<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/NCT04447898</url>
  </required_header>
  <id_info>
    <org_study_id>PPV06-01</org_study_id>
    <nct_id>NCT04447898</nct_id>
  </id_info>
  <brief_title>Dose Escalation Study Assessing the Safety and Immune Response of PPV-06 Vaccine</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, Dose Escalation Phase I Study Assessing the Safety and Immune Response of PPV-06 Vaccine in Patient With Inflammatory Knee Osteoarthritis (KOA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peptinov SAS</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peptinov SAS</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>
      PPV-06 immunotherapy targets interleukin-6 (IL-6), a key molecule of the immune system whose&#xD;
      overproduction is implicated in many inflammatory and autoimmune diseases such as rheumatoid&#xD;
      arthritis and osteoarthritis. The benefit of vaccination with PPV-06 is to induce, in&#xD;
      response to immunizations, the production of antibodies directed against IL-6. The antibodies&#xD;
      produced will neutralize the biological activity of IL-6 involved in the body's inflammatory&#xD;
      process.&#xD;
&#xD;
      The primary objective is to evaluate the safety/tolerability of vaccination with PPV-06.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 18, 2021</start_date>
  <completion_date type="Anticipated">February 28, 2023</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of patients with DLT defined as grade 3 or higher treatment-related adverse events (monitored in all patients during the study treatment until the End of Study (Week 42) or early termination).</measure>
    <time_frame>From Baseline to Week 42 (End of Study)</time_frame>
    <description>The primary outcome measure of this study is to evaluate the safety/tolerability of PPV-06 vaccination</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The occurrence of all adverse events (AEs) and serious adverse events (SAEs), including clinically significant abnormal haematological and biochemical values (monitored during the entire study period until End of Study (Week 42) or early termination).</measure>
    <time_frame>From Baseline to Week 42 (End of Study)</time_frame>
    <description>This secondary outcome measure of this study is to evaluate additional indicators of safety / tolerability</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The quantification of inflammatory markers will be assessed at Baseline, W4, W12, W16, W24, W32 and End of Study (Week 42) or early termination by measuring IL-6, hsCRP and CRPM level in blood</measure>
    <time_frame>From Baseline to Week 42 (End of Study)</time_frame>
    <description>This secondary outcome measure of this study is to evaluate additional indicators of safety / tolerability</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The quantification of Anti-IL-6 antibody production, isotypes characterization and anti-CRM197 antibody level in serum at Baseline, W4, W12, W16, W24, W32 and EoS or early termination</measure>
    <time_frame>From Baseline to Week 42 (End of Study)</time_frame>
    <description>This secondary outcome measure of this study is to evaluate the humoral immune response of PPV-06</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The quantification of Anti-IL-6 neutralizing antibody level in vitro at W4, W12, W16, W24, W32 and EoS or early termination</measure>
    <time_frame>From Baseline to Week 42 (End of Study)</time_frame>
    <description>This secondary outcome measure of this study is to evaluate the humoral immune response of PPV-06</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The quantification of specific T cell response and polarization (Th1, Th2 and Th17) assessed by IFNg, IL-5 and IL-17 Elispot assay at Baseline, W24, W32 or early termination.</measure>
    <time_frame>From Baseline to Week 42 (End of Study)</time_frame>
    <description>This secondary outcome measure of this study is to evaluate the cellular immune response of PPV-06</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The quantification of proliferative CD4+T cells assessed by flow cytometry at Baseline, W24, W32 or early termination.</measure>
    <time_frame>From Baseline to Week 42 (End of Study)</time_frame>
    <description>This secondary outcome measure of this study is to evaluate the cellular immune response of PPV-06</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The frequency of hIL-6 epitope-specific memory B cells assessed by ELISPOT assay, at Baseline, W24, W32 or early termination.</measure>
    <time_frame>From Baseline to Week 42 (End of Study)</time_frame>
    <description>This secondary outcome measure of this study is to evaluate the cellular immune response of PPV-06</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Knee Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>Low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 μg + Montanide™ ISA 51 VG</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 μg + Montanide™ ISA 51 VG</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PPV-06 10 μg</intervention_name>
    <description>Low dose + Montanide™ ISA 51 VG in SC administration = 3 injections on Day 0, Day 28, and Day 112</description>
    <arm_group_label>Low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PPV-06 50 μg</intervention_name>
    <description>High dose+ Montanide™ ISA 51 VG in SC administration = 3 injections on Day 0, Day 28, and Day 112</description>
    <arm_group_label>High dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo+ Montanide™ ISA 51 VG in SC administration = 3 injections on Day 0, Day 28, and Day 112</description>
    <arm_group_label>High dose</arm_group_label>
    <arm_group_label>Low dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female aged over 40 years;&#xD;
&#xD;
          2. Diagnosis of primary inflammatory Knee Osteoarthritis (KOA),&#xD;
&#xD;
          3. Body mass index (BMI) of 18-32 kg/m2 at screening;&#xD;
&#xD;
          4. Patients with normal organ function at baseline&#xD;
&#xD;
          5. Contraceptives measures&#xD;
&#xD;
          6. In the investigator's opinion, the patient is capable and willing to comply with the&#xD;
             requirements of the study;&#xD;
&#xD;
          7. Willing and able to sign a written informed consent;&#xD;
&#xD;
          8. Affiliated to social security insurance.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Systemic Autoimmune or immunodeficiency disease;&#xD;
&#xD;
          2. Administration of non-steroidal anti-inflammatory drug (NSAID):&#xD;
&#xD;
          3. Administration of prednisone or having intra-articular corticosteroid injection or&#xD;
             bolus intramuscular or intravenous treatment with corticosteroids;&#xD;
&#xD;
          4. Patients treated with biologics such as anti-TNFAlpha, anti-IL-6 and anti-CD-20&#xD;
&#xD;
          5. Participation in another investigational drug or vaccine trial;&#xD;
&#xD;
          6. Knee surgery planned before screening and throughout the study;&#xD;
&#xD;
          7. Knee surgery within the year of baseline;&#xD;
&#xD;
          8. Knee trauma within 2 months of baseline;&#xD;
&#xD;
          9. Chronic hepatitis B and/or C infection. Patients with previous infection, resolved in&#xD;
             the past, are eligible;&#xD;
&#xD;
         10. HIV-positivity;&#xD;
&#xD;
         11. History of allergic reaction to any constituents of the study drug;&#xD;
&#xD;
         12. Diagnosis or history of any inflammatory arthritis;&#xD;
&#xD;
         13. Neurologic disorders involving the lower limbs;&#xD;
&#xD;
         14. History of malignancy within the last 5 years;&#xD;
&#xD;
         15. Uncontrolled congestive heart failure or hypertension, unstable heart disease&#xD;
&#xD;
         16. Evidence of any clinically significant abnormality on a chest X-ray which, in the&#xD;
             opinion of the investigator, could represent active infection or latent tuberculosis;&#xD;
&#xD;
         17. Moderate or severe acute illness/infection, persistent diarrhea or vomiting on the day&#xD;
             of vaccination;&#xD;
&#xD;
         18. Received any licensed, non-live vaccine within the 14 days before receipt of any dose&#xD;
             of the study vaccine or is scheduled to receive any licensed, non-live vaccine within&#xD;
             30 days following receipt of any dose of the study vaccine;&#xD;
&#xD;
         19. Receipt of immune globulins, blood or blood-derived products;&#xD;
&#xD;
         20. Pregnant or lactating females;&#xD;
&#xD;
         21. The investigator considers the patient unfit for the study as a result of the medical&#xD;
             interview, physical examination, or screening investigations.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cic Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>François Rannou, MD</last_name>
      <phone>0033 1 58 41 25 48</phone>
      <email>francois.rannou@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>May 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>April 25, 2022</last_update_submitted>
  <last_update_submitted_qc>April 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04447898
org study id: PPV06-01
nct id: NCT04447898
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
PPV-06 immunotherapy targets interleukin-6 (IL-6), a key molecule of the immune system whose
      overproduction is implicated in many inflammatory and autoimmune diseases such as rheumatoid
      arthritis and osteoarthritis. The benefit of vaccination with PPV-06 is to induce, in
      response to immunizations, the production of antibodies directed against IL-6. The antibodies
      produced will neutralize the biological activity of IL-6 involved in the body's inflammatory
      process.

      The primary objective is to evaluate the safety/tolerability of vaccination with PPV-06.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: The proportion of patients with DLT defined as grade 3 or higher treatment-related adverse events (monitored in all patients during the study treatment until the End of Study (Week 42) or early termination).
time frame: From Baseline to Week 42 (End of Study)
description: The primary outcome measure of this study is to evaluate the safety/tolerability of PPV-06 vaccination
measure: The occurrence of all adverse events (AEs) and serious adverse events (SAEs), including clinically significant abnormal haematological and biochemical values (monitored during the entire study period until End of Study (Week 42) or early termination).
time frame: From Baseline to Week 42 (End of Study)
description: This secondary outcome measure of this study is to evaluate additional indicators of safety / tolerability
measure: The quantification of inflammatory markers will be assessed at Baseline, W4, W12, W16, W24, W32 and End of Study (Week 42) or early termination by measuring IL-6, hsCRP and CRPM level in blood
time frame: From Baseline to Week 42 (End of Study)
description: This secondary outcome measure of this study is to evaluate additional indicators of safety / tolerability
measure: The quantification of Anti-IL-6 antibody production, isotypes characterization and anti-CRM197 antibody level in serum at Baseline, W4, W12, W16, W24, W32 and EoS or early termination
time frame: From Baseline to Week 42 (End of Study)
description: This secondary outcome measure of this study is to evaluate the humoral immune response of PPV-06
measure: The quantification of Anti-IL-6 neutralizing antibody level in vitro at W4, W12, W16, W24, W32 and EoS or early termination
time frame: From Baseline to Week 42 (End of Study)
description: This secondary outcome measure of this study is to evaluate the humoral immune response of PPV-06
measure: The quantification of specific T cell response and polarization (Th1, Th2 and Th17) assessed by IFNg, IL-5 and IL-17 Elispot assay at Baseline, W24, W32 or early termination.
time frame: From Baseline to Week 42 (End of Study)
description: This secondary outcome measure of this study is to evaluate the cellular immune response of PPV-06
measure: The quantification of proliferative CD4+T cells assessed by flow cytometry at Baseline, W24, W32 or early termination.
time frame: From Baseline to Week 42 (End of Study)
description: This secondary outcome measure of this study is to evaluate the cellular immune response of PPV-06
measure: The frequency of hIL-6 epitope-specific memory B cells assessed by ELISPOT assay, at Baseline, W24, W32 or early termination.
time frame: From Baseline to Week 42 (End of Study)
description: This secondary outcome measure of this study is to evaluate the cellular immune response of PPV-06
arm group label: Low dose
arm group type: Experimental
description: 10 μg + Montanide™ ISA 51 VG
arm group label: High dose
arm group type: Experimental
description: 50 μg + Montanide™ ISA 51 VG
intervention type: Drug
intervention name: PPV-06 10 μg
description: Low dose + Montanide™ ISA 51 VG in SC administration = 3 injections on Day 0, Day 28, and Day 112
arm group label: Low dose
intervention type: Drug
intervention name: PPV-06 50 μg
description: High dose+ Montanide™ ISA 51 VG in SC administration = 3 injections on Day 0, Day 28, and Day 112
arm group label: High dose
intervention type: Drug
intervention name: Placebo
description: Placebo+ Montanide™ ISA 51 VG in SC administration = 3 injections on Day 0, Day 28, and Day 112
arm group label: High dose
arm group label: Low dose
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
sharing ipd: Undecided