Phase 1/2a Trial of Pf GAP p52-/p36- Sporozoite Malaria Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to assess safety and tolerability of escalating doses of a genetically attenuated parasite malaria vaccine (p52-/p36- GAP vaccine) in healthy malaria-naive adults. The study will also assess preliminary efficacy of p52-/p36- GAP vaccine following primary experimental challenge with P. falciparum sporozoites. Lastly, the study will assess immunogenicity of p52-/p36- GAP in malaria-naïve healthy adults and preliminary efficacy of p52-/p36- GAP vaccine following primary experimental re-challenge with P. falciparum sporozoites.

Official Title
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Phase 1/2a Trial to Assess the Safety, Immunogenicity and Efficacy of Genetically-attenuated Plasmodium Falciparum Parasites p52-/p36- (GAP) Vaccine, Administered by Bite of Infected Anopheles Mosquito to Malaria-naïve Adults Living in the United States.

Conditions
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Malaria

Intervention / Treatment
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* Biological: p52-/p36- GAP Vaccine
* Biological: p52-p36- GAP Vaccine
* Biological: p52-/p36- GAP Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or non-pregnant, non-lactating female 18 to 50 years of age (inclusive) at the time of enrollment Free of significant health problems as established by medical history, laboratory assessment and clinical examination before entering into the study Volunteers must have low cardiac risk factors according to the NHANES I criteria and a non-significant electrocardiogram (EKG) as determined by a expert consultant cardiologist Available to participate for duration of study Reproductive status: a female participant must: not be of reproductive potential: i.e. be surgically, medically or physiologically sterile, or if engages in sexual activity that could lead to pregnancy: agrees to consistently use contraception until 2 months after the last protocol visit. Contraception is defined as using 1 of the following methods: condoms (male or female) with or without a spermicide diaphragm or cervical cap with spermicide intrauterine device (IUD) hormonal contraception If the volunteer indicates he/she is active duty military (on the DCT sign-in page and intake form), approval from their supervisor through the Division Director using the Statement of Supervisor's Approval Form must be signed and on file prior to receipt of any test product Written informed consent must be obtained from the subject before screening procedures Prior to entry into this study, subjects must score at least 80% correct on a 10- question multiple-choice quiz that assesses their understanding of this study. Exclusion Criteria: Prior receipt of any investigational malaria vaccine Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period Administration of any vaccine within 30 days of first study vaccination Any past history of malaria Planned travel to malarious areas during the study period Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection A family history of congenital or hereditary immunodeficiency Moderate or high 5-year cardiovascular risk as determined by NHANES 1 model An abnormal 12-lead electrocardiogram (EKG) suggestive of cardiac disease as determined by a clinician Seropositive for HIV, Hepatitis C virus (antibodies to HCV) and/or HBsAg Hepatomegaly, right upper quadrant abdominal pain or tenderness History of splenectomy Chronic or active neurologic disease including seizure disorder and chronic migraine headaches History of psoriasis and porphyria Acute or chronic, clinically significant pulmonary, cardiovascular, ocular, hematologic, hepatic or renal functional abnormality, as determined by physical examination or abnormal baseline laboratory screening tests and medical history review Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination. For corticosteroids, this is defined as prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed. Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period Current chronic use of medications known to cause drug reactions with chloroquine and/or atovaquone/proguanil such as cimetidine and metoclopramide. Current chronic use or use within one month prior to enrollment of antibiotics with anti-malarial effects such as tetracyclines for acne, sulfa drugs for recurrent urinary tract infections, etc. Pregnant or lactating female Female who is willing or intends to become pregnant during the study and for two (2) months after study completion Any history of allergic reaction or anaphylaxis to previous vaccination History of severe reactions to mosquito bites. Inability to make follow-up visits or complete diary cards Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: p52-p36- GAP Vaccine<br>p52-/p56- GAP Vaccine: Administered by five bites from GAP-infected Anopheles mosquito. p52-/p56- GAP Vaccine: Administered by 200 bites from GAP-infected Anopheles mosquito. Challenge: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum. | Biological: p52-/p36- GAP Vaccine<br>* Administered by five bites from GAP-infected Anopheles mosquito<br>Biological: p52-p36- GAP Vaccine<br>* Administered by 200 bites from GAP-infected Anopeles mosquito<br>|
| No Intervention: Infectivity Control<br>Active Control: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum | |
| Experimental: p52-p36- GAP Vaccine + Infectivity Challenge<br>p52-/p36- GAP Vaccine: Five doses separated by 4-weeks, each administered by 200 bites from GAP-infected Anopheles mosquito. Challenge: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum. | Biological: p52-/p36- GAP Vaccine<br>* Five doses separated by 4-weeks, each administered by 200 bites from GAP-infected Anopheles mosquito<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Solicited Adverse Events (AE) |  | From administration of study vaccine through 7 days (± 1 days) post dosing | 
| Occurrence of Unsolicited AEs |  | From administration of study vaccine through 28 days (± 4 days) post dosing | 
| Occurrence of Laboratory Adverse Events (AE) | Volunteers with any laboratory abnormality. | From administration of study vaccine through 7 days (± 1 days) post dosing | 
| Detection of Breakthrough Peripheral Parasitemia by Thick Blood Film |  | From 7 days after administration of vaccine through 28 days (+ 4 days) post-dosing | 
| Occurrence of Serious Adverse Events (SAE) |  | baseline through 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of Parasitemia and Time to Parasitemia After Primary Malaria Challenge Following Administration of GAP |  | From administration of study vaccine through the duration of the trial | 
| Development of Parasitemia and Time to Parasitemia After Re-challenge Following Administration of GAP |  | From administration of study vaccine through the duration of the trial | 
| P. Falciparum Specific Cell-mediated Immune Responses |  | From administration of study vaccine through the duration of the trial |