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 + TETRActHib (vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type B) co-administered as 3 doses intramuscularly in separate thighs to infants at 8, 12 and 16 weeks of age.
-To demonstrate the non-inferiority of antibody responses to antigens D (diphteria), T (tetanus), Pw (whole-cell pertussis), Hib (Haemophilus influenzae type B) and HBs (hepatitis B), when administered as 3 doses of RTS,S/AS02D + TETRActHib at 8, 12 and 16 weeks of age compared to a regimen of 3 doses of Engerix-B (hepatitis B vaccine) + TETRActHib at the same age when assessed at 1 month post Dose 3. |
|
E.2.2 | Secondary objectives of the trial |
-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 8, 12 and 16 weeks of age.
-To assess the efficacy of RTS,S/AS02D against infection with Plasmodium falciparum malaria (defined as P. falciparum asexual parasitemia > 0) in infants immunized with RTS,S/AS02D as 3 doses at 8, 12 and 16 weeks of age. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•A male or female infant between 6 and 10 weeks of age at the time of first vaccination.
•Written or oral, signed or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child.
•Subjects who the investigator believes that their par-ents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits).
•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 live within a 5 km radius of a dispensary. |
|
E.4 | Principal exclusion criteria |
•Acute disease at the time of enrollment.
•Serious acute or chronic illness determined by clinical or physical examination and laboratory screening tests.
•Laboratory screening tests out of range for haemoglobin, total white cell count, platelets, alanine aminotransferase and creatinine.
•Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Haemophilus influenzae type b or hepatitis B vaccines.
•BCG administration within one week of proposed administration of a study vaccine.
•Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s).
•Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•Administration of immunoglobulins, blood transfusions or other blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
•Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
•Previous participation in any other malaria vaccine trial.
•Simultaneous participation in any other clinical trial.
•Same sex twin.
•Maternal death.
•History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations.
•History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
•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) |
1) Occurrence of SAEs
2) Anti-hepatitis B surface antigen (anti-HBs) antibody titers; difference between groups in percent seroprotection < 10% AND anti-diphtheria antibody titers; difference between groups in percent seroprotection < 10% AND anti-tetanus antibody titers; difference between groups in percent seroprotection < 10% AND anti-polyribosyl-ribitol-phosphate (anti-PRP) antibody titers; difference between groups in percent seroprotection < 10% AND anti-pertussis (anti-BPT) antibody titers; GMT ratio between groups < 1.5. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) From the time of first vaccination until seven months post Dose 3 (Month 9).
2) One month post Dose 3.
|
|
E.5.2 | Secondary end point(s) |
1) Occurrence of unsolicited AEs after Dose 1, 2 and 3
2) Occurrence of solicited general and local reactions
3) Anti-HBs antibody titers
4) Anti-CS antibody titers
5) Anti-diphteria, anti-tetanus, anti-BPT and anti-PRP antibody titers measured by ELISA
6) The time to first malaria infection (first recording of infection of asexual stage falciparum parasites detected by the active de-tection of infection surveillance)
7) The asexual P. falciparum parasitemia (prevalence and density) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Over a 30-day follow-up period (day of vaccination and 29 sub-sequent days).
2) Over a 7-day follow-up period (day of vaccination and 6 subsequent days) after each vaccination.
3) Prior to vaccination, one month post Dose 2 and one month post Dose 3.
4) Prior to vaccination, one month post Dose 2, one month post Dose 3 and 7 months post Dose 3.
5) At screening and one month post Dose 3.
6) Over a period starting 14 days after Dose 3 and extending for 6 months.
7) At 7 months post Dose 3 (Month 9). |
|
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) | 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 | 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 |
Tanzania, United Republic of |
|
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |