xml: <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/NCT05999825</url>
    </required_header>
    <id_info>
      <org_study_id>Sm-p80</org_study_id>
      <nct_id>NCT05999825</nct_id>
    </id_info>
    <brief_title>Sm-p80 Schistosomiasis Challenge Study</brief_title>
    <official_title>Safety and Preliminary Efficacy of Sm-p80 + GLA-SE (SchistoShield®) Vaccine Against Controlled Human Schistosome Infection in Healthy, Schistosoma-naïve Adults</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Leiden University Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Texas Tech University Health Sciences Center</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>MRC/UVRI and LSHTM Uganda Research Unit</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Leiden University Medical Center</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to learn about the Sm-p80 + GLA-SE (Schistoshield®)&#xD;
        vaccine in healthy participants who have not had schistosomiasis before. The main questions&#xD;
        it aims to answer are:&#xD;
  &#xD;
          -  if the vaccine is safe&#xD;
  &#xD;
          -  if after vaccinated people start producing antibodies&#xD;
  &#xD;
          -  if the vaccine works against schistosomiasis.&#xD;
  &#xD;
        Participants will receive three vaccines (or placebo) and are then exposed to 20 male&#xD;
        Schistosoma cercariae. Afterwards they are treated with praziquantel to cure the infection.&#xD;
  &#xD;
        Researchers will compare the group vaccinated with Schistoshield® and placebo (fake&#xD;
        vaccination) to see if the vaccine has worked.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">April 1, 2025</primary_completion_date>
    <phase>Phase 2</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>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Vaccine efficacy</measure>
      <time_frame>week 12-24, i.e. after challenge</time_frame>
      <description>The protective efficacy of Sm-p80 + GLA-SE to male Sm cercariae measured by the difference in frequency of serum CAA positivity (≥1.0 pg/mL) between the vaccine group and placebo</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety of (repeated) immunisation</measure>
      <time_frame>week 0-12</time_frame>
      <description>Frequency and severity of adverse events after (repeated) immunisation with Sm-p80 + GLA-SE</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immunogenicity</measure>
      <time_frame>week 0-24</time_frame>
      <description>Anti-Sm-p80 IgG antibody titres after (repeated) immunisation with Sm-p80 + GLA-SE measured by ELISA</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Time to CAA positivity</measure>
      <time_frame>week 12-24</time_frame>
      <description>Comparison of time to positive serum CAA test between the vaccine and placebo groups after exposure to male Sm cercariae at week 12</description>
    </other_outcome>
    <other_outcome>
      <measure>Peak CAA levels</measure>
      <time_frame>week 12-24</time_frame>
      <description>Comparison of peak serum CAA concentrations between the vaccine and placebo groups after exposure to male Sm cercariae at week 12</description>
    </other_outcome>
    <other_outcome>
      <measure>Eosinophils</measure>
      <time_frame>week 12-24</time_frame>
      <description>Comparison of peak eosinophil counts between the vaccine and placebo groups after exposure to male Sm cercariae at week 12</description>
    </other_outcome>
    <other_outcome>
      <measure>Antibody responses</measure>
      <time_frame>week 0-24</time_frame>
      <description>Comparison of (glycan) antibody responses directed against Sm antigens between the vaccine and placebo participants as well as between protected and non-protected participants after exposure to male Sm cercariae at week 12 using protein and glycan arrays</description>
    </other_outcome>
    <other_outcome>
      <measure>Cellular responses</measure>
      <time_frame>week 0-24</time_frame>
      <description>Comparison of cellular responses directed against Sm antigens between the vaccine and placebo groups after immunisation and after controlled human infection with Sm cercariae, as well as between protected and non-protected participants</description>
    </other_outcome>
    <other_outcome>
      <measure>In vitro killing</measure>
      <time_frame>week 0-24</time_frame>
      <description>Enumeration of the ability of Sm-p80-specific antibodies from human subjects to kill schistosome larvae in vitro from sera collected prior to each vaccination</description>
    </other_outcome>
    <other_outcome>
      <measure>Transcriptomic profile</measure>
      <time_frame>week 0-24</time_frame>
      <description>Identification, characterization and comparison of gene expression changes as measured using RNA-seq analysis from PBMC between placebo and vaccine groups</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">48</enrollment>
    <condition>Schistosoma Mansoni</condition>
    <condition>Schistosomiasis</condition>
    <arm_group>
      <arm_group_label>Vaccine group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The vaccine group will be immunised three times with 30 μg Sm-p80 + 5 μg GLA-SE i.m. at weeks 0,4, and 8. Participants will be exposed to 20 male Schistosoma mansoni cercariae at week 12.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo control group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>The placebo control group will be immunised three times with saline i.m. at weeks 0,4, and 8. Participants will be exposed to 20 male Schistosoma mansoni cercariae at week 12.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Sm-p80 + GLA-SE Vaccine</intervention_name>
      <description>30 μg Sm-p80 + 5 μg GLA-SE</description>
      <arm_group_label>Vaccine group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>0.9% Sterile Normal Saline</description>
      <arm_group_label>Placebo control group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Schistosoma mansoni infection</intervention_name>
      <description>20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain</description>
      <arm_group_label>Placebo control group</arm_group_label>
      <arm_group_label>Vaccine group</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 will not travel to Schistosoma-endemic countries up until treatment at week&#xD;
               24.&#xD;
  &#xD;
            5. Subject agrees to refrain from blood and plasma donation to Sanquin or for other&#xD;
               purposes throughout the study period.&#xD;
  &#xD;
            6. For female subjects: subject agrees to use adequate contraception and not to&#xD;
               breastfeed for the duration of study.&#xD;
  &#xD;
            7. 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, (severe) psychiatric and&#xD;
               other disorders, which could compromise the health of the participant during the study&#xD;
               or interfere with the interpretation of the study results. These include, but are not&#xD;
               limited to, any of the following:&#xD;
  &#xD;
                 -  body weight &lt;50 kg or Body Mass Index (BMI) &lt;18.0 or &gt;35.0 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;
                 -  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. The chronic use of any drug known to interact with praziquantel, artesunate or&#xD;
               lumefantrine metabolism (e.g. phenytoïn, carbamazepine, phenobarbital, primidon,&#xD;
               dexamethason, rifampicine, cimetidine, flecaïnide, metoprolol, imipramine,&#xD;
               amitriptyline, clomipramine, class IA and III anti-arrythmics, antipsychotics,&#xD;
               antidepressants, macrolides, fluorchinolones, imidazole- and triazole antimycotics,&#xD;
               antihistamines). Because lumefantrine may cause extension of QT-time, chronic use of&#xD;
               drugs with effect on QT interval will result in exclusion from study participation.&#xD;
  &#xD;
            3. Any planned vaccination within 28 days before the start of the trial until the end of&#xD;
               the immunisation phase (week 12), with the exception of SARS-CoV-2 vaccines or&#xD;
               influenza vaccines.&#xD;
  &#xD;
            4. For female subjects: positive serum pregnancy test on the day before first&#xD;
               immunisation.&#xD;
  &#xD;
            5. Any history of schistosomiasis or treatment for schistosomiasis.&#xD;
  &#xD;
            6. Positive serology for schistosomiasis or elevated serum CAA at screening.&#xD;
  &#xD;
            7. Known hypersensitivity to or contra-indications (including co-medication) for use of&#xD;
               praziquantel, artesunate or lumefantrine.&#xD;
  &#xD;
            8. Being an employee or student of the department of Parasitology or Infectious diseases&#xD;
               of the LUMC.&#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, Prof</last_name>
      <role>Principal Investigator</role>
      <affiliation>LUMC</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Meta Roestenberg, Prof</last_name>
      <phone>+31715269111</phone>
      <email>M.Roestenberg@lumc.nl</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Leiden University Medical Center</investigator_affiliation>
      <investigator_full_name>Meta Roestenberg</investigator_full_name>
      <investigator_title>Prof.</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Schistosomiasis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05999825
  org study id: Sm-p80
  nct id: NCT05999825
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The goal of this clinical trial is to learn about the Sm-p80 + GLA-SE (Schistoshield®)
        vaccine in healthy participants who have not had schistosomiasis before. The main questions
        it aims to answer are:
  
          -  if the vaccine is safe
  
          -  if after vaccinated people start producing antibodies
  
          -  if the vaccine works against schistosomiasis.
  
        Participants will receive three vaccines (or placebo) and are then exposed to 20 male
        Schistosoma cercariae. Afterwards they are treated with praziquantel to cure the infection.
  
        Researchers will compare the group vaccinated with Schistoshield® and placebo (fake
        vaccination) to see if the vaccine has worked.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Vaccine efficacy
  time frame: week 12-24, i.e. after challenge
  description: The protective efficacy of Sm-p80 + GLA-SE to male Sm cercariae measured by the difference in frequency of serum CAA positivity (≥1.0 pg/mL) between the vaccine group and placebo
  measure: Safety of (repeated) immunisation
  time frame: week 0-12
  description: Frequency and severity of adverse events after (repeated) immunisation with Sm-p80 + GLA-SE
  measure: Immunogenicity
  time frame: week 0-24
  description: Anti-Sm-p80 IgG antibody titres after (repeated) immunisation with Sm-p80 + GLA-SE measured by ELISA
  measure: Time to CAA positivity
  time frame: week 12-24
  description: Comparison of time to positive serum CAA test between the vaccine and placebo groups after exposure to male Sm cercariae at week 12
  measure: Peak CAA levels
  time frame: week 12-24
  description: Comparison of peak serum CAA concentrations between the vaccine and placebo groups after exposure to male Sm cercariae at week 12
  measure: Eosinophils
  time frame: week 12-24
  description: Comparison of peak eosinophil counts between the vaccine and placebo groups after exposure to male Sm cercariae at week 12
  measure: Antibody responses
  time frame: week 0-24
  description: Comparison of (glycan) antibody responses directed against Sm antigens between the vaccine and placebo participants as well as between protected and non-protected participants after exposure to male Sm cercariae at week 12 using protein and glycan arrays
  measure: Cellular responses
  time frame: week 0-24
  description: Comparison of cellular responses directed against Sm antigens between the vaccine and placebo groups after immunisation and after controlled human infection with Sm cercariae, as well as between protected and non-protected participants
  measure: In vitro killing
  time frame: week 0-24
  description: Enumeration of the ability of Sm-p80-specific antibodies from human subjects to kill schistosome larvae in vitro from sera collected prior to each vaccination
  measure: Transcriptomic profile
  time frame: week 0-24
  description: Identification, characterization and comparison of gene expression changes as measured using RNA-seq analysis from PBMC between placebo and vaccine groups
  arm group label: Vaccine group
  arm group type: Experimental
  description: The vaccine group will be immunised three times with 30 μg Sm-p80 + 5 μg GLA-SE i.m. at weeks 0,4, and 8. Participants will be exposed to 20 male Schistosoma mansoni cercariae at week 12.
  arm group label: Placebo control group
  arm group type: Placebo Comparator
  description: The placebo control group will be immunised three times with saline i.m. at weeks 0,4, and 8. Participants will be exposed to 20 male Schistosoma mansoni cercariae at week 12.
  intervention type: Biological
  intervention name: Sm-p80 + GLA-SE Vaccine
  description: 30 μg Sm-p80 + 5 μg GLA-SE
  arm group label: Vaccine group
  intervention type: Other
  intervention name: Placebo
  description: 0.9% Sterile Normal Saline
  arm group label: Placebo control group
  intervention type: Biological
  intervention name: Schistosoma mansoni infection
  description: 20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain
  arm group label: Placebo control group
  arm group label: Vaccine group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Meta Roestenberg, Prof
  role: Principal Investigator
  affiliation: LUMC
  last name: Meta Roestenberg, Prof
  phone: +31715269111
  email: M.Roestenberg@lumc.nl
  responsible party type: Principal Investigator
  investigator affiliation: Leiden University Medical Center
  investigator full name: Meta Roestenberg
  investigator title: Prof.
  mesh term: Schistosomiasis
  sharing ipd: Undecided