representative able to comply with the study procedures
such as adherence to study visits and completion of the diary cards
5. Covered by health insurance

BOOSTER:
1. Infant who received 3 doses of the hexavalent vaccine in the Primary series
2. Healthy infant from 12 months of age
3. Informed consent signed by the subject's parent(s) or legal representative
Are the trial subjects under 18? yes
Number of subjects for this age range: 350
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
PRIMARY SERIES:
1. Participation at the time of study enrolment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
2. Receipt of any vaccine in the 4 weeks preceding each study vaccination or planned receipt of a vaccine in the 4 weeks following each study vaccine administration
3. Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b, meningococcal, pneumococcal, rotavirus infection
4. Know or suspected congenital, hereditary or acquired immunodeficiency or other immunosuppressive or immunodeficiency condition
5. History of seizures or encephalopathy
6. Known thrombocytopenia, as reported by the subject's parent or legal representative
7. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection
8. Chronic illness that, in the opinion of the investigators, is at a stage where it might interfere with trial conduct or completion
9. Known or suspected hypersensitivity to any of the study vaccines' active substance or excipients or history of a life-threatening reaction to a vaccine(s) containing the same substances as the study vaccines
10. Contraindication to any of the study vaccines as per their Summary of Product Characteristics
11. Known personal or maternal history of hepatitis B (HBs Ag) or hepatitis C seropositivity
12. History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b or meningococcal serogroup C infection
13. Receipt of immune globulin, blood or blood-derived products since birth
14. Receipt of immunosuppressive therapy or other immune-modifying drugs, such as anticancer chemotherapy or radiation therapy since birth
15. Receipt of systemic corticosteroid therapy for more than 14 consecutive days since birth
16. Identified as a natural or adopted child of the investigator or employee with direct involvement in the current study.

BOOSTER:
1. Prior (in the last 4 weeks), current or planned participation in another clinical study investigating a vaccine, drug, medical device, or medical procedure during the entire duration of the Booster vaccination
2. Receipt of a flu vaccine in the 2 weeks preceding vaccination at Visit 5 or receipt of any vaccine in the 4 weeks preceding vaccination at Visit 5 or planned receipt of a vaccine in the 4 weeks following vaccination at Visit 5
3. Previous booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b, meningococcal, pneumococcal infections with either the trial vaccine or another vaccine
4. History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b or meningococcal serogroup A, C, W or Y infection(s) confirmed either clinically, serologically, or microbiologically
5. Known or suspected hypersensitivity to any of the active substance or excipients or trace residuals of the hexavalent vaccine or the meningococcal group ACWY conjugate vaccine, to any pertussis vaccine, history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines
6. Contraindication to the hexavalent vaccine or the meningococcal group ACWY conjugate vaccine, as per their Summary of Product Characteristics
7. Receipt of imm

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Healthy infants 46 to 74 days of age (both inclusive)
MedDRA version: 17.0 Level: LLT Classification code 10054187 Term: Polio immunization System Organ Class: 100000004865
MedDRA version: 17.0 Level: LLT Classification code 10069543 Term: Hemophilus influenzae type b immunization System Organ Class: 100000004865
MedDRA version: 17.0 Level: LLT Classification code 10069593 Term: Pertussis immunization System Organ Class: 100000004865
MedDRA version: 17.0 Level: LLT Classification code 10054181 Term: Hepatitis B immunization System Organ Class: 100000004865
MedDRA version: 17.0 Level: LLT Classification code 10054180 Term: Diphtheria immunization System Organ Class: 100000004865
MedDRA version: 17.0 Level: LLT Classification code 10054183 Term: Tetanus immunization System Organ Class: 100000004865

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Trade Name: Hexyon
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: DIPHTHERIA TOXOID
Current Sponsor code: D
Other descriptive name: DIPHTHERIA TOXOID
Concentration unit: IU international unit(s)
Concentration type: not less then
Concentration number: 20-
INN or Proposed INN: TETANUS TOXOID
Current Sponsor code: T
Other descriptive name: TETANUS TOXOID
Concentration unit: IU international unit(s)
Concentration type: not less then
Concentration number: 40-
INN or Proposed INN: PERTUSSIS TOXOID
Current Sponsor code: PT
Other descriptive name: PERTUSSIS TOXOID
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: FILAMENTOUS HAEMAGGLUTININ
Current Sponsor code: FHA
Other descriptive name: PERTUSSIS FILAMENTOUS HAEMAGGLUTININ
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: INACTIVATED TYPE 1 POLIOVIRUS (MAHONEY)
Current Sponsor code: IPV
Other descriptive name: POLIOVIRUS (INACTIVATED) TYPE 1 (MAHONEY STRAIN) PRODUCED ON VERO CELLS
Concentration unit: DAgU D antigen unit(s)
Concentration type: equal
Concentration number: 40-
INN or Proposed INN: INACTIVATED TYPE 2 POLIOVIRUS (MEF-1)
Current Sponsor code: IPV
Other descriptive name: POLIOVIRUS (INACTIVATED) TYPE 2 (MEF-1 STRAIN) PRODUCED ON VERO CELLS
Concentration unit: DAgU D antigen unit(s)
Concentration type: equal
Concentration number: 8-
INN or Proposed INN: INACTIVATED TYPE 3 POLIOVIRUS (SAUKETT)
Current Sponsor code: IPV
Other descriptive name: POLIOVIRUS (INACTIVATED) TYPE 3 (SAUKETT STRAIN) PRODUCED ON VERO CELLS
Concentration unit: DAgU D antigen unit(s)
Concentration type: equal
Concentration number: 32-
INN or Proposed INN: HEPATITIS B SURFACE ANTIGEN
Current Sponsor code: Hep B
Other descriptive name: HEPATITIS B SURFACE ANTIGEN
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 10-
INN or Proposed INN: HAEMOPHILUS INFLUENSAE TYPE B POLYSACC

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: PRIMARY SERIES:
One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine.

BOOSTER:
One month after administration of hexavalent and/or MenACWY (at 13 months of age)

Main Objective: PRIMARY SERIES:
- To demonstrate that the concomitant administration of the hexavalent vaccine given at 2, 3 and 4 months of age with a meningococcal serogroup C conjugate (MenC) vaccine given at 2 and 4 months of age is non inferior to the administration of the hexavalent vaccine without a MenC vaccine concomitantly in term of seroprotection rate for hepatitis B one month after the third dose of the hexavalent vaccine.
- To demonstrate that the concomitant administration of a MenC vaccine given at 2 and 4 months of age with the hexavalent vaccine given at 2, 3 and 4 months of age induces an acceptable response for MenC in term of seroprotection rate (SPR) one month after the second dose of MenC.

BOOSTER:
To describe the immunogenicity of a booster dose of the hexavalent vaccine and of a meningococcal group ACWY conjugate vaccine either co-administered at 12 months of age or given separately.

Secondary Objective: PRIMARY SERIES:
Immunogenicity:
-To describe the antibody response to all the hexavalent vaccine antigens one month after the third dose of the hexavalent vaccine when given concomitantly or not to MenC vaccine.
-To describe the antibody response to MenC vaccine when a MenC vaccine is given concomitantly with the hexavalent vaccine, one month after the first and the second dose of MenC vaccine.
Safety:
-To describe the safety profile of the hexavalent vaccine after each and any injection when given concomitantly or not with a MenC vaccine.

BOOSTER:
Immunogenicity:
To describe the antibody (Ab) persistence at 12 months of age for the hexavalent valences following a 3-dose primary vaccination at 2, 3 and 4 months of age (prior to administration of a booster dose)
Safety:
To describe the safety of a booster dose of the hexavalent vaccine and of a meningococcal group ACWY conjugate (MenACWY) vaccine either co-administered at 12 months of age or given separately.

Primary end point(s): PRIMARY SERIES
Immunogenicity:
- Proportion of subjects with an anti-HBs concentration =10 mIU/mL
- Proportion of subjects with an anti-MenC titre =1:8 dil

BOOSTER:
Immunogenicity of hexavalent vaccine:
-Proportion of subjects with an anti-D concentration =0.1 IU/mL
-Proportion of subjects with an anti-D concentration =1.0 IU/mL
-Proportion of subjects with an anti-T concentration =0.1 IU/mL
-Proportion of subjects with an anti-T concentration =1.0 IU/mL
-Proportion of subjects with an anti-IPV1 titres =1:8 dil
-Proportion of subjects with an anti-IPV2 titres =1:8 dil
-Proportion of subjects with an anti-IPV3 titres =1:8 dil
-Proportion of subjects with an anti-HBs concentration =10 mIU/mL
-Proportion of subjects with an anti-HBs concentration =100 mIU/mL
-Proportion of subjects with an anti-PRP concentration =0.15 µg/mL
-Proportion of subjects with an anti-PRP concentration =1.0 µg/mL
-Booster response for pertussis antigens (PT and FHA) defined as follows:
- Post-booster Ab concentrations =4-fold rise if pre-booster Ab concentrations <4x LLOQ
- Post-booster Ab concentrations =2-fold rise if pre-booster Ab concentrations =4x LLOQ
-Anti-PT =4-fold Ab concentrations increase from pre- (Visit 5) to post-booster (Visit 6)
-Anti-FHA =4-fold Ab concentrations increase from pre- (Visit 5) to post-booster (Visit 6)
-Anti-D GMC
-Anti-T GMC
-Anti-IPV1 GMTs
-Anti-IPV2 GMTs
-Anti-IPV3 GMTs
-Anti-HBs GMC
-Anti-PRP GMC
-Anti-PT GMCs
-Anti-FHA GMCs

Immunogenicity of MenACWY vaccine:
-Proportion of subjects with an anti-MenA titre =1:8 dil
-Proportion of subjects with an anti-MenC titre =1:8 dil
-Proportion of subjects with an anti-MenW-135 titre =1:8 dil
-Proportion of subjects with an anti-MenY titre =1:8 dil
-Anti-MenA GMTs
-Anti-MenC GMTs
-Anti-MenW-135 GMTs
-Anti-MenY GMTs

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: PRIMARY SERIES:
Immunogenicity:
One month after dose 3 of Hexavalent vaccine

Proportion of subjects with an anti-MenC titre =1:8 dil: one month after dose 1 of MenC vaccines

Proportion of subjects with an anti-MenC titre =1:128 dil and Anti-MenC GMT: one month after dose 1 and one month after dose 2 of MenC vaccine.

Safety:
From Day 0 to Day 30 after each vaccination

BOOSTER:
Immunogenicity: Prior to administration of the hexavalent booster at 12 months of age

Safety: From Day 0 to Day 30 after vaccination

Secondary end point(s): PRIMARY SERIES:
Immunogenicity:
- Anti-HBs geometric mean concentrations (GMC)
- Proportion of subjects with an anti-PRP concentration =0.15 µg/mL
- Anti-PRP GMC
- Proportion of subjects with an anti-diphtheria (D) concentration =0.1 IU/mL
- Proportion of subjects with an anti-D concentration =0.01 IU/mL
- Anti-D geometric mean concentration (GMC)
- Proportion of subjects with an anti-tetanus (T) concentration =0.1 IU/mL
- Proportion of subjects with an anti-T concentration =0.01 IU/mL
- Anti-T GMC
- Proportion of subjects with an anti-inactivated poliovirus (IPV)1 titre =1:8 dil
- Proportion of subjects with an anti-IPV2 titre =1:8 dil
- Proportion of subjects with an anti-IPV3 titre =1:8 dil
- Anti-IPV1, anti-IPV2 and anti-IPV3 GMTs
- Proportion of subjects with an anti-PT vaccine response
- Proportion of subjects with anti-FHA vaccine response
- Anti-PT and anti-FHA GMCs
- Anti-PT and anti-FHA GMCRs
- Anti-PT and anti-FHA 4-fold increase

- Proportion of subjects with an anti-MenC titre =1:8 dil
- Proportion of subjects with an anti-MenC titre =1:128 dil

- Anti-MenC GMT

Safety:
- Incidence of solicited injection-sites reactions and solicited systemic adverse event.
- Incidence of unsolicited injection-site reactions, unsolicited systemic adverse events and all serious adverse events.

BOOSTER:
Immunogenicity, hexavalent vaccine:
-Proportion of subjects with an anti-D concentration =0.01 IU/mL
-Proportion of subjects with an anti-D concentration =0.1 IU/mL
-Proportion of subjects with an anti-T concentration =0.01 IU/mL
-Proportion of subjects with an anti-T concentration =0.1 IU/mL
-Proportion of subjects with an anti-IPV1 titre =1:8 dil
-Proportion of subjects with an anti-IPV2 titre =1:8 dil
-Proportion of subjects with an anti-IPV3 titre =1:8 dil
-Proportion of subjects with an anti-HBs concentration =10 mIU/mL
-Proportion of subjects with an anti-HBs concentration =100 mIU/mL
-Proportion of subjects with an anti-PRP concentration =0.15 µg/mL
-Proportion of subjects with an anti-PRP concentration =1.0 µg/mL
-Anti-PT and anti-FHA = LLOQ, 2x LLOQ
-Anti-PT and anti-FHA = LLOQ, 2x LLOQ
-Anti-D GMC
-Anti-T GMC
-Anti-IPV1 GMTs
-Anti-IPV2 GMTs
-Anti-IPV3 GMTs
-Anti-HBs GMC
-Anti-PRP GMC
-Anti-PT GMCs
-Anti-FHA GMCs

Secondary ID(s)

HXM01C

Source(s) of Monetary Support

Sanofi Pasteur

Sanofi Pasteur MSD-SNC