DTaP-IPV-Hib, with or without Hep B, booster vaccination in subjects aged 11 to 18 months previously vaccinated with a DTaP-IPV-Hib combination vaccine, with or without Hep B.

• Register: EUCTR
• Last refreshed on: 7 December 2015
• Main ID: EUCTR2012-001042-18-ES
• Date of registration: 22/12/2014
• Prospective Registration: Yes
• Primary sponsor: Sanofi Pasteur SA
• Public title: DTaP-IPV-Hib, with or without Hep B, booster vaccination in subjects aged 11 to 18 months previously vaccinated with a DTaP-IPV-Hib combination vaccine, with or without Hep B.
• Scientific title: Booster Effect and Safety of a DTaP-IPV-Hib Combined Vaccine, with or without Hep B, in Healthy Subjects 11 to 18 Months of Age Who Received a Hexavalent or Hexavalent/Pentavalent Combined Vaccine during the Primary Series.
• Date of first enrolment: 03/03/2015
• Target sample size: 795
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001042-18
• 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 (group 1 and group 2) and open-label (group 3) If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Czech Republic, Germany, Spain

Contacts

• Name: Unidad Estudios Clínicos
• Affiliation: Sanofi-Aventis, S.A.

• Name: Unidad Estudios Clínicos
• Affiliation: Sanofi-Aventis, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
An individual must fulfill all of the following criteria in order to be eligible for trial enrollment:
1) Infants/toddlers previously included in Study A3L39 who completed
the 3- dose primary series vaccination according to protocol
2) Groups 1 and 2 (Germany and the Czech Republic) aged 11 to 15 months on the day of the first study visit; Group 3 (Spain) aged 18 months on the day of the first study visit
3) Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by an independent witness if required by local regulations)
4) Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures
5) Covered by health insurance, if applicable
Are the trial subjects under 18? yes
Number of subjects for this age range: 795
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 4 weeks preceding the booster 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 out-of-study vaccines within the 2-week period prior to Visit 01 and within the 4-week period following the receipt of study vaccines or until all Visit 02 study procedures have been completed
3) Receipt of immune globulins, blood or blood-derived products in the last 3 months
4) Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 3 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
5) History of diphtheria, tetanus, pertussis, poliomyelitis, Hep B or Haemophilus influenzae type b and pneumococcal infections, confirmed either clinically, serologically, or microbiologically
6) 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
7) Known thrombocytopenia, as reported by the parent/legally acceptable representative
8) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
9) Subjects in an emergency setting, or hospitalized involuntarily
10) Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
11) 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.
12) Identified as a natural or adopted child of the investigator or employee with direct involvement in the proposed study
13) If any of the following events are known to have occurred in temporal relation to the receipt of a pertussis-containing vaccine, the decision to give further doses of pertussis-containing vaccines should be carefully considered:
? Encephalopathy
? Temperature of ? 40°C within 48 hours not due to another identifiable cause
? Collapse of shock-like state (hypotonic-hyporesponsive episode [HHE]) within 48 hours of vaccination
? Persistent, inconsolable crying lasting ? 3 hours, occurring within 48 hours if vaccination
? Convulsions with or without fever, occurring within 3 days of vaccination


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

Health Condition(s) or Problem(s) studied

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

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: 17.1 Level: LLT Classification code 10036897 Term: Prophylactic vaccination System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 17.1 Level: HLGT Classification code 10043413 Term: Therapeutic procedures and supportive care NEC System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 17.1 Level: PT Classification code 10021430 Term: Immunisation System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 17.1 Level: HLT Classification code 10021431 Term: Immunisations System Organ Class: 10042613 - Surgical and medical procedures

Intervention(s)

Trade Name: Prevenar 13
Product Name: Prevenar 13
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1 CONJUGATED TO CRM197
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.2-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3 CONJUGATED TO CRM197
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.2-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 4
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 4 CONJUGATED TO CRM197
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.2-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 5
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 5 CONJUGATED TO CRM197
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.2-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6A
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6A CONJUGATED TO CRM197
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.2-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6B
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6B CONJUGATED TO CRM197
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 4.4-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 7F
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 7F CONJUGATED TO CRM197
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.2-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 9V
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 9V CONJUGATED TO CRM197
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.2-
INN or Proposed INN: PNEUMOCOCC

Primary Outcome(s)

Primary end point(s): Immunogenicity
Ab Persistence
The following endpoints will be used to assess the Ab persistence (for all valences except PCV13 antigens) before the booster doses at Day 0 (D0) (Visit 1 [V01]) of the study vaccines:
? Ab concentrations/titers for each valence
? Ab concentrations/titers above a pre-determined 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-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 ?g/mL and ? 1.0 ?g/mL
? Anti-PT and anti-FHA Ab concentrations ? Lower Limit Of Quantitation (LLOQ)
Booster Effect:
The following endpoints will be used to assess the booster response for all antigens at D30 (V02):
? Ab concentrations/titers for each valence (including PCV13 for Groups 1 and 2 only)
? Ab concentrations/titers levels higher than a pre-determined cut-off:
? Anti-D Ab concentrations ? 0.01 IU/mL, ? 0.1 IU/mL, and ? 1.0 IU/mL
? Anti-T Ab concentrations ? 0.01 IU/mL, ? 0.1 IU/mL, and ? 1.0 IU/mL
? Anti-poliovirus 1, 2 and 3 titers ? 8 (1/dil)
? Anti-Hep B Ab concentrations ? 10 mIU/mL and ? 100 mIU/mL (Groups 1 and 2 only)
? Anti-PRP Ab concentrations ? 0.15 ?g/mL and ? 1.0 ?g/mL
? Anti-pneumococcal serotype 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F concentrations ? 0.35 ?g/mL (Groups 1 and 2 only)
? Individual concentration/titer ratio for each valence (D30 [V02]/D0 [V01]), except for PCV13 antigens
? Seroconversion for pertussis Ab (anti-PT and anti-FHA) defined as:
? Anti-PT and anti-FHA ? 4-fold Ab titers increase from D0 (V01) to D30 (V02)
? Booster response to pertussis (PT and FHA) defined as:
? Subjects whose pre-vaccination Ab concentrations are less than the
< LLOQ, will demonstrate the booster response if they have postvaccination
levels ? 4 x LLOQ
? Subjects whose pre-vaccination Ab concentrations are ? LLOQ but < 4 x LLOQ, will demonstrate the booster response if they have a 4-fold response (i.e. post- / pre-vaccination ? 4)
? Subjects whose pre-vaccination Ab concentrations are ? 4 x LLOQ, will demonstrate the booster response if they have a 2-fold response
(i.e. post- / pre-vaccination ? 2)
Safety
? Occurrence of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after booster vaccination
? Occurrence of solicited, i.e. pre-listed in the subject's diary and electronic case report form (eCRF), injection site and systemic reactions occurring up to 7 days after booster vaccination
? Occurrence of unsolicited (spontaneously reported) AEs up to 30 days after booster vaccination
? Occurrence of adverse events of special interest (AESIs) and SAEs, throughout the trial period
? Other endpoints recorded or derived will be described at the time of statistical analysis plan. Depending on the item, these could include: nature (MedDRA preferred term), time of onset, duration, number of days of occurrence, grade of severity, relationship to vaccine, action taken, whether the AE led to early termination from the study, seriousness, or outcome

Main Objective: Immunogenicity
Groups 1 and 2
? Assess the antibody persistence of DTaP-IPV-HB-Hib or Infanrix hexa following a 3-dose primary series at 2, 3, and 4 months of age (MoA) before the administration of a booster dose of either vaccine
? Describe the immunogenicity and booster effect of the DTaP-IPV-HBHib
or Infanrix hexa vaccine given as a booster dose at 11 to 15 MoA concomitantly with PCV13 (after a primary series with the same vaccine)
? To describe the immunogenicity of a booster dose of PCV13 given from
11 to 15 MoA
Group 3
? Assess the antibody persistence of all valences contained in the
vaccines administered in a mixed schedule following a 3-dose primary series at 2, 4, and 6 MoA before the administration of a booster dose of Pentavac
? Describe the immunogenicity and booster effect of Pentavac given at 18 MoA after the administration of a mixed schedule primary series combining a hexavalent and a pentavalent vaccine

To describe the safety profile for group 1, 2 and 3

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Blood sampling
All subjects will provide a pre-vaccination blood sample at D0 (V01) and a post-vaccination sample at D30 (V02).
Collection of safety data
Subjects' parents/legal representatives will record information about solicited reactions in a diary card (DC) from Days 0-7 post-vaccination, and will record information about unsolicited AEs from Days 0-30.
Solicited reactions will be collected for DTaP-IPV-HB-Hib, Infanrix hexa, Pentavac and PCV13 vaccines.
The SAEs will be recorded throughout the trial period.
Staff will contact subjects' parents/legal representative by telephone at 2-3 days and 8-10 days after vaccination to discuss any safety information.
Staff will review the Days 0-30 safety data with subjects' parents/legal
representatives at V02.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable

Secondary end point(s): Not applicable

Secondary ID(s)

2012-001042-18-DE

A3L40

Source(s) of Monetary Support

Sanofi Pasteur SA