| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Use of the candidate MMRV vaccine for immunization of healthy children 12 - 14 months of age against measles, mumps, rubella and varicella). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Fever, rash and chickenpox |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To demonstrate the non-inferiority of GSK Biologicals’ MMRVR co-administered with HAV and PCV compared to ProQuad co-administered with HAV and PCV at Day 42 with respect to
- the seroresponse rate for antibodies to
-> varicella virus
-> measles virus and rubella virus
-> mumps virus
- the geometric mean concentration (GMC) for anti-bodies to
-> varicella virus
-> hepatitis A virus in a subset of subjects
-> S. pneumoniae serotypes (anti-PS) 4, 6B, 9V, 14, 18C, 19F and 23F in a subset of subjects
• To demonstrate the non-inferiority of GSK Biologicals’ MMRVF co-administered with HAV and PCV compared to ProQuad co-administered with HAV and PCV at Day 42 with respect to
- the seroresponse rate for antibodies to
-> varicella virus
-> measles virus and rubella virus
-> mumps virus
- GMC for antibodies to
-> varicella virus
-> hepatitis A virus in a subset of subjects
-> anti-PS serotypes 4, 6B, 9V, 14, 18C, 19F and 23F in a subset of subjects
|
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate GSK Biologicals MMRVR co-administered with HAV and PCV and ProQuad co-administered with HAV and PCV at Day 42 with respect to
- the concentrations/titers of antibodies (Abs) to mumps virus, measles virus and rubella virus
- the seroresponse rate of Abs to HAV in a subset of subjects
- the percentage of subjects with anti-PS antibody concentrations ≥ 0.05, ≥0.2, ≥0.5 and ≥1.0 µg/mL in a subset of subjects
• To evaluate GSK Biologicals MMRVF co-administered with HAV and PCV and ProQuad co-administered with HAV and PCV at Day 42 with respect to
- the concentrations/titers of Abs to mumps virus, measles virus and rubella virus
- the seroresponse rate of Abs to HAV in a subset of subjects
- the percentage of subjects with anti-PS antibody concentrations ≥ 0.05, ≥0.2, ≥0.5 and ≥1.0 µg/mL in a subset of subjects
• To assess safety and reactogenicity of GSK Biologicals MMRVR or MMRVF co-administered with HAV and PCV compared to ProQuad co-administered with HAV and PCV |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Subjects for whom the investigator believes their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
• Male or female between 12 and 14 months of age at the time of first vaccination.
• Written informed consent obtained from the parent/guardian of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Have previously received 3 doses of 7-valent pneumococcal conjugate vaccine within the first year of life. |
|
| E.4 | Principal exclusion criteria |
• Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Planned administration/administration of a vaccine not foreseen by the study protocol from 30 days prior to vaccination until 42 days after vaccination, except for influenza vaccine.
• Previous vaccination against measles, mumps, rubella and/or varicella.
• Previous vaccination against hepatitis A or receipt of a fourth dose of pneumococcal conjugate vaccine.
• History of measles, mumps, rubella and/or varicella/zoster diseases.
• Known exposure to measles, mumps, rubella and/or varicella/zoster within 30 days prior to the start of the study.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination, including human immunodeficiency virus (HIV) infection.
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
• Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Planned administration/administration of a vaccine not foreseen by the study protocol from 30 days prior to vaccination until 42 days after vaccination, except for influenza vaccine.
• Previous vaccination against measles, mumps, rubella and/or varicella.
• Previous vaccination against hepatitis A or receipt of a fourth dose of pneumococcal conjugate vaccine.
• History of measles, mumps, rubella and/or varicel-la/zoster diseases.
• Known exposure to measles, mumps, rubella and/or varicella/zoster within 30 days prior to the start of the study.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination, including human immunodeficiency virus (HIV) infection.
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be ex-acerbated by any component of the vaccines.
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures. Un-complicated febrile convulsions are not an exclusion criterion.
• Residence in the same household as the following persons:
- New-born infants (0-4 weeks of age).
- Pregnant mother/women with a negative history of chickenpox disease and without recorded vaccination against chickenpox.
- Pregnant women at or beyond 28 weeks gestation regardless of varicella vaccination status or varicella disease history.
- Persons with known immunodeficiency.
• Acute disease at the time of enrolment. All vaccines can be administered to persons with a minor illness.
• Administration of polyclonal immunoglobulins and/or any blood products during the six months before entering the study or planned administration during the study period.
• Contra-indications to commercially available vaccines used in this study (Havrix, Prevnar, ProQuad).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1) Seroresponse for antibodies to varicella virus (VZV).
2) Concentration of antibodies to varicella virus.
3) Seroresponse for antibodies to mumps virus.
4) Seroresponse for antibodies to measles virus.
5) Seroresponse for antibodies to rubella virus.
6) Concentration of antibodies to hepatitis A virus.
7) Concentrations of antibodies to S. Pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| For all primary endpoints the timepoint of evaluation is at 42 days post vaccination. |
|
| E.5.2 | Secondary end point(s) |
1) Concentrations/titers of antibodies to mumps, measles and rubella viruses.
2) Vaccine Response to HAV.
3) Seropositivity rate for anti-PS antibody.
4) Occurrence of MMRV/ ProQuad injection site (local) solicited symptoms (pain, redness, swelling).
5) Occurrence of fever 38.0°C/100.4°F and > 39.5°C/103.1°F.
6) Occurrence of investigator-confirmed measles/rubella-like rash.
7) Occurrence of investigator-confirmed varicella-like rash.
8) Occurrence of investigator-confirmed parotid/salivary gland swelling.
9) Occurrence of unsolicited symptoms and medically-attended adverse events (excluding rash and parotid/salivary gland swelling).
10) Occurrence of new onset chronic illnesses (e.g. autoimmune disorders, asthma, type I diabetes and allergies) and conditions prompting ER (Emergency Room) visits.
11) Occurrence of serious adverse events (SAEs).
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- For endpoints 1, 2 and 3 at 42 days post vaccination.
- For endpoint 4 over 4 days post vaccination.
- For endpoint 5 over 15 days and over 43 days post vaccination.
- For endpoint 6, 7, 8 and 9 over 43 days post vaccination.
- For endpoint 10 and 11 approximately 6 months (Day 0-180). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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