Safety and Immunogenicity of Malaria Vaccines AdCh63 AMA1, MVA AMA1 and AMA1-C1/Alhydrogel®+/- CPG 7909

Study Overview
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Brief Summary
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This study aims to compare the safety and immunogenicity of AdCh63 AMA1 and MVA AMA1vaccine candidates administered alone and with adjuvants in various schedules. These vaccines consist of inactivated viruses which have been modified, so they cannot reproduce in humans, and also to include genetic material for malaria protein AMA1 which is expressed by the malaria parasite during blood stage infection. The vaccines are designed to stimulate an immune response to this malaria protein and thus provide protection against malaria infection. Adjuvants are a crucial component of modern vaccine regimens, increasing the immunogenicity and potency of protein vaccines. In this study we will assess whether virus vectored vaccines combined with protein in adjuvant AMA1-C1/Alhydrogel® and CPG 7909 adjuvant (emulsion containing TLR agonist) can induce stronger and more durable immune response.

Official Title
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A Phase Ia Study to Assess the Safety and Immunogenicity of Novel Schedules for Vaccination With the Candidate Malaria Vaccines; AdCh63 AMA1, MVA AMA1 & AMA1-C1/Alhydrogel® +/- CPG 7909

Conditions
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Malaria

Intervention / Treatment
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* Biological: AdCh63 AMA1 + MVA AMA1 + AMA1-C1/Alhydrogel®+ CPG 7909
* Biological: AdCh63 AMA1 + AMA1-C1/Alhydrogel®+ CPG 7909
* Biological: AdCh63 AMA1 + AMA1-C1/Alhydrogel®
* Biological: AdCh63 AMA1 AMA1-C1/Alhydrogel®+ CPG 7909
* Biological: AdCh63 AMA1 + MVA AMA1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Women only: Must practice continuous effective contraception for the duration of the study. Men only: Must use barrier contraception from day of any vaccination with CPG 7909, for 3 months. Agreement to refrain from blood donation during the course of the study and for 6 months after the end of their involvement in the study. Written informed consent Exclusion Criteria: History of clinical P. falciparum malaria Travel to a malaria endemic region during the study period or within the preceding six months with a significant risk of malaria exposure. Participation in another research study involving 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) Pregnancy, lactation or intention to become pregnant during the study History of allergic disease or reactions likely to be exacerbated by any component of the vaccine e.g. egg products, Kathon. History of clinically significant contact dermatitis. History of a known allergy to nickel (volunteers may be enrolled in group 5 if they have an allergy to nickel) Any history of anaphylaxis post vaccination. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). History of serious psychiatric condition that may 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). History or evidence of pre-existing autoimmune or antibody mediated disease or laboratory evidence of possible autoimmune disease, defined as anti-dsDNA ≥ 25 IU/mL or a positive antinuclear antibody (ANA) result at screening. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.

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 |
| --- | --- |
| Experimental: Group 1<br>AdCh63 AMA1 + MVA AMA1 + AMA1-C1/Alhydrogel®+ CPG 7909 | Biological: AdCh63 AMA1 + MVA AMA1 + AMA1-C1/Alhydrogel®+ CPG 7909<br>* 5x10^10 vp AdCh63 AMA1 Day 0, 1.25x10^8 pfu MVA AMA1 Day 56, AMA1-C1/Alhydrogel®+ CPG 7909 (80ug, 800ug, 564ug respectively) Day 112. IM injections<br>|
| Experimental: Group 2<br>AdCh63 AMA1 + AMA1-C1/Alhydrogel®+ CPG 7909 | Biological: AdCh63 AMA1 + AMA1-C1/Alhydrogel®+ CPG 7909<br>* 5x10^10 vp AdCh63 AMA1 Day 0,AMA1-C1/Alhydrogel®+ CPG 7909 (80ug, 800ug, 564ug respectively) Day 56. IM injections<br>|
| Experimental: Group 3<br>AdCh63 AMA1 + AMA1-C1/Alhydrogel® | Biological: AdCh63 AMA1 + AMA1-C1/Alhydrogel®<br>* 5x10^10 vp AdCh63 AMA1 Day 0, AMA1-C1/Alhydrogel® (80ug, 800ug respectively) Day 56. IM injections<br>|
| Experimental: Group 4<br>AdCh63 AMA1 AMA1-C1/Alhydrogel®+ CPG 7909 | Biological: AdCh63 AMA1 AMA1-C1/Alhydrogel®+ CPG 7909<br>* 5x10^10 vp AdCh63 AMA1 Day 0, AMA1-C1/Alhydrogel®+ CPG 7909 (80ug, 800ug, 564ug respectively) Day 112. IM injections<br>|
| Experimental: Group 5<br>AdCh63 AMA1 + MVA AMA1 | Biological: AdCh63 AMA1 + MVA AMA1<br>* 5x10^10 vp AdCh63 AMA1 Day 0, 1.25x10^8 pfu MVA AMA1 Day 112. IM injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of vaccination | To assess the safety of vaccination of healthy adults with AdCh63 AMA1, MVA AMA1 & AMA1-C1/Alhydrogel® +/- CPG 7909 administered in various schedules using actively and passively collected data on adverse events | Expected average of 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of vaccination | To assess the immunogenicity of vaccination of healthy adults with AdCh63 AMA1, MVA AMA1 & AMA1-C1/Alhydrogel® +/- CPG 7909 administered in various schedules by measuring T cell responses (IFN-γ ELISPOT, flow cytometry), B cell responses and antibody responses to AMA1. Further immunological assessments may be undertaken as necessary | Expected average of 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune response