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| Name | Class |
|---|---|
| European and Developing Countries Clinical Trials Partnership (EDCTP) | OTHER_GOV |
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Malaria transmission is falling in some parts of Africa as bed nets and anti-malarials become more widely available. However, transmission still persists and it appears that additional control measures are required. The leading malaria vaccine candidate in development is RTS,S which has efficacy against clinical malaria measured at 30-50% in the field. This partial protection might be enhanced by combination with other components. The other vaccination approach that has produced repeatable efficacy in humans is the use of viral vectors to induce T cell responses. Previous attempts with this vaccine approach have been effective in challenge studies in Oxford, but ineffective in the field, probably because of reduced immunogenicity.
Recently, studies in Oxford, Kenya and the Gambia have shown higher levels of immunogenicity by using a chimpanzee adenovirus (ChAd63) followed by an attenuated vaccinia virus (modified vaccinia Ankara) to deliver the pre-erythrocytic antigen, multiple epitope string with thrombospondin- related adhesion protein (ME-TRAP).
The increase in immunogenicity has lead to sterile protection in 3 out of 14 volunteers and partial protection in 5 out of 14 volunteers in challenge studies.
The investigators propose a Phase 2b study of 120 healthy adult men in Kenya. The investigators will assess the efficacy and further evaluate the immunogenicity and safety profile of the vaccine regimen. The investigators also intend to assess the correlates of efficacy and natural immunity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ChAd63 ME-TRAP and MVA ME-TRAP | Experimental | ChAd63 ME-TRAP / MVA ME-TRAP heterologous prime-boost immunisation |
|
| Rabies vaccine | Active Comparator | 2 x 2.5IU Verorab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation | Biological | ChAd63 ME-TRAP: 5 x 10^10vp MVA ME-TRAP: 2 x 10^8 pfu |
|
| Measure | Description | Time Frame |
|---|---|---|
| Vaccine Efficacy | The first episode of P.falciparum infection positive by PCR, for P.falciparum. | 18 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Vaccine immunogenicity | Measures of immunogenicity will include: Ex vivo ELISPOT responses to overlapping pools of ME - TRAP peptides. Cultured ELISPOT responses to overlapping pools of ME - TRAP peptides. ICS by flow cytometry for cell mediated immune responses ELISA for antibodies to malaria antigens | 24 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research - Coast | Kilifi | PO Box 230, 80108 | Kenya |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| D011819 | Rabies Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| Rabies vaccine | Biological | 2 x 2.5IU Verorab |
|
|
| Reactogenicity |
All solicited and unsolicited local and systemic vaccine- linked adverse events (AEs) including clinically significant laboratory abnormalities. |
| 24 weeks |
| D000079426 |
| Vector Borne Diseases |