<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/NCT03821038</url>
  </required_header>
  <id_info>
    <org_study_id>IRIS-7-C&amp;D</org_study_id>
    <nct_id>NCT03821038</nct_id>
  </id_info>
  <brief_title>Recombinant Interleukin-7 (CYT107) to Restore Absolute Lymphocyte Counts in Sepsis Patients</brief_title>
  <acronym>IRIS-7-C&amp;D</acronym>
  <official_title>International, Multicenter, Randomized, Double-blinded, Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) to Restore Absolute Lymphocyte Counts (ALC) in Patients With Sepsis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Revimmune</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Limoges</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>George Clinical Pty Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Revimmune</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II randomized study will assess the effect of receiving IV recombinant human IL-7&#xD;
      (CYT107) versus placebo in lymphopenic sepsis patients&#xD;
&#xD;
      The aim is to confirm the immune cell reconstitution observed in other studies and other&#xD;
      patient populations among which the IRIS-7 A&amp;B study which was conducted in the same patient&#xD;
      population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lymphopenic sepsis Patients will be randomized 3:1 to receive either:&#xD;
&#xD;
      a) Intravenous (IV) administration of CYT107 at 10 μg/kg twice a week for 3 weeks or b) IV&#xD;
      placebo (normal saline).&#xD;
&#xD;
      The effect of CYT107 on Lymphocyte and various T cell populations will be documented with a&#xD;
      focus on the first 29 days.&#xD;
&#xD;
      Stopping rules will apply if ALC increases to &gt;2.5 times the upper limit of normal range.&#xD;
&#xD;
      The IRIS-7C &amp; D studies will be conducted at multiple sites in France and the United States.&#xD;
      All sites will use the same study design and similar study protocol for a common statistical&#xD;
      analysis of 40 evaluable participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    PK issue detected after bolus IV route administration&#xD;
  </why_stopped>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Actual">October 6, 2021</completion_date>
  <primary_completion_date type="Actual">October 6, 2021</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>
    <intervention_model_description>International, multicenter, randomized, double-blinded placebo- controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Open-label pharmacist will prepare masked syringes for the ICU</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Lymphocyte reconstitution</measure>
    <time_frame>day 29 versus baseline</time_frame>
    <description>Change in absolute lymphocyte count (ALC) of ≥ 50%. If this 50% increase over baseline is reached in the placebo group due to natural immune reconstitution, then the day 29 percent increase of ALC over baseline will be compared between the two groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>90 days after study treatment initiation</time_frame>
    <description>Incidence and scoring of all grade 3-4 adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Infections</measure>
    <time_frame>within 90 days after treatment initiation</time_frame>
    <description>Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days in the ICU</measure>
    <time_frame>within 90 days after treatment initiation</time_frame>
    <description>Number of days in ICU following study treatment initiation during the index hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>readmissions to the ICU</measure>
    <time_frame>within 90 days after treatment initiation</time_frame>
    <description>Number of readmissions to ICU following study treatment initiation during index hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>organ support free days</measure>
    <time_frame>within 90 days after treatment initiation</time_frame>
    <description>Number of organ support free days (OSFDs) following study treatment initiation during the index hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>re-hospitalization</measure>
    <time_frame>within 90 days following study treatment initiation</time_frame>
    <description>the incidence of re-hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality rate</measure>
    <time_frame>90 days after study treatment initiation</time_frame>
    <description>All-cause mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T cell reconstitution</measure>
    <time_frame>through day 90</time_frame>
    <description>Absolute numbers of CD4+ and CD8+T-cell counts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients reaching normal ALC</measure>
    <time_frame>through day 90</time_frame>
    <description>Percentage of patients reaching absolute lymphocyte counts (ALC) &gt; 1200</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of IL-7 receptor</measure>
    <time_frame>through day 90</time_frame>
    <description>Effects on soluble and cellular IL-7 receptor (CD127) expression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of HLA-DR on monocytes</measure>
    <time_frame>through day 90</time_frame>
    <description>Effects on circulating monocyte HLA-DR expression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of IL-6 blood levels</measure>
    <time_frame>through day 90</time_frame>
    <description>Effects on whole blood circulating cytokines IL-6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of IL-10 blood levels</measure>
    <time_frame>through day 90</time_frame>
    <description>Effects on whole blood circulating IL-10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of TNF-α blood levels</measure>
    <time_frame>through day 90</time_frame>
    <description>Effects on whole blood circulating TNF-α</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CYT107 Pharmacokinetic Tmax</measure>
    <time_frame>Day 1 and Day 15</time_frame>
    <description>determination of Tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CYT107 Pharmacokinetic Cmax</measure>
    <time_frame>Day 1 and Day 15</time_frame>
    <description>determination of Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CYT107 Pharmacokinetic half life</measure>
    <time_frame>Day 1 and Day 15</time_frame>
    <description>determination of half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CYT107 Pharmacokinetic clearance</measure>
    <time_frame>Day 1 and Day 15</time_frame>
    <description>determination of clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CYT107 Pharmacokinetic area under curve</measure>
    <time_frame>Day 1 and Day 15</time_frame>
    <description>determination of area under curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-CYT107 antibodies</measure>
    <time_frame>day 1, day 29 or hospital discharge, day 90 and day 180 if previous sample positive</time_frame>
    <description>Quantification of circulating anti-CYT107 antibodies</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Sepsis, Severe</condition>
  <arm_group>
    <arm_group_label>CYT107</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous (IV) administration of CYT107 at 10 μg/kg twice a week for 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous (IV) administration of the same volume of NaCl 0.9% twice a week for 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CYT107</intervention_name>
    <description>IV twice a week at 10µg/kg for 3 weeks</description>
    <arm_group_label>CYT107</arm_group_label>
    <other_name>human recombinant glycosylated Interleukin-7</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>IV twice a week at the same volume for 3 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>saline solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. A written, signed informed consent, by the patient or the patient's legally authorized&#xD;
             representative&#xD;
&#xD;
          2. Participants with an absolute lymphocyte count (ALC) ≤ 900 cells/mm3, at two time&#xD;
             points at least twelve hours apart, following diagnosis of vasopressor dependent&#xD;
             sepsis and,&#xD;
&#xD;
               1. the second time point should not be performed earlier than 48 hours after sepsis&#xD;
                  diagnosis,&#xD;
&#xD;
               2. study drug treatment initiation is required no later than 120 hours (up to 5&#xD;
                  days) after the last qualifying ALC ≤ 900 cells/mm3 measure, and&#xD;
&#xD;
               3. the average value of the two qualifying ALC counts will serve as a baseline to&#xD;
                  express the percent increase at day 29, or at hospital discharge.&#xD;
&#xD;
          3. Patients in the ICU with onset of vasopressor dependent sepsis defined as hypotension&#xD;
             requiring treatment with any vasopressor(s) for at least 6 hours to maintain a&#xD;
             systolic pressure ≥ 90 mmHg or a mean arterial pressure ≥65 mmHg AND at least 1 of the&#xD;
             2 organ dysfunction criteria below:&#xD;
&#xD;
               1. Acute respiratory failure defined as the need for invasive mechanical ventilation&#xD;
                  for at least 24 hours to support pulmonary function&#xD;
&#xD;
               2. Acute kidney injury defined as creatinine &gt; 2.0 mg/dL (based on new abnormal&#xD;
                  result following onset of sepsis) OR urine output &lt; 0.5 mL/kg/hr for &gt; 4 hours&#xD;
                  despite adequate fluid resuscitation. In the presence of pre-existing impairment&#xD;
                  of renal function (defined as a serum creatinine concentration &gt;2 times the upper&#xD;
                  limit of the normal reference range prior to the onset of sepsis), the patient&#xD;
                  must meet the other organ dysfunction criteria.&#xD;
&#xD;
          4. Anticipated hospital duration of up to approx. three weeks after initiating study drug&#xD;
             treatment to allow 6 study drug administrations (Days 18 or 19 would be final dose)&#xD;
&#xD;
          5. This study permits the re-enrollment of a participant who may have been discontinued&#xD;
             as a pre-treatment screen failure and/or prior to study drug treatment.&#xD;
&#xD;
          6. Age and reproductive status:&#xD;
&#xD;
               1. Women of childbearing potential (WOCBP) must have a negative serum or urine&#xD;
                  pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24&#xD;
                  hours prior to the start of study treatment&#xD;
&#xD;
               2. Women must not be breastfeeding&#xD;
&#xD;
               3. Women of childbearing potential (WOCBP) must agree to follow instructions for&#xD;
                  method(s) of contraception for the duration of treatment with CYT107 plus 5&#xD;
                  half-lives of CYT107 (the terminal half-life of CYT107 is up to 2 days) plus 30&#xD;
                  days (duration of ovulatory cycle) for a total of 2 months post-treatment&#xD;
                  completion.&#xD;
&#xD;
               4. Males who are sexually active with WOCBP must agree to follow instructions for&#xD;
                  method(s) of contraception for the duration of treatment with CYT107 plus 5&#xD;
                  half-lives of CYT107 plus 90 days (duration of sperm turnover) for a total of 7&#xD;
                  months post-treatment completion. In addition, male participants must be willing&#xD;
                  to refrain from sperm donation during this time.&#xD;
&#xD;
               5. Azoospermic males are exempt from contraceptive requirements.&#xD;
&#xD;
               6. WOCBP who are continuously not heterosexually active are also exempt from&#xD;
                  contraceptive requirements but still must undergo pregnancy testing.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Cancer with current chemotherapy or radiotherapy (receipt of chemotherapy or&#xD;
             radiotherapy for cancer within the last 6 weeks). All patients with current, or&#xD;
             history of, hematologic malignancy (including, but not limited to, ALL, AML, CLL, CML,&#xD;
             etc.) or lymphoma will be excluded, regardless of receipt of recent chemotherapy&#xD;
&#xD;
          2. Patients with minimal chance of survival and life expectancy less than 3-5 days as&#xD;
             defined by an APACHE II score of ≥ 35 at time of consideration for study eligibility&#xD;
&#xD;
          3. Patients with history or current evidence of autoimmune disease including for example:&#xD;
             myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosus, multiple&#xD;
             sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis,&#xD;
             Wegener's etc.&#xD;
&#xD;
          4. Patients who have received a solid organ transplant or bone marrow transplant.&#xD;
&#xD;
          5. Patients with active or a history of acute or chronic lymphocytic leukemia&#xD;
&#xD;
          6. AIDS-defining illness (category C) diagnosed within the last 12 months prior to study&#xD;
             entry&#xD;
&#xD;
          7. Known history of chronic HBV infection and not on treatment with HBV nucleoside&#xD;
             analogues prior to the current hospitalization or HBV DNA &gt; 100 IU/mL&#xD;
&#xD;
          8. Known history of infection with HCV and currently undergoing treatment for HCV&#xD;
             infections or has detectable HCV RNA&#xD;
&#xD;
          9. Known history of tuberculosis and currently undergoing treatment for tuberculosis&#xD;
&#xD;
         10. History of splenectomy&#xD;
&#xD;
         11. Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary&#xD;
             spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia&#xD;
&#xD;
         12. Participation in another investigational interventional study testing a drug or a&#xD;
             medical device within the last 3 months prior to study entry&#xD;
&#xD;
         13. Patients receiving immunosuppressive drugs, e.g., TNF-alpha inhibitors, for any&#xD;
             reason, or systemic corticosteroids other than hydrocortisone at a dose of 300 mg/day&#xD;
&#xD;
         14. Patients receiving concurrent immunotherapy or biologic agents; including growth&#xD;
             factors, cytokines and interleukins other than the study medication : IL-2,&#xD;
             Interferons α, β and γ, GM-CSF, G-CSF, HIV vaccines, immunosuppressive drugs,&#xD;
             hydroxyurea, immunoglobulins, adoptive cell therapy&#xD;
&#xD;
         15. Prior exposure to IL 7 or other drugs specifically targeting T cells&#xD;
&#xD;
         16. Presence of an advanced directive to withhold or withdraw life-sustaining treatment,&#xD;
             DNR order or no CPR order, or comfort measures only order&#xD;
&#xD;
         17. Patients for whom prognosis is poor and source control of septic event is considered&#xD;
             unlikely per the clinical and research teams.&#xD;
&#xD;
         18. Patients under guardianship&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Hotchkiss, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bruno François, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Limoges Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610-0108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital HENRI MONDOR</name>
      <address>
        <city>Créteil</city>
        <zip>94300</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Dijon Bourgogne</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Limoges</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chr Orleans</name>
      <address>
        <city>Orleans</city>
        <zip>45067</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital COCHIN</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chru Bretonneau</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Francois B, Jeannet R, Daix T, Walton AH, Shotwell MS, Unsinger J, Monneret G, Rimmele T, Blood T, Morre M, Gregoire A, Mayo GA, Blood J, Durum SK, Sherwood ER, Hotchkiss RS. Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight. 2018 Mar 8;3(5):e98960. doi: 10.1172/jci.insight.98960.</citation>
    <PMID>29515037</PMID>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>October 19, 2021</last_update_submitted>
  <last_update_submitted_qc>October 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sepsis</keyword>
  <keyword>IL-7</keyword>
  <keyword>lymphocytopenia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Study results will be published Individual data can't be shared and are protected by the new GDPR rule</ipd_description>
  </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/NCT03821038
org study id: IRIS-7-C&D
nct id: NCT03821038
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II randomized study will assess the effect of receiving IV recombinant human IL-7
      (CYT107) versus placebo in lymphopenic sepsis patients

      The aim is to confirm the immune cell reconstitution observed in other studies and other
      patient populations among which the IRIS-7 A&B study which was conducted in the same patient
      population.
Lymphopenic sepsis Patients will be randomized 3:1 to receive either:

      a) Intravenous (IV) administration of CYT107 at 10 μg/kg twice a week for 3 weeks or b) IV
      placebo (normal saline).

      The effect of CYT107 on Lymphocyte and various T cell populations will be documented with a
      focus on the first 29 days.

      Stopping rules will apply if ALC increases to >2.5 times the upper limit of normal range.

      The IRIS-7C & D studies will be conducted at multiple sites in France and the United States.
      All sites will use the same study design and similar study protocol for a common statistical
      analysis of 40 evaluable participants.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: International, multicenter, randomized, double-blinded placebo- controlled
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Open-label pharmacist will prepare masked syringes for the ICU
measure: Lymphocyte reconstitution
time frame: day 29 versus baseline
description: Change in absolute lymphocyte count (ALC) of ≥ 50%. If this 50% increase over baseline is reached in the placebo group due to natural immune reconstitution, then the day 29 percent increase of ALC over baseline will be compared between the two groups.
measure: adverse events
time frame: 90 days after study treatment initiation
description: Incidence and scoring of all grade 3-4 adverse events
measure: Secondary Infections
time frame: within 90 days after treatment initiation
description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC)
measure: Days in the ICU
time frame: within 90 days after treatment initiation
description: Number of days in ICU following study treatment initiation during the index hospitalization
measure: readmissions to the ICU
time frame: within 90 days after treatment initiation
description: Number of readmissions to ICU following study treatment initiation during index hospitalization
measure: organ support free days
time frame: within 90 days after treatment initiation
description: Number of organ support free days (OSFDs) following study treatment initiation during the index hospitalization
measure: re-hospitalization
time frame: within 90 days following study treatment initiation
description: the incidence of re-hospitalization
measure: Mortality rate
time frame: 90 days after study treatment initiation
description: All-cause mortality
measure: T cell reconstitution
time frame: through day 90
description: Absolute numbers of CD4+ and CD8+T-cell counts
measure: Percentage of patients reaching normal ALC
time frame: through day 90
description: Percentage of patients reaching absolute lymphocyte counts (ALC) > 1200
measure: Quantification of IL-7 receptor
time frame: through day 90
description: Effects on soluble and cellular IL-7 receptor (CD127) expression
measure: Quantification of HLA-DR on monocytes
time frame: through day 90
description: Effects on circulating monocyte HLA-DR expression
measure: Change of IL-6 blood levels
time frame: through day 90
description: Effects on whole blood circulating cytokines IL-6
measure: Change of IL-10 blood levels
time frame: through day 90
description: Effects on whole blood circulating IL-10
measure: Change of TNF-α blood levels
time frame: through day 90
description: Effects on whole blood circulating TNF-α
measure: CYT107 Pharmacokinetic Tmax
time frame: Day 1 and Day 15
description: determination of Tmax
measure: CYT107 Pharmacokinetic Cmax
time frame: Day 1 and Day 15
description: determination of Cmax
measure: CYT107 Pharmacokinetic half life
time frame: Day 1 and Day 15
description: determination of half-life
measure: CYT107 Pharmacokinetic clearance
time frame: Day 1 and Day 15
description: determination of clearance
measure: CYT107 Pharmacokinetic area under curve
time frame: Day 1 and Day 15
description: determination of area under curve
measure: anti-CYT107 antibodies
time frame: day 1, day 29 or hospital discharge, day 90 and day 180 if previous sample positive
description: Quantification of circulating anti-CYT107 antibodies
arm group label: CYT107
arm group type: Experimental
description: Intravenous (IV) administration of CYT107 at 10 μg/kg twice a week for 3 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Intravenous (IV) administration of the same volume of NaCl 0.9% twice a week for 3 weeks
intervention type: Biological
intervention name: CYT107
description: IV twice a week at 10µg/kg for 3 weeks
arm group label: CYT107
other name: human recombinant glycosylated Interleukin-7
intervention type: Drug
intervention name: Placebos
description: IV twice a week at the same volume for 3 weeks
arm group label: Placebo
other name: saline solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Richard Hotchkiss, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
last name: Bruno François, MD
role: Principal Investigator
affiliation: Limoges Hospital
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country: France
country: United States
citation: Francois B, Jeannet R, Daix T, Walton AH, Shotwell MS, Unsinger J, Monneret G, Rimmele T, Blood T, Morre M, Gregoire A, Mayo GA, Blood J, Durum SK, Sherwood ER, Hotchkiss RS. Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight. 2018 Mar 8;3(5):e98960. doi: 10.1172/jci.insight.98960.
PMID: 29515037
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
sharing ipd: No
ipd description: Study results will be published Individual data can't be shared and are protected by the new GDPR rule