Immunogenicity and Safety Study of a Hexavalent DTaP-IPV-Hep B-PRP-T Combined Vaccine or Infanrix hexa™ Concomitantly Administered With 13-Valent Pneumococcal Conjugate Vaccine (PCV13), at 3, 5, 11 to 12 Months of Age in Healthy Infants in Europe

• Register: EUCTR
• Last refreshed on: 14 April 2014
• Main ID: EUCTR2012-001054-26-FI
• Date of registration: 27/06/2012
• Prospective Registration: Yes
• Primary sponsor: Sanofi Pasteur SA
• Public title: Immunogenicity and Safety Study of a Hexavalent DTaP-IPV-Hep B-PRP-T Combined Vaccine or Infanrix hexa™ Concomitantly Administered With 13-Valent Pneumococcal Conjugate Vaccine (PCV13), at 3, 5, 11 to 12 Months of Age in Healthy Infants in Europe
• Scientific title: Immunogenicity and Safety Study of a Hexavalent DTaP-IPV-Hep B-PRP-T Combined Vaccine or Infanrix hexa™ Concomitantly Administered With 13-Valent Pneumococcal Conjugate Vaccine (PCV13), at 3, 5, 11 to 12 Months of Age in Healthy Infants. Phase III, randomized, blind-observer, active-controlled, multi-center trial in 554 infants in Finland and Sweden.
• Date of first enrolment: 16/08/2012
• Target sample size: 554
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001054-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: blind-observer If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Finland, Sweden

Contacts

• Name: Director, Clinical Development
• Affiliation: Sanofi Pasteur SA

• Name: Director, Clinical Development
• Affiliation: Sanofi Pasteur SA

Key inclusion & exclusion criteria

Inclusion criteria:
An individual must fulfill all of the following criteria in order to be eligible for trial enrollment:
1) Aged 85 to 95 days on the day of the first study visit
2) Born at full term of pregnancy (= 37 weeks) and/or with a birth weight = 2.5 kg
3) Healthy subjects as established by medical history and clinical examination before entering into the study
4) Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative
5) Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures
6) Covered by health insurance
Are the trial subjects under 18? yes
Number of subjects for this age range: 554
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:
An individual fulfilling any of the following criteria is to be excluded from trial enrollment:
1) Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
2) Receipt of any vaccine in the 4 weeks preceding each trial vaccination or planned receipt of any vaccine in the 4 weeks following each trial vaccination (except rotavirus vaccination)
3) Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b or pneumococcal infections with another vaccine(s)
4) Receipt of immune globulins, blood or blood-derived products since birth
5) Known or suspected congenital, hereditary or acquired immunodeficiency or other immunosuppressive or immunodeficient condition
6) Receipt of immunosuppressive therapy or other immune-modifying drugs, such as anti-cancer chemotherapy or radiation therapy, since birth; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks since birth).
7) Known personal or maternal history of hepatitis B (HBsAg) or hepatitis C seropositivity
8) History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b, or pneumococcal infection(s), confirmed either clinically, serologically, or microbiologically
9) Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances
10) History of seizures or encephalopathy
11) Known thrombocytopenia, as reported by the parent/legally acceptable representative
12) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
13) Subjects in an emergency setting, or hospitalized involuntarily
14) Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
15) Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature = 38.0°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.
16) Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study


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

Health Condition(s) or Problem(s) studied

Prevention of infections caused by Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, poliovirus type 1, 2 and 3, prevention against invasive infections caused by Haemophilus influenzae type b and infection caused by hepatitis B virus
MedDRA version: 16.1 Level: LLT Classification code 10036897 Term: Prophylactic vaccination System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 16.1 Level: HLGT Classification code 10043413 Term: Therapeutic procedures and supportive care NEC System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 16.1 Level: PT Classification code 10021430 Term: Immunisation System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 16.1 Level: HLT Classification code 10021431 Term: Immunisations System Organ Class: 10042613 - Surgical and medical procedures

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Trade Name: Hexyon
Product Name: Hexyon
Product Code: DTaP-IPV-HepB-PRP-T
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Purified 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: Purified 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: PERTUSSIS 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: POLIOVIRUS (INACTIVATED) TYPE 1
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: POLIOVIRUS (INACTIVATED) TYPE 2
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: POLIOVIRUS (INACTIVATED) TYPE 3
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 (rDNA)
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

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Vaccination
All subjects will receive 3 doses of either Hexaxim or Infanrix hexa vaccines, co-administered with Prevenar 13 at 3, 5 and 11 to 12 months of age (D0 [V01], D60 [V02], and D240 to D270 [V04]).

Blood sampling
All subjects will provide a blood sample 1 month post-Dose 3 (V05; D270 to D300).

Primary end point(s): The following serological endpoints will be assessed 1-month after the 3rd dose (i.e., at V05 = Day 270 to Day 300) with seroprotection and vaccine response being respectively defined as:
Seroprotection for D, T, poliovirus 1, 2, and 3, Hep B, and PRP defined as follows:
• Anti-D and anti-T antibody (Ab) concentrations = 0.1 international units (IU)/mL
• Anti-poliovirus 1, 2, and 3 Ab titers = 8 (1/dil)
• Anti-Hep B Ab concentrations = 10 mIU/mL
• Anti-PRP Ab concentrations = 1 µg/mL
Vaccine response for PT and FHA defined as follows:
• Post-Dose 3 Ab concentrations = 4 x Lower Level Of Quantitation (LLOQ), if pre-Dose 1 Ab concentrations < 4 x LLOQ
• Post-Dose 3 Ab concentrations = pre-Dose 1 Ab concentrations, if pre-Dose 1 Ab concentrations = 4 x LLOQ

Main Objective: To demonstrate the non-inferiority of the Hexaxim vaccine to the licensed Infanrix hexa vaccine, both co-administered with Prevenar 13, in terms of seroprotection or vaccine response rates to all antigens contained in both investigational and control vaccines, 1 month after a 2+1-dose schedule.

Secondary Objective: Immunogenicity
• To describe in each group and in all subjects, the immunogenicity parameters before the first dose for PT and FHA antigens, and before and 1 month after the third dose for all the antigens contained in the hexavalent combined vaccines
• To describe in each group the immune responses to Prevenar 13 antigens in a subset of subjects, 1 month after a 2+1-dose schedule

Safety
To describe the safety profile after each and any injection in both vaccine groups.

Secondary Outcome(s)

Secondary end point(s): Immunogenicity
Pre-Dose 1 (D0, V01) :
• Ab concentrations for PT and FHA antigens
• Ab concentrations above a cut-off:
• Anti-PT Ab titers = LLOQ
• Anti-FHA Ab titers = LLOQ

Pre-Dose 3 (D240 to D270, V04):
• Ab concentrations/titers for each valence (except pneumococcal serotypes)
• Ab concentrations/titers above a cut off:
• Anti D Ab concentrations = 0.01 IU/mL and = 0.1 IU/mL
• Anti T Ab concentrations = 0.01 IU/mL and = 0.1 IU/mL
• Anti PT Ab concentrations = LLOQ and = 2 x LLOQ (4 ELISA units [EU]/mL)
• Anti FHA Ab concentrations = LLOQ and = 2 x LLOQ (4 EU/mL)
• Anti poliovirus 1, 2, and 3 titers = 8 (1/dil)
• Anti Hep B Ab concentrations = 10 mIU/mL and = 100 mIU/mL
• Anti PRP Ab concentrations = 0.15 µg/mL and = 1.0 µg/mL

Post-Dose 3 (D270 to D300, V05):
• Ab concentrations/titers for each valence
• Ab concentrations/titers above a cut-off :
• Anti-D Ab concentrations = 0.01 IU/mL and = 1.0 IU/mL
• Anti-T Ab concentrations = 0.01 IU/mL and = 1.0 IU/mL
• Anti-PT Ab concentrations = 2 x LLOQ (4 EU/mL)
• Anti-FHA Ab concentrations = 2 x LLOQ (4 EU/mL)
• Anti-Hep B Ab concentrations = 100 mIU/mL
• Anti-PRP Ab concentrations = 0.15 µg/mL
• Anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F concentrations = 0.35 µg/mL (in a subset of subjects only)
• Ab individual concentration ratios for anti-PT and FHA (post-Dose 3/pre-Dose 1 and post-Dose 3/pre-Dose 3).
• Ab individual concentration/titer ratios for D, T, poliovirus 1, 2, and 3, Hep B, PRP (post-Dose 3/pre-Dose 3)
• Seroconversion for anti PT and anti FHA, defined as anti PT and anti FHA = 4 fold Ab concentrations increase from pre-Dose 1 (V01) to post-Dose 3 (V05)
• Booster response for anti-PT and anti-FHA defined as follows:
• Post-Dose 3 Ab concentrations = 4-fold rise if pre-Dose 3 Ab concentrations < 4x LLOQ
• Post-Dose 3 Ab concentrations = 2-fold rise if pre-Dose 3 Ab concentrations = 4x LLOQ

Safety

Timepoint(s) of evaluation of this end point: Vaccination
All subjects will receive 3 doses of either Hexaxim or Infanrix hexa vaccines, co-administered with Prevenar 13 at 3, 5 and 11 to 12 months of age (D0 [V01], D60 [V02], and D240 to D270 [V04]).

Blood sampling
All subjects will provide a blood sample prior to Dose 1 (V01; D0), prior to Dose 3 (V04; D240 to D270), and 1 month post-Dose 3 (V05; D270 to D300).

Secondary ID(s)

2012-001054-26-SE

A3L38

Source(s) of Monetary Support

Sanofi Pasteur SA