<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/NCT03257072</url>
  </required_header>
  <id_info>
    <org_study_id>ReCHHI1</org_study_id>
    <nct_id>NCT03257072</nct_id>
  </id_info>
  <brief_title>Repeated Controlled Human Hookworm Infection</brief_title>
  <acronym>ReCHHI1</acronym>
  <official_title>Repeated Controlled Human Hookworm Infection in Healthy Dutch Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meta Roestenberg</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Leiden University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Twenty-four healthy hookworm-naive volunteers will be exposed to 50 L3 Necator americanus&#xD;
      larvae for a maximum of three times.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Twenty-four volunteers will be allocated equally into three groups (i.e. group A, B, C).&#xD;
      Group A, B, and C will have one, two, and three infections respectively. Every infection will&#xD;
      be performed with 50 L3 Necator americanus larvae. Group A will receive infection at week 4&#xD;
      only. Group B will be infected at week 2 and week 4. Group C will be infected at week 0, 2&#xD;
      and 4. To maintain blinding, group A and B will receive mock infections with water at week 0&#xD;
      and week 0 and 2 respectively. The interval between each CHHI is 2 weeks. Before every&#xD;
      infection, the safety will be assessed by a review of adverse events data with a local safety&#xD;
      monitor.&#xD;
&#xD;
      Sixteen weeks after the last infection (week 20), all volunteers will be offered treatment&#xD;
      with a 3-day regimen of albendazole to abrogate infection. Volunteers with average egg counts&#xD;
      &gt;250 eggs per gram will be asked if they would be willing to keep their infection for a&#xD;
      maximum of two years (chronic donors). No more than four volunteers will be selected to be&#xD;
      chronic donors. Six months after the last infection (or after the last donation for the&#xD;
      chronic donors) volunteers will undergo their last visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2018</start_date>
  <completion_date type="Actual">August 30, 2018</completion_date>
  <primary_completion_date type="Actual">August 30, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>double-blind, placebo-controlled, dose-escalation trial</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of adverse events</measure>
    <time_frame>28 weeks</time_frame>
    <description>Frequency of adverse events as compared between study groups A, B and C.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Magnitude of adverse events</measure>
    <time_frame>28 weeks</time_frame>
    <description>Magnitude of adverse events as compared between study groups A, B and C.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Variability in egg secretion</measure>
    <time_frame>20 weeks</time_frame>
    <description>Variability in egg secretion by Kato-Katz from week 16 to 20</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lowest dose at which there is 100% patent hookworm infection</measure>
    <time_frame>20 weeks</time_frame>
    <description>The lowest dose at which there is 100% patent hookworm infection, as defined by a positive Kato-Katz at any time between week 16 to 20</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the average number of eggs secreted</measure>
    <time_frame>20 weeks</time_frame>
    <description>Comparison of the average number of eggs secreted by Kato-Katz and qPCR between different groups in weeks 16-20 after the infection</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Necator Americanus Infection</condition>
  <arm_group>
    <arm_group_label>A: 50 Necator americanus L3 larvae</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mock infections with water at week 0 and 2, infection with 50 Necator americanus L3 larvae at week 4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B: 100 Necator americanus L3 larvae</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mock infections with water at week 0, infection with 50 Necator americanus L3 larvae at week 2 and 4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C: 150 Necator americanus L3 larvae</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infection with 50 Necator americanus L3 larvae at week 0, 2 and 4</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>50 Necator americanus L3 larvae</intervention_name>
    <description>1x50 Necator americanus L3 larvae</description>
    <arm_group_label>A: 50 Necator americanus L3 larvae</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>100 Necator americanus L3 larvae</intervention_name>
    <description>2x50 Necator americanus L3 larvae</description>
    <arm_group_label>B: 100 Necator americanus L3 larvae</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>150 Necator americanus L3 larvae</intervention_name>
    <description>3x50 Necator americanus L3 larvae</description>
    <arm_group_label>C: 150 Necator americanus L3 larvae</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is aged ≥ 18 and ≤ 45 years and in good health.&#xD;
&#xD;
          2. Subject has adequate understanding of the procedures of the study and agrees to abide&#xD;
             strictly thereby.&#xD;
&#xD;
          3. Subject is able to communicate well with the investigator, is available to attend all&#xD;
             study visits.&#xD;
&#xD;
          4. Subject agrees to refrain from blood donation to Sanquin or for other purposes&#xD;
             throughout the study period.&#xD;
&#xD;
          5. For female subjects: subject agrees to use adequate contraception and not to&#xD;
             breastfeed for the duration of study.&#xD;
&#xD;
          6. Subject has signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any history, or evidence at screening, of clinically significant symptoms, physical&#xD;
             signs or abnormal laboratory values suggestive of systemic conditions, such as&#xD;
             cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine,&#xD;
             malignant, haematological, infectious, immune-deficient, psychiatric and other&#xD;
             disorders, which could compromise the health of the volunteer during the study or&#xD;
             interfere with the interpretation of the study results. These include, but are not&#xD;
             limited to, any of the following:&#xD;
&#xD;
               -  Body Mass Index (BMI) &lt;18.0 or &gt;30.0 kg/m2 at screening;&#xD;
&#xD;
               -  positive HIV, HBV or HCV screening tests;&#xD;
&#xD;
               -  the use of immune modifying drugs within three months prior to study onset&#xD;
                  (inhaled and topical corticosteroids and oral anti-histamines exempted) or&#xD;
                  expected use of such during the study period;&#xD;
&#xD;
               -  having one of the following laboratory abnormalities: ferritine &lt;10 ug/L,&#xD;
                  transferrine &lt;2.04 g/L or Hb &lt;7.0 mmol/L for females or &lt;8.0 mmol/L for males;&#xD;
&#xD;
               -  history of malignancy of any organ system (other than localized basal cell&#xD;
                  carcinoma of the skin), treated or untreated, within the past 5 years;&#xD;
&#xD;
               -  any history of treatment for severe psychiatric disease by a psychiatrist in the&#xD;
                  past year;&#xD;
&#xD;
               -  history of drug or alcohol abuse interfering with normal social function in the&#xD;
                  period of one year prior to study onset.&#xD;
&#xD;
          2. Known hypersensitivity to or contra-indications for use of albendazole, including&#xD;
             co-medication known to interact with albendazole metabolism (e.g. carbamazepine,&#xD;
             phenobarbital, phenytoin, cimetidine, theophylline, dexamethasone)&#xD;
&#xD;
          3. Known allergy to amphotericin B or gentamicin&#xD;
&#xD;
          4. For female subjects: positive urine pregnancy test at screening&#xD;
&#xD;
          5. Positive faecal qPCR or Kato-Katz for hookworm at screening, any known history of&#xD;
             hookworm infection or treatment for hookworm infection or possible exposure to&#xD;
             hookworm in the past&#xD;
&#xD;
          6. Being an employee or student of the department of parasitology of the LUMC&#xD;
&#xD;
          7. Current or past scars, tattoos, or other disruptions of skin integrity at the intended&#xD;
             site of larval application&#xD;
&#xD;
          8. Subjects with planned travel to hookworm endemic areas during this trial&#xD;
&#xD;
          9. Receipt of a vaccine within 4 weeks prior to the study initiation&#xD;
&#xD;
         10. Known food allergy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Meta Roestenberg, MD. PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>LUMC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Leiden University Medical Center</name>
      <address>
        <city>Leiden</city>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <results_reference>
    <citation>Hoogerwerf MA, Koopman JPR, Janse JJ, Langenberg MCC, van Schuijlenburg R, Kruize YCM, Brienen EAT, Manurung MD, Verbeek-Menken P, van der Beek MT, Westra IM, Meij P, Visser LG, van Lieshout L, de Vlas SJ, Yazdanbakhsh M, Coffeng LE, Roestenberg M. A Randomized Controlled Trial to Investigate Safety and Variability of Egg Excretion After Repeated Controlled Human Hookworm Infection. J Infect Dis. 2021 Mar 3;223(5):905-913. doi: 10.1093/infdis/jiaa414.</citation>
    <PMID>32645714</PMID>
  </results_reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>November 16, 2020</last_update_submitted>
  <last_update_submitted_qc>November 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Leiden University Medical Center</investigator_affiliation>
    <investigator_full_name>Meta Roestenberg</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>hookworm</keyword>
  <keyword>controlled human infection model</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Hookworm Infections</mesh_term>
    <mesh_term>Ancylostomiasis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03257072
org study id: ReCHHI1
nct id: NCT03257072
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Twenty-four healthy hookworm-naive volunteers will be exposed to 50 L3 Necator americanus
      larvae for a maximum of three times.
Twenty-four volunteers will be allocated equally into three groups (i.e. group A, B, C).
      Group A, B, and C will have one, two, and three infections respectively. Every infection will
      be performed with 50 L3 Necator americanus larvae. Group A will receive infection at week 4
      only. Group B will be infected at week 2 and week 4. Group C will be infected at week 0, 2
      and 4. To maintain blinding, group A and B will receive mock infections with water at week 0
      and week 0 and 2 respectively. The interval between each CHHI is 2 weeks. Before every
      infection, the safety will be assessed by a review of adverse events data with a local safety
      monitor.

      Sixteen weeks after the last infection (week 20), all volunteers will be offered treatment
      with a 3-day regimen of albendazole to abrogate infection. Volunteers with average egg counts
      >250 eggs per gram will be asked if they would be willing to keep their infection for a
      maximum of two years (chronic donors). No more than four volunteers will be selected to be
      chronic donors. Six months after the last infection (or after the last donation for the
      chronic donors) volunteers will undergo their last visit.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: double-blind, placebo-controlled, dose-escalation trial
primary purpose: Diagnostic
masking: Triple (Participant, Care Provider, Investigator)
masking description: double-blind
measure: Frequency of adverse events
time frame: 28 weeks
description: Frequency of adverse events as compared between study groups A, B and C.
measure: Magnitude of adverse events
time frame: 28 weeks
description: Magnitude of adverse events as compared between study groups A, B and C.
measure: Variability in egg secretion
time frame: 20 weeks
description: Variability in egg secretion by Kato-Katz from week 16 to 20
measure: Lowest dose at which there is 100% patent hookworm infection
time frame: 20 weeks
description: The lowest dose at which there is 100% patent hookworm infection, as defined by a positive Kato-Katz at any time between week 16 to 20
measure: Comparison of the average number of eggs secreted
time frame: 20 weeks
description: Comparison of the average number of eggs secreted by Kato-Katz and qPCR between different groups in weeks 16-20 after the infection
arm group label: A: 50 Necator americanus L3 larvae
arm group type: Experimental
description: Mock infections with water at week 0 and 2, infection with 50 Necator americanus L3 larvae at week 4
arm group label: B: 100 Necator americanus L3 larvae
arm group type: Experimental
description: Mock infections with water at week 0, infection with 50 Necator americanus L3 larvae at week 2 and 4
arm group label: C: 150 Necator americanus L3 larvae
arm group type: Experimental
description: Infection with 50 Necator americanus L3 larvae at week 0, 2 and 4
intervention type: Biological
intervention name: 50 Necator americanus L3 larvae
description: 1x50 Necator americanus L3 larvae
arm group label: A: 50 Necator americanus L3 larvae
intervention type: Biological
intervention name: 100 Necator americanus L3 larvae
description: 2x50 Necator americanus L3 larvae
arm group label: B: 100 Necator americanus L3 larvae
intervention type: Biological
intervention name: 150 Necator americanus L3 larvae
description: 3x50 Necator americanus L3 larvae
arm group label: C: 150 Necator americanus L3 larvae
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Meta Roestenberg, MD. PhD.
role: Principal Investigator
affiliation: LUMC
facility: 
country: Netherlands
citation: Hoogerwerf MA, Koopman JPR, Janse JJ, Langenberg MCC, van Schuijlenburg R, Kruize YCM, Brienen EAT, Manurung MD, Verbeek-Menken P, van der Beek MT, Westra IM, Meij P, Visser LG, van Lieshout L, de Vlas SJ, Yazdanbakhsh M, Coffeng LE, Roestenberg M. A Randomized Controlled Trial to Investigate Safety and Variability of Egg Excretion After Repeated Controlled Human Hookworm Infection. J Infect Dis. 2021 Mar 3;223(5):905-913. doi: 10.1093/infdis/jiaa414.
PMID: 32645714
responsible party type: Sponsor-Investigator
investigator affiliation: Leiden University Medical Center
investigator full name: Meta Roestenberg
investigator title: Principal Investigator
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Hookworm Infections
mesh term: Ancylostomiasis
sharing ipd: No