Safety, Attenuation and Immunogenicity of GAP3KO Administered Via A Stephensi Mosquitoes

Study Overview
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Brief Summary
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Study designed to evaluate safety and tolerability of a genetically attenuated P. falciparum (GAP3KO) that arrests early in the liver stage of the parasite life cycle. Study will also confirm the attenuation of the GAP3KO parasites using peripheral blood smears. Secondary objectives are to evaluate the humoral immune responses to GAP3KO.

Detailed Description
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This single arm, open-label, phase 1 safety study is designed to evaluate the safety and tolerability of a genetically attenuated P. falciparum (GAP3KO) that arrests early in the liver stage of the parasite life cycle. The study will also confirm the attenuation of the GAP3KO parasites using peripheral blood smears. The secondary objectives of the study are to evaluate the humoral immune responses to GAP3KO. A total of 10 healthy, malaria-naïve adult subjects will be enrolled to receive GAP3KO via the bite of 150-200 GAP3K0-infected A. stephensi mosquitoes under controlled conditions. Subjects will be evaluated for safety, reactogenicity, and signs and symptoms of malaria to confirm attenuation for 28 days, including monitoring in a hotel setting 8-18 days post GAP 3KO administration.

Official Title
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Trial to Assess the Safety, Attenuation and Immunogenicity of Genetically-attenuated p52-/p36-/sap1- Plasmodium Falciparum Parasites (GAP3KO) Administered Via Infected Anopheles Stephensi Mosquitoes to Malaria-Naïve Adults

Conditions
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Malaria

Intervention / Treatment
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* Biological: GAP3KO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good general health No hematologic, hepatic, or renal disease Weight greater than 50 kg Assessment of Understanding completed and passed prior to enrollment Availability and reliable access to trial center Females must use two forms of pregnancy prevention Exclusion Criteria: Recent (within 6 months) or planned travel to malaria endemic area History of confirmed malaria diagnosis Anticipated use of the following: Investigational malaria vaccine at any time Malaria chemoprophylaxis within 6 months Chronic systemic immunosuppressive medications within 6 months Blood products or immunoglobulin within 120 days Systemic antibiotics with antimalarial effects within 30 days Investigational product or vaccine within 30 days Live vaccine within 28 days; killed vaccine within 14 days of GAP3KO Medications known to significantly interact with chloroquine or Malarone History of: Sickle cell trait or other hemoglobinopathies Splenectomy or functional asplenia Systemic anaphylaxis Severe allergic reaction to mosquito bites or malaria treatment drugs History of chronic or active neurologic disease Cardiac disease or stroke Clinically significant medical condition, abnormal lab results Clinically significant abnormal ECG Moderate or high risk for coronary heart disease Acute illness Pregnant or nursing female HIV, Hepatitis B, or Hepatitis C Psychiatric condition that precludes compliance with the protocol Suspected or known alcohol or drug abuse Staff with direct involvement in conduct of the study or GAP activities

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GAP3KO<br> | Biological: GAP3KO<br>* GAP3KO administered via the bite of 150-200 GAP3KO-infected A. stephensi mosquitoes under controlled conditions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by frequency of AEs, SAEs, and patent parasitemia via peripheral blood smear |  | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSP antibody titer |  | 28 days | 
| Percent inhibition of in vitro sporozoite |  | 28 days |