Immunization of Human Volunteers With P. Vivax Irradiated Sporozoites

Study Overview
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Brief Summary
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It is possible to safely protect human volunteers immunized with P. vivax irradiated sporozoites from P. vivax challenge with live sporozoites.

Detailed Description
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Title: Phase 1 and Phase 2a Clinical Trial: Immunization of human volunteers with P. vivax irr-spz. (Short name: Irrad-SPZ) Population 27 healthy adult volunteers, males and non-pregnant females, between 18-45 years of age, who fulfill inclusion/exclusion criteria (described below) as determined by clinical history and serological tests. Approximately 20 parasitized blood-donor volunteers will be required to infected Anopheles mosquitoes which will be used to immunize volunteers with a total of 1000-1500 infected mosquitoes, during 8-10 months. Afterwards challenge to prove protection. Number of Sites: 2 Study Duration: 2 years. Subject Duration : Step1: 1-2 hours to blood donors; Step 2 and 3: 2 years to immunized volunteers Objectives Primary • To assess the safety and protective efficacy of P. vivax irradiated sporozoite vaccination. Secondary To determine the immune responses and duration elicited by the P. vivax challenge in human Fy(+) volunteers previously immunized with irr-spz, as compared with non-immunized human volunteers. To determine the immune responses and duration elicited by irr-spz immunization scheme in human Fy(+) volunteers; comparing it with the same immunization scheme with non irr-spz in Fy(-) participants, and also with controls exposed to the same mosquito bite scheme as that of immunization but using mosquitoes without parasite infection. To study new antigens potentially useful to induce pre-erythrocytic protection against P. vivax malaria infection

Official Title
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Phase 1 and Phase 2a Clinical Trial:Immunization of Human Volunteers With P. Vivax Irradiated Sporozoites

Conditions
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Malaria

Intervention / Treatment
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* Biological: Immunization with P. vivax irradiated sporozoites


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Healthy 18 to 45 years old man or non-pregnant women. To have the capacity to sign an informed consent in a free and voluntary way. Have an acceptable understanding of the clinical trial through the approval of a questionnaire regarding the information given in the consent process. Obligatory use of adequate contra-conceptive method from beginning of recruitment and screening time up to three months after last immunization Do not have chronic or acute diseases. These conditions will be determined by clinical history, physical exam and laboratory tests. To accept not traveling to malaria endemic areas during the clinical trial should To have telephone at home or mobile phone that permit permanent contact for follow up He (she) manifest that is willing to participated during both steps of the clinical trial. Exclusion Criteria: Volunteers with less than 18 old year or more than 45 old years. Pregnant and suckling women will be excluded. Pregnancy will be determined both by interview, and by serum B-subunit chorionic gonadotrophin testing. History of moderate or severe insect, or food allergies. G-6PD deficiency or any Hb genetic defect (for example; sickle cell disease) Previous malaria infection demonstrated by think smear, PCR or specific antimalarial antibodies. If the subject has previously participated in a malarial vaccine trial. Clinical record of allergies to drug or insect bites. Symptoms, signs or data from laboratory test that suggests to the physician any systemic disorder like renal, hepatic, cardiovascular, pulmonary, psychiatric disorders or other illnesses that could interfere with results of clinical trial or could compromise the health of the volunteer. To have antibodies against hepatitis C, VIH, or hepatitis B superficial antigen and/or hepatitis B core antibodies. To have any abnormality in the parameters assessed by blood laboratory tests. Base-line values will be established before initiation of the clinical trial. Presence or history of an auto-immune disease such as; Asthma, lupus, rheumatoid arthritis, Graves's disease, Hashimoto tyroiditis, and others. History of surgical removal of the spleen (splenectomy). Volunteer with medical treatment known to alter the immune system before 3 months to recruitment, such as; cortico-steroids, chemotherapeutic agents, fludarabine, cyclosporine, tacrolimus, mycophenolate mofetil, rapamycine, ATG, alemtuzumab. Alcoholism or drug abuse that may interfere with social relationship of individual.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fy(+)<br>14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites | Biological: Immunization with P. vivax irradiated sporozoites<br>* Anopheles albimanus mosquitoes will be infected by artificial membrane feeding using blood from P. vivax infected donors. Once mosquitoes are positive will be irradiated at 15000 cGy and kept in boxes until use. 14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites. Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites. Six Fy(-) volunteers will be exposed to infective mosquito bites. For the challenge both the immunized and control groups will be exposed to 3 ± 1 infective mosquito bites. Volunteers will be closely monitored post infection and will be treated with antimalarials.<br>* Other names: P. vivax irradiated sporozoites vaccine;|
| Active Comparator: Fy(+) control<br>Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites. | Biological: Immunization with P. vivax irradiated sporozoites<br>* Anopheles albimanus mosquitoes will be infected by artificial membrane feeding using blood from P. vivax infected donors. Once mosquitoes are positive will be irradiated at 15000 cGy and kept in boxes until use. 14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites. Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites. Six Fy(-) volunteers will be exposed to infective mosquito bites. For the challenge both the immunized and control groups will be exposed to 3 ± 1 infective mosquito bites. Volunteers will be closely monitored post infection and will be treated with antimalarials.<br>* Other names: P. vivax irradiated sporozoites vaccine;|
| Active Comparator: Fy(-)<br>Six Fy(-) volunteers will be exposed to infective mosquito bites. | Biological: Immunization with P. vivax irradiated sporozoites<br>* Anopheles albimanus mosquitoes will be infected by artificial membrane feeding using blood from P. vivax infected donors. Once mosquitoes are positive will be irradiated at 15000 cGy and kept in boxes until use. 14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites. Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites. Six Fy(-) volunteers will be exposed to infective mosquito bites. For the challenge both the immunized and control groups will be exposed to 3 ± 1 infective mosquito bites. Volunteers will be closely monitored post infection and will be treated with antimalarials.<br>* Other names: P. vivax irradiated sporozoites vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Three groups are considered to be intervened. Experimental, Control and Fy(-) groups. Comparison will be done between E and C groups for protective efficacy. For immune response tests E vs Fy(-),E vs Fy(-), and Fy(-) vs C, pairs will be compared. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects reporting any AEs, the occurrence of specifics AEs, and discontinuation due to AEs will be tabulated. Frequency of AEs will be cross-tabulated by group for each immunization session |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TBS Thick blood smear, RBC Red Blood Cells, GCP Good Clinical Practice, IFAT Indirect Immunofluorescence antibody test, MFA Membrane Feeding Assay, N Number (typically refers to subjects), SOP Standard Operating Procedure, P. Vivax, irradiated sporozoite vaccination.