Safety of and Immune Response to a Malaria Vaccine (MSP1 42-C1) With or Without CPG 7909 Adjuvant

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of and immune response to a preventive malaria vaccine, MSP1 42-C1/Alhydrogel, in healthy adults. This study will also compare responses to two different doses of the malaria vaccine given with or without the adjuvant CPG 7909.

Detailed Description
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In 2002, the World Health Organization reported a worldwide malaria incidence of approximately 300 million clinical cases annually, with approximately 1 million deaths attributed to malaria alone or in combination with other diseases. The parasite Plasmodium falciparum is responsible for the majority of these infections and deaths. During P. falciparum infection, liver cells are invaded by the parasite and asexual multiplication occurs. The liver cells burst, and tens of thousands of infectious particles called merozoites are released. A multiprotein complex on the surface of a merozoite is necessary for the merozoite to infect a blood cell. MSP1 42-C1 is a malaria vaccine that mimics MSP1 42, a protein in the multiprotein complex. By introducing this decoy form of MSP1 42, infection of additional blood cells may be blocked. The adjuvant CPG 7909 is known to elicit cell-mediated immunity, the arm of the immune system that defends the body against intracellular pathogens such as P. falciparum. This study will evaluate the safety and immunogenicity of MSP1 42-C1/Alhydrogel at two different doses in healthy adults. The vaccine will be given either alone or with CPG 7909. This study will last at least 34 weeks. Participants will be randomly assigned to one of four groups: Group A participants will receive three injections of the lower dose of MSP1 42-C1/Alhydrogel. Group B participants will receive three injections of the lower dose of MSP1 42-C1/Alhydrogel and CPG 7909. Group C participants will receive three injections of the higher dose of MSP1 42-C1/Alhydrogel. Group D participants will receive three injections of the higher dose of MSP1 42-C1/Alhydrogel and CPG 7909. Enrollment into Groups C and D will begin only after safety review of all participants in Groups A and B. All participants will receive their assigned injections at study entry, Week 4, and Week 8, and will be asked to return to the clinic the day after each vaccination for clinical evaluation. Participants will be asked to keep a diary for 6 days after each vaccination, taking note of their body temperatures and any side effects they experience. There will be a total of 18 study visits over 34 weeks. A clinical evaluation will occur at each visit. Blood collection, vital signs measurement, and urine collection will occur at selected visits.

Official Title
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Phase 1 Study of the Safety and Immunogenicity of MSP1 42-C1/Alhydrogel With and Without CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria

Conditions
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Malaria

Intervention / Treatment
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* Biological: MSP1 42-C1/Alhydrogel
* Biological: CPG 7909


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good general health Willing to be followed for the duration of the study Willing to use acceptable methods of contraception Exclusion Criteria: Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may affect the ability of the volunteer to understand and cooperate with the study Liver disease (ALT greater than upper limit of normal [ULN]) Kidney disease (serum creatinine greater than ULN) Hematologic disease (absolute neutrophil count of less than 1,500 cells/mm3; hemoglobin less than lower limit of normal, by sex; OR platelet count less than 140,000 mm3) Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease Participation in another investigational vaccine or drug trial within 30 days of study entry or while this study is ongoing Active drug or alcohol abuse causing medical, occupational, or family problems during the 12 months prior to study entry History of severe allergic reaction or anaphylaxis HIV-1 infected Hepatitis C virus infected Hepatitis B surface antigen positive Known immunodeficiency syndrome Use of corticosteroids or immunosuppressive drugs within 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded. Live vaccine within 4 weeks prior to study entry Killed vaccine within 2 weeks prior to study entry Blood products within 6 months prior to study entry Absence of spleen Previously received an investigational malaria vaccine Received antimalarial prophylaxis during the 12 months prior to study entry Received chloroquine or other aminoquinolines within 12 weeks of study entry Prior malaria infection Known allergy to nickel Pre-existing autoimmune or antibody-mediated disease. More information about this criterion can be found in the protocol. Any medical, psychiatric, social, or occupational condition or other responsibility that, in the opinion of the investigator, would interfere with the study Other condition that, in the opinion of the investigator, would affect the volunteer's participation in the study Pregnancy or breastfeeding

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>3 vaccinations with a dose of 40 mcg MSP1 42-C1/Alhydrogel given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm B. | Biological: MSP1 42-C1/Alhydrogel<br>* Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses)<br>|
| Experimental: B<br>3 vaccinations with a dose of 40 mcg MSP1 42-C1/Alhydrogel and CPG7909 given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm A. | Biological: MSP1 42-C1/Alhydrogel<br>* Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses)<br>Biological: CPG 7909<br>* Adjuvant<br>|
| Experimental: C<br>3 vaccinations with a dose of 160 mcg MSP1 42-C1/Alhydrogel given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm D after review of the results from Arms A and B. | Biological: MSP1 42-C1/Alhydrogel<br>* Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses)<br>|
| Experimental: D<br>3 vaccinations with a dose of 160 mcg MSP1 42-C1/Alhydrogel and CPG7909 given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm C after review of the results from Arms A and B. | Biological: MSP1 42-C1/Alhydrogel<br>* Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses)<br>Biological: CPG 7909<br>* Adjuvant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance |  | Throughout study | 
| Anti-MSP1 42 antibody concentration as measured by ELISA |  | At Day 70 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate that the addition of CPG 7909 improves the specific immune responses to MSP142-FVO and MSP142-3D7, as compared to MSP142-C1/Alhydrogel |  | At Day 70 | 
| To determine the dose of MSP142-C1/Alhydrogel + CPG 7909 that generates the highest serum antibody levels of MSP142-FVO and MSP142-3D7 |  | At Day 70 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmodium falciparum