<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03014258</url>
  </required_header>
  <id_info>
    <org_study_id>15-0058</org_study_id>
    <nct_id>NCT03014258</nct_id>
  </id_info>
  <brief_title>A Systems Biology Approach to Malaria Immunity</brief_title>
  <official_title>A Systems Biology Approach to Malaria Immunity: Repetitive Controlled Human Malaria Infection (CHMI) Study in Malaria-Naïve Adults Using NF54 Strain Plasmodium Falciparum (Pf)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase I study that will assess the acquisition of immunity to Pf malaria over the&#xD;
      course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10&#xD;
      healthy adult participants. 10 subjects will initially be challenged with 5 uninfected&#xD;
      mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive,&#xD;
      P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the&#xD;
      final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled&#xD;
      and challenged as infectivity controls. If dropouts occur within the original 10 person&#xD;
      cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to&#xD;
      undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and&#xD;
      infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily&#xD;
      follow-up) to diagnose Pf malaria infection and treat with Coartem(R)&#xD;
      (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur&#xD;
      from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection&#xD;
      is complete and two negative smears separated by a time interval &gt;12 hours have been&#xD;
      documented. A third negative smear &gt;12 hours after the previous two daily smears will be&#xD;
      documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be&#xD;
      treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional&#xD;
      outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor&#xD;
      the development of immunity. The study is expected to last for 48 months and will include&#xD;
      approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve&#xD;
      controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years,&#xD;
      inclusive, from the greater Baltimore community. The primary objective of this study is to&#xD;
      determine whether protective immunity against parasite infection develops following repeat&#xD;
      CHMI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase I study that will assess the acquisition of immunity to Pf malaria over the&#xD;
      course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10&#xD;
      healthy adult participants. 10 subjects will initially be challenged with 5 uninfected&#xD;
      mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive,&#xD;
      P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the&#xD;
      final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled&#xD;
      and challenged as infectivity controls. If dropouts occur within the original 10 person&#xD;
      cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to&#xD;
      undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and&#xD;
      infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily&#xD;
      follow-up) to diagnose Pf malaria infection and treat with Coartem(R)&#xD;
      (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur&#xD;
      from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection&#xD;
      is complete and two negative smears separated by a time interval &gt;12 hours have been&#xD;
      documented. A third negative smear &gt;12 hours after the previous two daily smears will be&#xD;
      documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be&#xD;
      treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional&#xD;
      outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor&#xD;
      the development of immunity. The study is expected to last for 48 months and will include&#xD;
      approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve&#xD;
      controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years,&#xD;
      inclusive, from the greater Baltimore community. The primary objective of this study is to&#xD;
      determine whether protective immunity against parasite infection develops following repeat&#xD;
      CHMI. The secondary objectives are to: 1) determine whether clinical signs and symptoms of&#xD;
      malaria decrease in intensity and duration following repeat CHMI, 2) track the production of&#xD;
      antibodies that react with P. falciparum sporozoites and blood stage parasites.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 7, 2017</start_date>
  <completion_date type="Actual">July 19, 2019</completion_date>
  <primary_completion_date type="Actual">July 19, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of subjects testing positive for parasites</measure>
    <time_frame>Study Day 6 through Study Day 29</time_frame>
    <description>As measured using real-time quantitative polymerase chain reaction (PCR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive malaria smear</measure>
    <time_frame>Study Day 9 through Study Day 29</time_frame>
    <description>For infectivity controls enrolled into infective CHMI #5, malaria detection will rely upon ultra-sensitive quantitative polymerase chain reaction (us-qPCR) to ensure safety while conducting this portion of the study as an outpatient</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantification of parasite infection</measure>
    <time_frame>Study Day 6 through Study Day 29</time_frame>
    <description>As measured using real-time quantitative polymerase chain reaction (PCR) during the surveillance period after infected CHMI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Antibody reactivity against Circumsporozoite protein (CSP)</measure>
    <time_frame>Up to Study Day 21</time_frame>
    <description>Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody reactivity against Glutamate-rich protein (GLURP)</measure>
    <time_frame>Up to Study Day 21</time_frame>
    <description>Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody reactivity against Plasmodium Falciparum liver- and erythrocytic-stage antigen</measure>
    <time_frame>Up to Study Day 21</time_frame>
    <description>Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody reactivity against Plasmodium Falciparum pre-erythrocytic antigen</measure>
    <time_frame>Up to Study Day 21</time_frame>
    <description>Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects displaying signs and symptoms attributable to malaria</measure>
    <time_frame>Study Day 6 through Study Day 29</time_frame>
    <description>Such as malaise, chills/rigors, nausea, vomiting, dizziness, arthralgia, abdominal pain, myalgia, and headache</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects with fever attributable to malaria</measure>
    <time_frame>Study Day 6 through Study Day 29</time_frame>
    <description>Fever as defined as &gt;38 degrees Celsius</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Plasmodium Falciparum Infection</condition>
  <arm_group>
    <arm_group_label>Control Cohort 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Immunologic malaria-naïve subjects will undergo CHMI #2 with 5 NF54 P. falciparum-infected mosquitoes at months 8-9. n=6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Cohort 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Immunologic malaria-naïve subjects will undergo a CHMI #3 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #2. n=6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Cohort 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Immunologic malaria-naïve subjects will undergo a CHMI #4 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #3. n=6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Cohort 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Immunologic malaria-naïve subjects will undergo a CHMI #5 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #4. n=6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Repeat CHMI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will initially be challenged with 5 uninfected mosquitoes (mock), followed by 5 challenges (CHMI # 1-5) with 5 NF54 P. falciparum-infected mosquitoes 2, 8, 14-20, and 20-32, and 32-36 months later. n=10.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>NF54 P. falciparum malaria challenge</intervention_name>
    <description>Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.</description>
    <arm_group_label>Control Cohort 1</arm_group_label>
    <arm_group_label>Control Cohort 2</arm_group_label>
    <arm_group_label>Control Cohort 3</arm_group_label>
    <arm_group_label>Control Cohort 4</arm_group_label>
    <arm_group_label>Repeat CHMI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or non-pregnant/non-lactating female between the ages of 18 and 50 years,&#xD;
             inclusive.&#xD;
&#xD;
          2. Able and willing to participate for the duration of the study.&#xD;
&#xD;
          3. Able to provide proof of identity to the satisfaction of the study clinician&#xD;
             completing the enrollment process.&#xD;
&#xD;
          4. Able and willing to complete the informed consent process.&#xD;
&#xD;
          5. Willing to donate blood for sample storage to be used for future research (Note:&#xD;
             refusal to allow future use is exclusionary).&#xD;
&#xD;
          6. Willing to refrain from blood donation to blood banks for 3 years following P.&#xD;
             falciparum CHMI.&#xD;
&#xD;
          7. Agrees not to travel to a malaria endemic region during the entire course of study&#xD;
             participation.&#xD;
&#xD;
          8. Physical examination and laboratory results without clinically significant findings&#xD;
             and a body mass index (BMI) = / &lt; 35.&#xD;
&#xD;
             Laboratory Criteria within 56 days prior to enrollment:&#xD;
&#xD;
          9. Hemoglobin = / &gt;11.2 g/dL for women; = / &gt; 12.6 g/dL for men.&#xD;
&#xD;
         10. Platelet count within institutional normal range.&#xD;
&#xD;
         11. Alanine aminotransferase (ALT) = / &lt; upper limit of normal.&#xD;
&#xD;
         12. Serum creatinine = / &lt; upper limit of normal.&#xD;
&#xD;
         13. Negative for HIV and Hepatitis B/C infection.&#xD;
&#xD;
             Laboratory Criterion documented any time prior to enrollment:&#xD;
&#xD;
         14. Negative sickle cell screening test.&#xD;
&#xD;
             Female-Specific Criteria:&#xD;
&#xD;
         15. Negative beta-HCG pregnancy test (serum) on day of screening or urine pregnancy test&#xD;
             at subsequent time points for women of childbearing potential.&#xD;
&#xD;
         16. Women of childbearing potential (exclusive of women in a same sex relationship) must&#xD;
             agree to use effective means of birth control.* *(e.g. oral or implanted&#xD;
             contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap,&#xD;
             abstinence, use of a condom by the sexual partner or sterile sexual partner). Women&#xD;
             with a history of amenorrhea (&gt; 1 year duration) or surgical or chemical sterilization&#xD;
             (e.g. tubal ligation, hysterectomy, other) must provide written documentation of&#xD;
             infertility from a health care provider.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who are breast-feeding or planning to become pregnant during the time interval&#xD;
             needed to complete the study.&#xD;
&#xD;
          2. Receipt of a malaria vaccine in a prior clinical trial.&#xD;
&#xD;
          3. Any history of malaria infection.&#xD;
&#xD;
          4. Evidence of increased cardiovascular disease risk; defined as &gt; 10% five year risk by&#xD;
             the non-laboratory method.&#xD;
&#xD;
          5. Current use of systemic immunosuppressant pharmacotherapy.&#xD;
&#xD;
          6. History of a splenectomy, sickle cell disease or sickle cell trait.&#xD;
&#xD;
          7. Known history of anaphylactic response to mosquito-bites; or known allergy to&#xD;
             artemether lumefantrine or atovaquone or proguanil or other component of the product.&#xD;
&#xD;
          8. Participation in any study involving investigational vaccine or drug within 4 weeks&#xD;
             prior to enrollment, or expects to receive vaccine or drug during the 2-month&#xD;
             post-challenge period.&#xD;
&#xD;
          9. Use or planned use of any drug with anti-malarial activity that would coincide with&#xD;
             challenge.&#xD;
&#xD;
         10. Anticipated use of medications known to cause drug reactions with atovaquone-proguanil&#xD;
             (Malarone(R)) such as cimetidine, metoclopramide, antacids, and kaolin.&#xD;
&#xD;
         11. Plans to undergo surgery (elective or otherwise) between enrollment and 4 weeks (28&#xD;
             days) after any of the challenges.&#xD;
&#xD;
         12. Received a licensed vaccine within 1 month prior to enrollment in this study or&#xD;
             expects to receive one during the 28 day post challenge period.&#xD;
&#xD;
         13. History of psychiatric disorders or behavioral tendencies (including active alcohol or&#xD;
             drug abuse) that in the opinion of the investigator would make compliance with the&#xD;
             protocol difficult.* *Medical and psychiatric illness defined as personality&#xD;
             disorders, anxiety disorders, or schizophrenia or social condition, occupational&#xD;
             reason or other responsibility that, in the judgment of the investigator, is a&#xD;
             contraindication to protocol participation or impairs a volunteer's ability to give&#xD;
             informed consent or to comply with the protocol schedule.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Maryland School of Medicine - Center for Vaccine Development - Baltimore</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201-1509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 27, 2021</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>June 3, 2021</last_update_submitted>
  <last_update_submitted_qc>June 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Biology</keyword>
  <keyword>falciparum</keyword>
  <keyword>Immunity</keyword>
  <keyword>Infections</keyword>
  <keyword>Malaria</keyword>
  <keyword>Pf</keyword>
  <keyword>Plasmodium</keyword>
  <keyword>Systems</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03014258
org study id: 15-0058
nct id: NCT03014258
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a phase I study that will assess the acquisition of immunity to Pf malaria over the
      course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10
      healthy adult participants. 10 subjects will initially be challenged with 5 uninfected
      mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive,
      P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the
      final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled
      and challenged as infectivity controls. If dropouts occur within the original 10 person
      cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to
      undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and
      infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily
      follow-up) to diagnose Pf malaria infection and treat with Coartem(R)
      (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur
      from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection
      is complete and two negative smears separated by a time interval >12 hours have been
      documented. A third negative smear >12 hours after the previous two daily smears will be
      documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be
      treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional
      outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor
      the development of immunity. The study is expected to last for 48 months and will include
      approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve
      controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years,
      inclusive, from the greater Baltimore community. The primary objective of this study is to
      determine whether protective immunity against parasite infection develops following repeat
      CHMI.
This is a phase I study that will assess the acquisition of immunity to Pf malaria over the
      course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10
      healthy adult participants. 10 subjects will initially be challenged with 5 uninfected
      mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive,
      P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the
      final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled
      and challenged as infectivity controls. If dropouts occur within the original 10 person
      cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to
      undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and
      infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily
      follow-up) to diagnose Pf malaria infection and treat with Coartem(R)
      (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur
      from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection
      is complete and two negative smears separated by a time interval >12 hours have been
      documented. A third negative smear >12 hours after the previous two daily smears will be
      documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be
      treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional
      outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor
      the development of immunity. The study is expected to last for 48 months and will include
      approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve
      controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years,
      inclusive, from the greater Baltimore community. The primary objective of this study is to
      determine whether protective immunity against parasite infection develops following repeat
      CHMI. The secondary objectives are to: 1) determine whether clinical signs and symptoms of
      malaria decrease in intensity and duration following repeat CHMI, 2) track the production of
      antibodies that react with P. falciparum sporozoites and blood stage parasites.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Percentage of subjects testing positive for parasites
time frame: Study Day 6 through Study Day 29
description: As measured using real-time quantitative polymerase chain reaction (PCR)
measure: Percentage of subjects with positive malaria smear
time frame: Study Day 9 through Study Day 29
description: For infectivity controls enrolled into infective CHMI #5, malaria detection will rely upon ultra-sensitive quantitative polymerase chain reaction (us-qPCR) to ensure safety while conducting this portion of the study as an outpatient
measure: Quantification of parasite infection
time frame: Study Day 6 through Study Day 29
description: As measured using real-time quantitative polymerase chain reaction (PCR) during the surveillance period after infected CHMI.
measure: Antibody reactivity against Circumsporozoite protein (CSP)
time frame: Up to Study Day 21
description: Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.
measure: Antibody reactivity against Glutamate-rich protein (GLURP)
time frame: Up to Study Day 21
description: Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.
measure: Antibody reactivity against Plasmodium Falciparum liver- and erythrocytic-stage antigen
time frame: Up to Study Day 21
description: Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.
measure: Antibody reactivity against Plasmodium Falciparum pre-erythrocytic antigen
time frame: Up to Study Day 21
description: Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.
measure: Percentage of subjects displaying signs and symptoms attributable to malaria
time frame: Study Day 6 through Study Day 29
description: Such as malaise, chills/rigors, nausea, vomiting, dizziness, arthralgia, abdominal pain, myalgia, and headache
measure: Percentage of subjects with fever attributable to malaria
time frame: Study Day 6 through Study Day 29
description: Fever as defined as >38 degrees Celsius
arm group label: Control Cohort 1
arm group type: Active Comparator
description: Immunologic malaria-naïve subjects will undergo CHMI #2 with 5 NF54 P. falciparum-infected mosquitoes at months 8-9. n=6.
arm group label: Control Cohort 2
arm group type: Active Comparator
description: Immunologic malaria-naïve subjects will undergo a CHMI #3 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #2. n=6.
arm group label: Control Cohort 3
arm group type: Active Comparator
description: Immunologic malaria-naïve subjects will undergo a CHMI #4 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #3. n=6.
arm group label: Control Cohort 4
arm group type: Active Comparator
description: Immunologic malaria-naïve subjects will undergo a CHMI #5 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #4. n=6.
arm group label: Repeat CHMI
arm group type: Experimental
description: Subjects will initially be challenged with 5 uninfected mosquitoes (mock), followed by 5 challenges (CHMI # 1-5) with 5 NF54 P. falciparum-infected mosquitoes 2, 8, 14-20, and 20-32, and 32-36 months later. n=10.
intervention type: Biological
intervention name: NF54 P. falciparum malaria challenge
description: Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.
arm group label: Control Cohort 1
arm group label: Control Cohort 2
arm group label: Control Cohort 3
arm group label: Control Cohort 4
arm group label: Repeat CHMI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Malaria