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Recombinant Interleukin-7 (CYT107) to Restore Absolute Lymphocyte Counts in Sepsis Patients (IRIS-7-C&D)

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ClinicalTrials.gov Identifier: NCT03821038
Recruitment Status : Recruiting
First Posted : January 29, 2019
Last Update Posted : November 7, 2019
Sponsor:
Collaborators:
Washington University School of Medicine
University Hospital, Limoges
George Clinical Pty Ltd
Information provided by (Responsible Party):
Revimmune

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Sepsis, Severe Biological: CYT107 Drug: Placebos Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: International, multicenter, randomized, double-blinded placebo- controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Open-label pharmacist will prepare masked syringes for the ICU
Primary Purpose: Treatment
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
Actual Study Start Date : June 1, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: CYT107
Intravenous (IV) administration of CYT107 at 10 μg/kg twice a week for 3 weeks
Biological: CYT107
IV twice a week at 10µg/kg for 3 weeks
Other Name: human recombinant glycosylated Interleukin-7

Placebo Comparator: Placebo
Intravenous (IV) administration of the same volume of NaCl 0.9% twice a week for 3 weeks
Drug: Placebos
IV twice a week at the same volume for 3 weeks
Other Name: saline solution




Primary Outcome Measures :
  1. Lymphocyte reconstitution [ Time Frame: day 29 versus baseline ]
    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.


Secondary Outcome Measures :
  1. adverse events [ Time Frame: 90 days after study treatment initiation ]
    Incidence and scoring of all grade 3-4 adverse events

  2. Secondary Infections [ Time Frame: within 90 days after treatment initiation ]
    Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC)

  3. Days in the ICU [ Time Frame: within 90 days after treatment initiation ]
    Number of days in ICU following study treatment initiation during the index hospitalization

  4. readmissions to the ICU [ Time Frame: within 90 days after treatment initiation ]
    Number of readmissions to ICU following study treatment initiation during index hospitalization

  5. organ support free days [ Time Frame: within 90 days after treatment initiation ]
    Number of organ support free days (OSFDs) following study treatment initiation during the index hospitalization

  6. re-hospitalization [ Time Frame: within 90 days following study treatment initiation ]
    the incidence of re-hospitalization

  7. Mortality rate [ Time Frame: 90 days after study treatment initiation ]
    All-cause mortality

  8. T cell reconstitution [ Time Frame: through day 90 ]
    Absolute numbers of CD4+ and CD8+T-cell counts

  9. Percentage of patients reaching normal ALC [ Time Frame: through day 90 ]
    Percentage of patients reaching absolute lymphocyte counts (ALC) > 1200

  10. Quantification of IL-7 receptor [ Time Frame: through day 90 ]
    Effects on soluble and cellular IL-7 receptor (CD127) expression

  11. Quantification of HLA-DR on monocytes [ Time Frame: through day 90 ]
    Effects on circulating monocyte HLA-DR expression

  12. Change of IL-6 blood levels [ Time Frame: through day 90 ]
    Effects on whole blood circulating cytokines IL-6

  13. Change of IL-10 blood levels [ Time Frame: through day 90 ]
    Effects on whole blood circulating IL-10

  14. Change of TNF-α blood levels [ Time Frame: through day 90 ]
    Effects on whole blood circulating TNF-α

  15. CYT107 Pharmacokinetic Tmax [ Time Frame: Day 1 and Day 15 ]
    determination of Tmax

  16. CYT107 Pharmacokinetic Cmax [ Time Frame: Day 1 and Day 15 ]
    determination of Cmax

  17. CYT107 Pharmacokinetic half life [ Time Frame: Day 1 and Day 15 ]
    determination of half-life

  18. CYT107 Pharmacokinetic clearance [ Time Frame: Day 1 and Day 15 ]
    determination of clearance

  19. CYT107 Pharmacokinetic area under curve [ Time Frame: Day 1 and Day 15 ]
    determination of area under curve

  20. anti-CYT107 antibodies [ Time Frame: day 1, day 29 or hospital discharge, day 90 and day 180 if previous sample positive ]
    Quantification of circulating anti-CYT107 antibodies



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A written, signed informed consent, by the patient or the patient's legally authorized representative
  2. Participants with an absolute lymphocyte count (ALC) ≤ 900 cells/mm3, at two time points at least twelve hours apart, following diagnosis of vasopressor dependent sepsis and,

    1. the second time point should not be performed earlier than 48 hours after sepsis diagnosis,
    2. study drug treatment initiation is required no later than 120 hours (up to 5 days) after the last qualifying ALC ≤ 900 cells/mm3 measure, and
    3. the average value of the two qualifying ALC counts will serve as a baseline to express the percent increase at day 29, or at hospital discharge.
  3. Patients in the ICU with onset of vasopressor dependent sepsis defined as hypotension requiring treatment with any vasopressor(s) for at least 6 hours to maintain a systolic pressure ≥ 90 mmHg or a mean arterial pressure ≥65 mmHg AND at least 1 of the 2 organ dysfunction criteria below:

    1. Acute respiratory failure defined as the need for invasive mechanical ventilation for at least 24 hours to support pulmonary function
    2. Acute kidney injury defined as creatinine > 2.0 mg/dL (based on new abnormal result following onset of sepsis) OR urine output < 0.5 mL/kg/hr for > 4 hours despite adequate fluid resuscitation. In the presence of pre-existing impairment of renal function (defined as a serum creatinine concentration >2 times the upper limit of the normal reference range prior to the onset of sepsis), the patient must meet the other organ dysfunction criteria.
  4. Anticipated hospital duration of up to approx. three weeks after initiating study drug treatment to allow 6 study drug administrations (Days 18 or 19 would be final dose)
  5. This study permits the re-enrollment of a participant who may have been discontinued as a pre-treatment screen failure and/or prior to study drug treatment.
  6. Age and reproductive status:

    1. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment
    2. Women must not be breastfeeding
    3. Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with CYT107 plus 5 half-lives of CYT107 (the terminal half-life of CYT107 is up to 2 days) plus 30 days (duration of ovulatory cycle) for a total of 2 months post-treatment completion.
    4. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with CYT107 plus 5 half-lives of CYT107 plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.
    5. Azoospermic males are exempt from contraceptive requirements.
    6. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements but still must undergo pregnancy testing.

Exclusion Criteria:

  1. Cancer with current chemotherapy or radiotherapy (receipt of chemotherapy or radiotherapy for cancer within the last 6 weeks). All patients with current, or history of, hematologic malignancy (including, but not limited to, ALL, AML, CLL, CML, etc.) or lymphoma will be excluded, regardless of receipt of recent chemotherapy
  2. Patients with minimal chance of survival and life expectancy less than 3-5 days as defined by an APACHE II score of ≥ 35 at time of consideration for study eligibility
  3. Patients with history or current evidence of autoimmune disease including for example: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosus, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc.
  4. Patients who have received a solid organ transplant or bone marrow transplant.
  5. Patients with active or a history of acute or chronic lymphocytic leukemia
  6. AIDS-defining illness (category C) diagnosed within the last 12 months prior to study entry
  7. Known history of chronic HBV infection and not on treatment with HBV nucleoside analogues prior to the current hospitalization or HBV DNA > 100 IU/mL
  8. Known history of infection with HCV and currently undergoing treatment for HCV infections or has detectable HCV RNA
  9. Known history of tuberculosis and currently undergoing treatment for tuberculosis
  10. History of splenectomy
  11. Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
  12. Participation in another investigational interventional study testing a drug or a medical device within the last 3 months prior to study entry
  13. Patients receiving immunosuppressive drugs, e.g., TNF-alpha inhibitors, for any reason, or systemic corticosteroids other than hydrocortisone at a dose of 300 mg/day
  14. Patients receiving concurrent immunotherapy or biologic agents; including growth factors, cytokines and interleukins other than the study medication : IL-2, Interferons α, β and γ, GM-CSF, G-CSF, HIV vaccines, immunosuppressive drugs, hydroxyurea, immunoglobulins, adoptive cell therapy
  15. Prior exposure to IL 7 or other drugs specifically targeting T cells
  16. Presence of an advanced directive to withhold or withdraw life-sustaining treatment, DNR order or no CPR order, or comfort measures only order
  17. Patients for whom prognosis is poor and source control of septic event is considered unlikely per the clinical and research teams.
  18. Patients under guardianship

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03821038


Contacts
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Contact: Michel MORRE, DVM +33603357060 mmorre@revimmune.com
Contact: Jane BLOOD, CRN 314-747-5531 bloodj@anest.wustl.edu

Locations
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United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610-0108
Contact: Scott Brakenridge, MD    352-273-5670    Scott.Brakenridge@surgery.ufl.edu   
Contact: Jennifer Lanz, RN, ARNP    3522735497    Jennifer.Lanz@surgery.ufl.edu   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Richard Hotchkiss, MD    314-362-8552    richardshotchkiss@wustl.edu   
Contact: Jane Blood, RN,BS    314-747-5531    jblood@wustl.edu   
France
CHU Angers Recruiting
Angers, France, 49933
Contact: Pierre ASFAR, MD    02.41.35.38.15    PiAsfar@chu-angers.fr   
Contact: Marc PIERROT, MD    0033 2.41.35.38.45    mapierrot@chu-angers.fr   
Hopital HENRI MONDOR Recruiting
Créteil, France, 94300
Contact: Nicolas DE PROST, MD    33149812394    nicolas.de-prost@aphp.fr   
Contact: Armand MEKONTSO DESSAP, MD    33149812391    armand.dessap@aphp.fr   
CHU Dijon Bourgogne Recruiting
Dijon, France, 21000
Contact: Jean Pierre QUENOT, MD    03 80 28 13 03    jean-pierre.quenot@chu-dijon.fr   
Contact: Pascal ANDREU, MD    03 80 28 13 03    pascal.andreu@chu-dijon.fr   
University Hospital of Limoges Recruiting
Limoges, France, 87042
Contact: Bruno FRANCOIS, MD    33 (0)5 55 05 62 74    bruno.francois@chu-limoges.fr   
Contact: Thomas Daix, MD    33 (0)5 55 05 62 74    thomas.daix@chu-limoges.fr   
Hôpital Edouard Herriot Recruiting
Lyon, France, 69003
Contact: Thomas RIMMELE, MD    33472111196 ext 33472111196    thomas.rimmele@chu-lyon.fr   
Contact: Jean-François CARABALONA, MD    33472111196 ext 33472111196    jean-francois.carabalona@chu-lyon.fr   
Chr Orleans Recruiting
Orleans, France, 45067
Contact: Thierry BOULAIN, MD    0033 238514446    thierry.boulain@chr-orleans.fr   
Contact: Mai-Anh NAY, MD    0033 238514446    mai-anh.nay@chr-orleans.fr   
Hopital COCHIN Recruiting
Paris, France, 75014
Contact: Jean Paul MIRA, MD    33 (1) 58 41 25 17    jean-paul.mira@aphp.fr   
Contact: Paul JAUBERT, MD    33 (1) 58 41 25 17    paul.jaubert@aphp.fr   
Chru Bretonneau Recruiting
Tours, France, 37044
Contact: Pierre-Francois DEQUIN, MD    02-47-47-38-55    pierre-francois.dequin@univ-tours.fr   
Contact: Antoine GUILLON, MD    02-47-47-38-55    antoine.guillon@univ-tours.fr   
Sponsors and Collaborators
Revimmune
Washington University School of Medicine
University Hospital, Limoges
George Clinical Pty Ltd
Investigators
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Principal Investigator: Richard Hotchkiss, MD Washington University School of Medicine
Principal Investigator: Bruno François, MD Limoges Hospital
Publications:
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Responsible Party: Revimmune
ClinicalTrials.gov Identifier: NCT03821038    
Other Study ID Numbers: IRIS-7-C&D
First Posted: January 29, 2019    Key Record Dates
Last Update Posted: November 7, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Study results will be published Individual data can't be shared and are protected by the new GDPR rule

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Revimmune:
Sepsis
IL-7
lymphocytopenia
Additional relevant MeSH terms:
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Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes