A Clinical Trial to Assess the Safety and Immunogenicity of New Malaria Vaccine Candidates ChAd63 Pfs25-IMX313 and MVA Pfs25-IMX313

Study Overview
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Brief Summary
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This is a clinical trial in which healthy volunteers will be administered one or two experimental malaria vaccines. ChAd Pfs-IMX313 will either be administered alone or with MVA Pfs25-IMX313 in a prime-boost regime. All vaccines will be administered intramuscularly. Group 1 will receive one dose of ChAd63 Pfs25-IMX313 at 5x10^9 vp. Group 2A will receive one dose of ChAd63 Pfs-IMX313 at 5x10^10 vp. Group 2B will receive one dose of ChAd63 Pfs-IMX313 at 5x10^10 vp and one dose of MVA Pfs25-IMX313 at 1x10^8 pfu eight weeks later. Group 2C will receive one dose of ChAd63 Pfs25-IMX313 at 5x10^10 vp and one dose of MVA Pfs25-IMX313 at 2x10^8 pfu eight weeks later. The study will assess the safety of the vaccinations, and the immune responses to the vaccination. Immune responses are measured by tests on blood samples. Healthy volunteers will be recruited in Oxford and Southampton, England.

Official Title
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A Phase Ia Clinical Trial to Assess the Safety, Immunogenicity and Ex-vivo Efficacy of New Plasmodium Falciparum Malaria Vaccine Candidates ChAd63 Pfs-IMX313 Alone and With MVA Pfs25-IMX313

Conditions
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Malaria

Intervention / Treatment
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* Biological: ChAd63 Pfs25-IMX313
* Biological: MVA Pfs25-IMX313


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The volunteer must satisfy all the following criteria to be eligible for the study: Healthy adults aged 18 to 50 years Able and willing (in the Investigator's opinion) to comply with all study requirements Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination Agreement to refrain from blood donation during the course of the study Provide written informed consent Exclusion Criteria: The volunteer may not enter the study if any of the following apply: Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed) History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products. Any history of anaphylaxis in relation to vaccination Pregnancy, lactation or willingness/intention to become pregnant during the study History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) History of serious psychiatric condition likely to affect participation in the study Any other serious chronic illness requiring hospital specialist supervision Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week Suspected or known injecting drug abuse in the 5 years preceding enrolment Seropositive for hepatitis B surface antigen (HBsAg) Seropositive for hepatitis C virus (antibodies to HCV)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>ChAd63 Pfs25-IMX313 (5x10^9 vp) | Biological: ChAd63 Pfs25-IMX313<br> <br> |
| Active Comparator: Group 2A<br>ChAd63 Pfs25-IMX313 (5x10^10 vp) | Biological: ChAd63 Pfs25-IMX313<br> <br> |
| Active Comparator: Group 2B<br>ChAd63 Pfs25-IMX313 (5x10^10) and MVA Pfs25-IMX313 (1x10^8 pfu) 8 weeks later | Biological: ChAd63 Pfs25-IMX313<br> <br> Biological: MVA Pfs25-IMX313<br> <br> |
| Active Comparator: Group 2C<br>ChAd63 Pfs25-IMX313 (5x10^10) and MVA Pfs25-IMX313 (2x10^8 pfu) 8 weeks later | Biological: ChAd63 Pfs25-IMX313<br> <br> Biological: MVA Pfs25-IMX313<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of ChAd63 Pfs25-IMX313 when administered to healthy volunteers alone, and with MVA Pfs25-IMX313 in a prime-boost regime. |  | 8 months | 
| Ex-vivo efficacy of ChAd63 Pfs25-IMX313 when administered to healthy volunteers alone, and with MVA Pfs25-IMX313 in a prime-boost regime. The functional activity of the vaccine induced antibodies will be tested using membrane-feeding assays. |  | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Vaccine, Immune Response