A Phase Ib Trial of MSP 3 LSP in 1-2 Year Old Children in Burkina Faso

The study is a single centre randomized controlled and blinded study (observer blind). It will be conducted at the CNRFP Vaccinology unit located in Balonghin. Children in the catchments area within the 1-2 years age group, whose parents consent will be screened to randomise 45 eligible participants. Two MSP 3 dose levels will be evaluated; 15µg and 30µg. The study will start with immunizing older children with the lowest dose observing safety parameters closely, then proceed to to the higher dose with a two week of observation apart.

Clinical, biological and immune response data gathered after vaccination with 15µg and 30µg MSP 3 LSP will be compared to:

• The children's baseline data before vaccinations, and
• The post vaccination data of children in the control group.

Randomization will ensure that the comparison groups are similar in relevant characteristics at baseline. The concealment of allocation before enrolment will further enforce the randomisation. Individuals who will make the assessment of the study end points will be completely blinded of the vaccine administered. This will ensure that there is no observer bias. Further, reporting or information bias will be minimised, because the recipients will also not be aware of which vaccine they have been administered. This is possible because the selected control vaccine has not been in routine use in this area, and has only now been recommended by the Ministry of Health. Cross over immunisation at the end of the trial will involve only those children who will received the study vaccine; they will be administered the control vaccine in the interest of public health benefits for them.

The schedule of vaccination at 0, 1 and 2 months has been adopted because it is suitable for the target group. The idea is to eventually deploy the vaccine through the expanded programme on immunisation should the vaccine become registered for public use. For the EPI age group, it is not only an efficient delivery mechanism, but they are also the most vulnerable group to malaria.

In brief, the groups will be allocated as follows:

• Group 1: 23 participants (15 receiving MSP-3 vaccine 15 µg and 8 receiving Hepatitis B vaccine).
• Group 2: 22 participants (15 receiving MSP-3 vaccine 30 µg and 7 receiving Hepatitis B vaccine)

Immunization schedule will be 0, 1, and 2 months for all cohorts and provisionally as following for each group:

Study days 0, 28 and 56 for group 1; and Study days 14, 42, 70 for group 2 Vaccinations of groups 1 and 2 will be staggered: immunization in group 2 will start 2 weeks after group 1. This interval may be extended if deemed necessary due to SAEs or other safety concerns.Randomization will be done for each group at the times of first vaccinations.Route of inoculation will be by subcutaneous injection into right or left deltoid (alternately).

Each child will be observed for at least 60 minutes after vaccination to evaluate and treat any acute adverse events (AEs). Study duration will be approximately 13 months per participant. There will be a seven (7) day follow-up period for solicited adverse events (day of vaccination plus 6 subsequent days); and twenty eight (28) day follow-up period for unsolicited adverse events (Vaccination day plus 27 subsequent days). The follow-up for serious adverse events (SAE's) will be for 12 months following the first dose of study vaccine (9 months after dose 3).

At the end of the follow-up period for unsolicited AEs (i.e., one month after the third dose), participants will be followed by field workers at home at monthly intervals to record SAEs. For data collection, conventional paper Case Report Forms (in triplicate copies) will be used.

An interim analysis is foreseen after day 84 of follow up. At this stage decision will be considered whether to proceed to a phase 2b study or not, and with which dosage of MSP 3, based on the safety and immunogenicity profile.