Safety and Immunogenicity of ChAd63 RH5 and MVA RH5 in Adults, Young Children and Infants Living in Tanzania
Condition: Malaria,Falciparum
MeSH terms: Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a dose-escalation, age de-escalation randomised double-blind controlled Phase Ib
      trial to assess the safety, tolerability and immunogenicity of ChAd63-RH5 administered with
      MVA-RH5 in a heterologous prime-boost regimen. Adults (18-35 years), young children (1-6
      years) and infants (6-11 months) will be enrolled in the study. Safety data will be collected
      for each of the vaccination regimens. The humoral and cellular immune responses generated by
      each of these regimens will be assessed.
    

Detailed description: 
      -  Experimental design: Phase Ib, double blind, age de-escalation dose-escalation,
           randomized (2:1 ratio), controlled trial.

        -  Healthy adults (18-35 years), young children (1-6 years) and infants (6-11 months) will
           be screened; those determined to be eligible, based on the inclusion and exclusion
           criteria, will be enrolled in the study.

        -  Route of administration of ChAd63-RH5 (day 0) and MVA-RH5 (2 months): both vaccines will
           be administered by the intramuscular route to the left deltoid.

        -  Each participant will be observed for at least 1 hour after vaccination to evaluate and
           treat any acute adverse events (AEs).

        -  There will be 7-day follow-up period for solicited AEs post-vaccination: Day 0, 2 and 7
           evaluations will be carried out by the study clinician at the study centre and day 1, 3,
           4, 5 and 6 evaluations will be carried out by a trained community health worker in the
           participant's home, after each vaccination.

        -  There will be a 28-day (day of vaccination and 28 subsequent days) follow-up after each
           vaccine dose for reporting unsolicited symptoms.

        -  Serious adverse events (SAEs) will be recorded throughout the study period. Prior to
           vaccination, any SAEs due directly to study procedures will be captured. All SAEs will
           be captured beginning with the administration of the priming dose of ChAd63 RH5 and
           ending 4 months after the booster dose with MVA RH5.

        -  Antibodies to RH5_FL will be determined at baseline and 14, 28, 56, 63, 84, 112, 140 and
           168 days after ChAd63 RH5 in all participants.

        -  Cellular immune responses to RH5 will be evaluated at baseline and 14 (adults only), 28,
           56, 63, 84 and 168 days after ChAd63 RH5 in all participants.

        -  The duration of involvement in the study from enrolment will be approximately 6 months.
           The vaccination phase of the study takes 9 weeks and the post-vaccination follow-up
           lasts for 4 months after the last dose.
    

Intervention name(s): ChAd63 RH5; MVA RH5; Rabies Vaccine
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Vaccine; Vaccine; Vaccine
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: A Phase Ib age de-escalation dose-escalation randomised, double-blind, controlled study of the safety and immunogenicity of heterologous prime-boost with the candidate malaria vaccines ChAd63 RH5 and MVA RH5
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention