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A Phase 1/2b Study of an Investigational Malaria Vaccination Strategy in 5-17 Month Old Infants and Children in Burkina Faso

Phase 1
Completed
Conditions
Malaria
Interventions
Biological: ChAd63 ME-TRAP and MVA ME-TRAP
Biological: Rabies vaccine
Registration Number
NCT01635647
Lead Sponsor
University of Oxford
Brief Summary

Prime boost vaccination with ChAd63 ME-TRAP followed eight weeks later with MVA ME-TRAP shows efficacy against malaria infection when tested in UK volunteers using sporozoite challenge experiments. It is a leading candidate vaccination strategy against malaria. In the field, Phase I studies have been conducted in adults in Kenya and The Gambia and children and infants in The Gambia. The vaccination strategy appears safe and well tolerated in these populations, and also shows impressive immunogenicity, not significantly different to that seen in the UK trials where efficacy was shown. In particular, recent data from The Gambia shows excellent safety and immunogenicity in infants in malaria endemic areas, who would be the ones to benefit most from such a vaccine against malaria. With this clinical development as background, the investigators now propose to evaluate efficacy against natural malaria infection in this important target group for an effective malaria vaccine, that is, 5-17 month infants and children living in malaria endemic areas. The proposed study area, Banfora, Burkina Faso, is highly endemic for Plasmodium falciparum malaria.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
730
Inclusion Criteria
  1. Healthy infant/child aged 5-17 months at the time of first study vaccination
  2. Informed consent of parent/guardian
  3. Infant / child and parent/guardian resident in the study area villages and anticipated to be available for vaccination and follow-up
Exclusion Criteria
  • Clinically significant skin disorder (psoriasis, contact dermatitis etc.), immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness.
  • Weight-for-age Z score of less than -3 or other clinical signs of malnutrition
  • History of allergic reaction, significant IgE-mediated event, or anaphylaxis to immunisation
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, Kathon, neomycin, beta-propiolactone.
  • Haemoglobin less than 8.0 g/dL, where judged to be clinically significant in the opinion of the investigator
  • Serum Creatinine concentration greater than 70 µmol/L, where judged to be clinically significant in the opinion of the investigator
  • Serum ALT concentration greater than 45 U/L, where judged to be clinically significant in the opinion of the investigator
  • Blood transfusion within one month of enrolment
  • Previous vaccination with experimental malaria vaccines.
  • Administration of any other vaccine or immunoglobulin less than one week before vaccination with any study vaccine.
  • Current participation in another clinical trial, or within 12 weeks of this study.
  • Any other finding which in the opinion of the investigators would increase the risk of an adverse outcome from participation in the trial or result in incomplete or poor quality data
  • Known maternal HIV infection (No testing will be done by the study team)
  • Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior recruitment. (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ChAd63 ME-TRAP and MVA ME-TRAPChAd63 ME-TRAP and MVA ME-TRAPChAd63 ME-TRAP / MVA ME-TRAP heterologous prime-boost immunisation
Rabies vaccineRabies vaccine2 x 2.5IU Verorab
Primary Outcome Measures
NameTimeMethod
Time to first episode of malaria meeting the primary case definition of clinical malaria episode6 months
Secondary Outcome Measures
NameTimeMethod
Duration of Protective efficacy against clinical malaria12 and 24 months

To assess the protective efficacy against clinical malaria of ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation, in 5-17 month old infants and children living in a malaria-endemic area, for 12 and 24\* months after the last vaccination.

Efficacy against asymptomatic P. falciparum infection6, 12 and 24 months

To assess the protective efficacy against asymptomatic P. falciparum infection of ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation, in 5-17 month old infants and children living in a malaria-endemic area, 6, 12 and 24\* months after the last vaccination

Immunogenicity Objectives24 months

* To assess the immunogenicity of ChAd63 ME-TRAP / MVA ME- TRAP heterologous prime-boost immunisation, in 5-17 month old infants and children living in a malaria-endemic area.

* To explore the immunologic correlates of protective efficacy of ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation, in 5-17 month old infants and children living in a malaria-endemic area.

Safety Objective6, 12 and 24 months

To assess the safety and reactogenicity of ChAd63 ME-TRAP / MVA ME-TRAP heterologous prime-boost immunisation, in 5-17 month old infants and children living in a malaria-endemic area, for 6, 12 and 24 months after the last vaccination.

Efficacy against secondary case definitions of clinical malaria6, 12 and 24 months

To assess the protective efficacy against secondary case definitions of clinical malaria of ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation, in 5-17 month old infants and children living in a malaria-endemic area, for 6, 12 and 24 months after the last vaccination

Trial Locations

Locations (1)

Centre for Clinical Vaccinology and 1. Centre National de Recherche et de Formation sur le Paludisme (CNRFP)/ Unité de Recherche Clinique de Banfora (URC-B)

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Ouagadougou, Burkina Faso

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