| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Primary immunization against Plasmodium falciparum malaria). |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Parasitic Diseases [C03] |
| 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 describe the safety and reactogenicity of RTS,S/AS02D administered as 3 doses intramuscularly in the left thigh to infants at 10, 14 and 18 weeks of age, staggered with the administration of 3 doses of TETRActHib (vaccine against diphteria, tetanus, pertussis and Haemophilus influenzae type B) intramuscularly in the right thigh at 8, 12 and 16 weeks of age. |
|
| E.2.2 | Secondary objectives of the trial |
-To demonstrate the non-inferiority of antibody responses to hepatitis B, when administered as 3 doses of RTS,S/AS02D at 10, 14 and 18 weeks of age compared to the regimen of 3 doses of Engerix-B (hepatitis B vaccine) at the same ages.
-To describe antibody responses to the circumsporozoite (CS) antigen of the RTS,S/AS02D malaria candidate vaccine admin-istered as 3 doses intramuscularly in the left thigh to infants at 10, 14 and 18 weeks of age.
-To assess the efficacy of RTS,S/AS02D against infection (defined as Plasmodium. falciparum asexual parasitemia > 0) with P. falciparum malaria in infants immunized with RTS,S/AS02D as 3 doses at 10, 14 and 18 weeks of age. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•A male or female infant of between 6 and 12 weeks of age at the time of first vaccination.
•Written informed consent obtained from the parent(s) or guardian(s) of the subject.
•Free of obvious health problems as established by medical history and clinical examination before entering into the study.
•Born to a mother who is HBsAg negative.
•Born to a mother who is HIV negative.
•Born after a normal gestation period (between 36 and 42 weeks).
•Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study. |
|
| E.4 | Principal exclusion criteria |
•BCG administration within one week of proposed administration of a study vaccine.
•Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
•Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
•Any chronic drug therapy to be continued during the study period.
•Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Haemophilus influenzae type b or hepatitis B vaccines.
•Major congenital abnormality.
•Serious acute or chronic illness determined by clinical, physical examination and laboratory screening tests.
•Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination (no laboratory testing required).
•A family history of congenital or hereditary immunodeficiency.
•History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
•History of any neurological disorders or seizures.
•Maternal death.
•Moderate malnutrition at screening defined as weight for age Z-score less than -2; this corresponds to a weight of equal or less than 3.9 kg for 2 month old boys and equal or less than 3.6 kg for 2 month old girls.
•Hemoglobin < 80 g/L.
•Simultaneous participation in any other clinical trial.
•Same sex twin.
•Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Occurrence of serious adverse events (SAEs) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| From the time of first TETRActHib vaccination until months 6 post Dose 1. |
|
| E.5.2 | Secondary end point(s) |
1) Occurrence of unsolicited AEs
2) Occurrence of unsolicited AEs
3) Occurrence of unsolicted AEs
4) Occurrence of solicited general and local reactions
5) Occurrence of solicited general and local reactions
6) Anti-HBs antibody titers; difference between groups in percent seroprotection <10%
7) Anti-HBs antibody titers
8) Anti-CS antibody titers
9) Anti-diphteria, anti-tetanus, anti-pertussis (anti-BPT) and anti-PRP antibody titers measured by ELISA
10) The time to first malaria infection (first recording of infection of asexual stage falciparum parasites detected by the active de-tection of infection surveillance)
11) The asexual P. falciparum parasitemia (prevalence and density) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) After Dose 1, 2 and 3 of TETRActHib over a 14 day follow-up period
2) After Dose 1 and 2 of RTS,S/AS02D or Engerix-B over a 14 day follow-up period
3) After Dose 3 of RTS,S/AS02D or Engerix-B over a 30 day follow-up period
4) Over a 7 day follow-up period after TETRActHib
5) Over a 7 day follow-up period (day of vaccination and 6 subsequent days) after RTS,S/AS02D or Engerix-B
6) One month post Dose 3 of RTS,S/AS02D or Engerix-B
7) Prior to vaccination, 1 month post Dose 3 of RTS,S/AS02D or Engerix B
8) Prior to vaccination, 1 month post Dose 3, 3½ months post Dose 3 of RTS,S/AS02D or Engerix B
9) One month post Dose 3 of TETRActHib
10) Over a period starting 14 days after last vaccination with RTS,S/AS02D extending for 12 weeks
11) At 3½ months post Dose 3 (Month 6) |
|
| 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 | Yes |
| E.6.5 | Efficacy | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Safety, immunogenicity and efficacy |
|
| 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 | Yes |
| 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 | 2 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
| E.8.4 | Will this trial be conducted at multiple sites globally? | No |
| 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 | Yes |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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