<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/NCT01660854</url>
  </required_header>
  <id_info>
    <org_study_id>TIP4</org_study_id>
    <nct_id>NCT01660854</nct_id>
  </id_info>
  <brief_title>Re-exposure of Human Volunteers to a Heterologous Strain of P. Falciparum Sporozoites</brief_title>
  <acronym>TIP4</acronym>
  <official_title>Re-exposure of Previously Immunized and Challenged Human Volunteers to a Heterologous Strain of P. Falciparum Sporozoites</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In a previous study (NL33904.091.10) the investigators challenged 24 volunteers after&#xD;
      Chloroquine Prophylaxis Sporozoites (CPS) immunization with 45, 30 or 15 infected&#xD;
      mosquito-bites respectively. The availability of this immunized cohort opens the unique&#xD;
      opportunity to determine protection to a heterologous challenge for both of the protected and&#xD;
      unprotected volunteers as the previous challenge infection might have served as immunological&#xD;
      boost to the unprotected volunteers.&#xD;
&#xD;
      In the current observational, proof of principle study, the investigators aim to investigate&#xD;
      the protection on an individual basis of these previously immunized and challenged volunteers&#xD;
      against a heterologous P. falciparum challenge.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">January 2013</completion_date>
  <primary_completion_date type="Actual">January 2013</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duration of prepatent period after challenge infection as measured by microscopy</measure>
    <time_frame>21 days after challenge</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>• Parasitemia and kinetics of parasitemia as measured by PCR</measure>
    <time_frame>21 days after challenge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of signs or symptoms in study groups</measure>
    <time_frame>21 days after challenge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Immune responses between study groups</measure>
    <time_frame>21 days after challenge</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Malaria, Falciparum</condition>
  <arm_group>
    <arm_group_label>Heterologous challenge</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Biological: Heterologous challenge with 5 infected mosquito bites (NF135) after previous CPS immunization and challenge.&#xD;
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.&#xD;
Other Name: atovaquone/proguanil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Challenge control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Biological: Plasmodium falciparum mosquito challenge by the bites of 5 Plasmodium falciparum infected mosquitoes (NF135).&#xD;
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.&#xD;
Other Name: atovaquone/proguanil</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Heterologous challenge</intervention_name>
    <description>challenge by the bites of 5 Plasmodium falciparum infected mosquitoes.</description>
    <arm_group_label>Challenge control</arm_group_label>
    <arm_group_label>Heterologous challenge</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Malarone treatment</intervention_name>
    <description>Three days: 4 tablets 250/100mg per day</description>
    <arm_group_label>Challenge control</arm_group_label>
    <arm_group_label>Heterologous challenge</arm_group_label>
    <other_name>atovaquon/proguanil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 and ≤ 35 years healthy volunteers (males or females)&#xD;
&#xD;
          2. Good health based on history and clinical examination&#xD;
&#xD;
          3. Negative pregnancy test&#xD;
&#xD;
          4. Use of adequate contraception for females&#xD;
&#xD;
          5. Signing of the informed consent form, thereby demonstrating understanding of the&#xD;
             meaning and procedures of the study&#xD;
&#xD;
          6. Agreement to inform the general practitioner and to sign a request to release medical&#xD;
             information concerning contra-indications for participation in the study&#xD;
&#xD;
          7. Willingness to undergo a Pf controlled challenge through mosquito bites&#xD;
&#xD;
          8. Agreement to stay in a hotel room close to the trial centre during a part of the study&#xD;
             (Day 5 after challenge till treatment is finished)&#xD;
&#xD;
          9. Reachable (24/7) by mobile phone during the whole study period&#xD;
&#xD;
         10. Available to attend all study visit&#xD;
&#xD;
         11. Agreement to refrain from blood donation to Sanquin or for other purposes, during the&#xD;
             whole study period&#xD;
&#xD;
         12. Willingness to undergo HIV, hepatitis B and hepatitis C tests&#xD;
&#xD;
         13. Negative urine toxicology screening test at screening visit and the day before&#xD;
             challenge&#xD;
&#xD;
         14. Willingness to take a curative regimen of Malarone®&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of malaria (other than participation in ZonMw1 study) or residence in malaria&#xD;
             endemic areas within the past six months&#xD;
&#xD;
          2. Plans to travel to malaria endemic areas during the study period&#xD;
&#xD;
          3. Plans to travel outside of the Netherlands during the challenge period&#xD;
&#xD;
          4. Previous participation in any malaria vaccine study and/or positive serology for Pf&#xD;
             (except ZonMw1 volunteers)&#xD;
&#xD;
          5. Symptoms, physical signs and laboratory values suggestive of systemic disorders&#xD;
             including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency,&#xD;
             psychiatric, and other conditions which could interfere with the interpretation of the&#xD;
             study results or compromise the health of the volunteers&#xD;
&#xD;
          6. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)&#xD;
&#xD;
          7. History of arrhythmias or prolonged QT-interval&#xD;
&#xD;
          8. Positive family history in 1st and 2nd degree relatives for cardiac events &lt; 50 years&#xD;
             old&#xD;
&#xD;
          9. An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by&#xD;
             the Systematic Coronary Risk Evaluation (SCORE) system&#xD;
&#xD;
         10. Clinically significant abnormalities in electrocardiogram (ECG) at screening&#xD;
&#xD;
         11. Body Mass Index (BMI) below 18 or above 30 kg/m2&#xD;
&#xD;
         12. Any clinically significant deviation from the normal range in biochemistry or&#xD;
             hematology blood tests or in urine analysis&#xD;
&#xD;
         13. Positive HIV, HBV or HCV tests&#xD;
&#xD;
         14. Participation in any other clinical study within 30 days prior to the onset of the&#xD;
             study&#xD;
&#xD;
         15. Enrollment in any other clinical study during the study period&#xD;
&#xD;
         16. For women: being pregnant or lactating&#xD;
&#xD;
         17. Volunteers unable to give written informed consent&#xD;
&#xD;
         18. Volunteers unable to be closely followed for social, geographic or psychological&#xD;
             reasons&#xD;
&#xD;
         19. History of drug or alcohol abuse interfering with normal social function&#xD;
&#xD;
         20. A history of treatment for psychiatric disease&#xD;
&#xD;
         21. A history of convulsions&#xD;
&#xD;
         22. Contra-indications to Malarone®, including hypersensitivity or treatment taken by the&#xD;
             volunteer that interferes with Malarone®&#xD;
&#xD;
         23. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying&#xD;
             drugs within three months of study onset (inhaled and topical corticosteroids and oral&#xD;
             anti-histaminic are allowed) and during the study period&#xD;
&#xD;
         24. Any confirmed or suspected immunosuppressive or immunodeficient condition, including&#xD;
             (functional) asplenia&#xD;
&#xD;
         25. Co-workers or trainees of the departments Infectious Diseases, Medical Microbiology or&#xD;
             Parasitology of the Leiden University Medical Centre (LUMC) or Medical Microbiology,&#xD;
             Parasitology, Radboud University Nijmegen (RUNMC)&#xD;
&#xD;
         26. A history of sickle cell anaemia, sickle cell trait, thalassaemia (or trait), G6PD&#xD;
             deficiency&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>RW Sauerwein, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Leiden University Medical Centre</name>
      <address>
        <city>Leiden</city>
        <zip>2333ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.</citation>
    <PMID>19641203</PMID>
  </reference>
  <verification_date>July 2012</verification_date>
  <study_first_submitted>July 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>February 12, 2013</last_update_submitted>
  <last_update_submitted_qc>February 12, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 13, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Plasmodium</keyword>
  <keyword>falciparum</keyword>
  <keyword>malaria</keyword>
  <keyword>heterologous</keyword>
  <keyword>immunity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
    <mesh_term>Malaria, Falciparum</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Proguanil</mesh_term>
    <mesh_term>Atovaquone, proguanil drug combination</mesh_term>
  </intervention_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/NCT01660854
org study id: TIP4
nct id: NCT01660854
lead sponsor: 
collaborator: 
has dmc: Yes
In a previous study (NL33904.091.10) the investigators challenged 24 volunteers after
      Chloroquine Prophylaxis Sporozoites (CPS) immunization with 45, 30 or 15 infected
      mosquito-bites respectively. The availability of this immunized cohort opens the unique
      opportunity to determine protection to a heterologous challenge for both of the protected and
      unprotected volunteers as the previous challenge infection might have served as immunological
      boost to the unprotected volunteers.

      In the current observational, proof of principle study, the investigators aim to investigate
      the protection on an individual basis of these previously immunized and challenged volunteers
      against a heterologous P. falciparum challenge.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Duration of prepatent period after challenge infection as measured by microscopy
time frame: 21 days after challenge
measure: • Parasitemia and kinetics of parasitemia as measured by PCR
time frame: 21 days after challenge
measure: Frequency of signs or symptoms in study groups
time frame: 21 days after challenge
measure: • Immune responses between study groups
time frame: 21 days after challenge
arm group label: Heterologous challenge
arm group type: Experimental
description: Biological: Heterologous challenge with 5 infected mosquito bites (NF135) after previous CPS immunization and challenge.
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.
Other Name: atovaquone/proguanil
arm group label: Challenge control
arm group type: Active Comparator
description: Biological: Plasmodium falciparum mosquito challenge by the bites of 5 Plasmodium falciparum infected mosquitoes (NF135).
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.
Other Name: atovaquone/proguanil
intervention type: Biological
intervention name: Heterologous challenge
description: challenge by the bites of 5 Plasmodium falciparum infected mosquitoes.
arm group label: Challenge control
arm group label: Heterologous challenge
intervention type: Drug
intervention name: Malarone treatment
description: Three days: 4 tablets 250/100mg per day
arm group label: Challenge control
arm group label: Heterologous challenge
other name: atovaquon/proguanil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: RW Sauerwein, PhD
role: Study Director
affiliation: Radboud University Medical Center
facility: 
country: Netherlands
citation: Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.
PMID: 19641203
responsible party type: Sponsor
mesh term: Malaria
mesh term: Malaria, Falciparum
mesh term: Proguanil
mesh term: Atovaquone, proguanil drug combination