Safety And Immunogenicity Of Novel Candidate Blood-Stage Malaria Vaccine P27A : Phase Ia/Ib

Study Overview
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Brief Summary
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P27A study is designed as a randomized phase Ia/Ib trial to evaluate the safety and immunogenicity of the blood stage candidate vaccine P27A against P. falciparum - P27A antigen and associated adjuvant (Alhydrogel or GLA-SE) - in malaria non exposed European volunteers(Switzerland; phase Ia) and malaria exposed African volunteers (Tanzania; phase Ib).

Official Title
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Safety And Immunogenicity Of Novel Candidate Blood-Stage Malaria Vaccine P27A With Alhydrogel® Or GLA-SE As Adjuvant: A Staggered, Antigen And Adjuvant Dose-Finding, Randomized, Multi-Centre Phase Ia/Ib Trial

Conditions
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Malaria

Intervention / Treatment
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* Biological: CH-Alum50
* Biological: CH-GLA2.5/50
* Biological: TZ Ver
* Biological: TZ Alum 50
* Biological: TZ GLA 2.5/10
* Biological: TZ GLA5/50
* Biological: TZ GLA2.5/50


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase Ia Inclusion criteria: Healthy volunteers aged 18-45 years General good health based on history and clinical examination Written informed consent obtained before any study procedure Female volunteers practicing contraception before and up to 13 weeks after the last immunisation Available to participate in follow-up for the duration of study (34 weeks) Reachable by phone during the whole study period Phase Ib inclusion criteria Healthy male volunteers aged 18-45 years General good health based on history and clinical examination Written informed consent obtained before any study procedure Available to participate in follow-up for the duration of study (34 weeks) Reachable by phone during the whole study period Having always lived in an area of low malaria transmission Exclusion Criteria: Phase Ia Exclusion criteria: Positive pregnancy test for females Actively breast feeding females Previous participation in any malaria vaccine trial Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers Any clinically significant laboratory abnormalities on screened blood samples beyond the normal range, as defined at the clinical trial site Enrolment in any other clinical trial during the whole trial period Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the 13 weeks preceding the screening visit or during the trial period except topical and inhaled steroids Volunteers unable to be closely followed for social, geographic or psychological reasons Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study Known hypersensitivity to any of the vaccine components (adjuvant or peptide) Vaccination or infusion of gammaglobulin from 4 weeks prior to the first vaccination and up to 6 weeks after the third vaccination Any history of malaria History of living in a malaria endemic area for more than five (5) years OR living in a malaria endemic area in early childhood. For practical purposes, all regions for which malaria chemoprophylaxis is advised by travel clinic are considered malaria endemic (cf. www.safetravel.ch). Known exposure to malaria in the previous six (6) months, defined as a visit to a malaria endemic region P27A ELISA positive OR parasite ELISA antibody positive AND Known exposure to malaria in a malaria endemic area P27A ELISA positive AND parasite ELISA antibody positive (with or without history of stay in a malaria endemic area) Intention to travel to malaria endemic countries during the study period Positive HIV, HBV or HCV tests Phase Ib exclusion criteria Previously participated in any malaria vaccine trial Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers Any clinically significant laboratory abnormalities on screened blood samples beyond the normal range, as defined at the clinical trial site Enrolment in any other clinical trial during the whole trial period Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the thirteen weeks preceding the screening visit or during the trial period except topical and inhaled steroids Volunteers unable to be closely followed for social, geographic or psychological reasons Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study Known hypersensitivity to any of the vaccine components (adjuvant or peptide) or to any of the control vaccine components Vaccination OR infusion of gammaglobulins from four (4) weeks prior to the first vaccination and up to six (6) weeks after the third vaccination Previous vaccination with the control vaccine Positive HIV, HCV test or HBVsAg positive Malaria parasite positivity by microscopy and/or RDT Having had a history of confirmed malaria episode in the last five year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alhydrogel CH-Alum50<br>intramuscular administration to Swiss volunteers of Alhydrogel and P27A antigen (50 microg) | Biological: CH-Alum50<br>* intramuscular administration to Swiss volunteers of Alhydrogel and P27A antigen (50 microg)<br>|
| Experimental: CH-GLA2.5/50<br>intramuscular administration to Swiss volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg) | Biological: CH-GLA2.5/50<br>* intramuscular administration to Swiss volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)<br>|
| Placebo Comparator: Control rabies vaccine Verorub TM TZ Ver<br>intramuscular administration of Rabies vaccine Verorub TM to in Phase IIb only to 8 Tanzanian volunteers in three injections | Biological: TZ Ver<br>* intramuscular administration of Rabies vaccine Verorub TM to in Phase IIb only to 8 Tanzanian volunteers in three injections<br>|
| Experimental: Alhydrogel TZ Alum 50<br>intramuscular administration to Tanzanian volunteers of Alhydrogel and P27A antigen (50 microg) | Biological: TZ Alum 50<br>* intramuscular administration to Tanzanian volunteers of Alhydrogel and P27A antigen (50 microg)<br>|
| Experimental: GLA-SE TZ GLA 2.5/10<br>intramuscular administration to Tanzanian volunteers of GLA-SE (2.5 microg ) together with the P27A antigen (10 microg) | Biological: TZ GLA 2.5/10<br>* intramuscular administration to Tanzanian volunteers of GLA-SE (2.5 microg ) together with the P27A antigen (10 microg)<br>|
| Experimental: GLA-SE TZ GLA5/50<br>intramuscular administration to Tanzanian volunteers of GLA-SE (5 microg) together with the P27A antigen (50 microg) | Biological: TZ GLA5/50<br>* intramuscular administration to Tanzanian volunteers of GLA-SE (5 microg) together with the P27A antigen (50 microg)<br>|
| Experimental: GLA-SE TZ GLA2.5/50<br>intramuscular administration to Tanzanian volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg) | Biological: TZ GLA2.5/50<br>* intramuscular administration to Tanzanian volunteers of GLA-SE (2.5microg) together with the P27A antigen (50 microg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of P27A with Alhydrogel or GLA-SE as adjuvant, in healthy European adults not previously exposed to the parasite Plasmodium falciparum and in healthy African adults previously exposed to the parasite | The safety profile will be assessed on the basis of immediate local and systemic reactogenicity measured from Day 0 to Day 28 after each vaccination | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the humoral immune response to the vaccine antigen | The humoral response to the vaccine antigen will be assessed in all volunteers by ELISA to measure the level of total antigen specific IgG. | 15 months | 
| Assessment of the cellular immune response to the vaccine antigen | The cellular immune response will be assessed in all volunteers by measuring the T cell proliferation and cytokine production following in vitro stimulation with the vaccine antigen (by Luminex on cell culture supernatant after in vitro stimulation of PBMC for 6 days with the P27A peptide). Proliferation of carboxyfluorescein diacetate succinimidyl ester (CFSE) loaded CD3+ CD4+ and CD3+CD8+ T cells will be assayed by using polychromatic flow cytometry. | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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plasmodium falciparum, long synthetic peptide, antibody, T cell, cytokine, vaccine, safety, phase 1