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Trial record 1 of 10 for:    il-7 in sepsis
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A Study of IL-7 to Restore Absolute Lymphocyte Counts in Sepsis Patients (IRIS-7-B)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02640807
Recruitment Status : Completed
First Posted : December 29, 2015
Results First Posted : July 9, 2020
Last Update Posted : July 9, 2020
Sponsor:
Collaborators:
Vanderbilt University School of Medicine
Washington University School of Medicine
Information provided by (Responsible Party):
Revimmune

Brief Summary:

A multicenter, randomized, double-blinded, placebo-controlled study of two dosing frequencies of recombinant Interleukin-7 (CYT107) treatment to restore absolute lymphocyte counts in sepsis patients; IRIS-7B (Immune Reconstitution of Immunosuppressed Sepsis patients).

A parallel study will be performed in France to allow a common statistical analysis of the primary end points and analysis for the enrolled patient population.


Condition or disease Intervention/treatment Phase
Severe Sepsis With Septic Shock Drug: Interleukin-7 Drug: Placebo Phase 2

Detailed Description:

Sepsis is the leading cause of death in critically ill patients in most intensive care units in Europe and the US. Recently, evidence has accumulated that sepsis progresses from a state of hyper-inflammation to a state of immunosuppression. This immunosuppressive phase is characterized by increased incidence of secondary infections often with relatively avirulent opportunistic type pathogens. Currently, new therapeutic approaches to sepsis are occurring using immuno-adjuvants that boost host immunity. One of the most promising agents Interleukin-7 is an essential, non-redundant, pluripotent cytokine produced mainly by bone marrow and thymic stromal cells that is required for T-cell survival.In addition to its anti-apoptotic properties, IL-7 induces potent proliferation of naïve and memory T-cells potentially supporting replenishment of the peripheral T-cell pool which is severely depleted during sepsis. These effects were confirmed in clinical trials at the National Cancer Institute and in HIV+ patients.

This clinical study will test the ability of IL-7 to restore the absolute lymphocyte counts in septic patients who have markedly reduced levels of circulating lymphocytes. An effect already confirmed in preclinical models of sepsis.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blinded, Placebo-controlled Study of Two Dosing Frequencies of Recombinant Interleukin-7 (CYT107) Treatment to Restore Absolute Lymphocyte Counts in Sepsis Patients.
Study Start Date : January 2016
Actual Primary Completion Date : August 27, 2018
Actual Study Completion Date : August 27, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: CYT107 high frequency
Patients will receive Interleukin-7 (CYT107 liquid solution) at 10µg/kg twice a week for 4 weeks
Drug: Interleukin-7
IM (intra-muscular) administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR (International Normalized Ratio) >2.5 or platelet count < 35,000
Other Name: CYT107

Experimental: CYT107 low frequency
Patients will receive Interleukin-7 (CYT107 liquid solution) at 10µg/kg twice a week for the first week, followed by CYT107 and Placebo once a week for the three following weeks
Drug: Interleukin-7
IM (intra-muscular) administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR (International Normalized Ratio) >2.5 or platelet count < 35,000
Other Name: CYT107

Drug: Placebo
IM administration of Placebo (SC administration for patients with INR>2.5 or platelet count < 35,000
Other Name: NaCl 0.9%

Placebo Comparator: Control
Patients will receive Placebo (NaCl 0.9%) twice a week for 4 weeks
Drug: Placebo
IM administration of Placebo (SC administration for patients with INR>2.5 or platelet count < 35,000
Other Name: NaCl 0.9%




Primary Outcome Measures :
  1. Immune Reconstitution of Lymphocytopenic Sepsis Patients [ Time Frame: Day 0 to 42 ]

    Number of patients showing an increase of Absolute Lymphocyte Count >50% from baseline at Day 42.

    Kinetic of immune restoration through weekly measures of Absolute Lymphocyte Counts



Secondary Outcome Measures :
  1. CYT107 Effect on Absolute Lymphocyte Count [ Time Frame: Day 42 ]
    Number of Patients with Absolute Lymphocyte Count > 1.2 at Day 42

  2. CYT107 Immunogenicity [ Time Frame: Day 60 ]
    number of patients with binding or neutralizing antibodies against CYT107 at Day 60



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients of age ≥ 18 yrs and older but < 80 yrs
  2. Patients with persistent suspected sepsis at 48-120 hrs after admission
  3. Two or more criteria for the systemic inflammatory response syndrome (SIRS) (see reference #19 for SIRS criteria) and a clinically or microbiologically suspected infection.
  4. At least one organ failure as defined by a SOFA (Sepsis-related organ failure assessment) score of ≥2 at any time point during the 48-120 hrs after admission to the ICU
  5. Requirement of vasopressor treatment as follows: i) epinephrine or norepinephrine at ≥ 0.05 µg/kg/min ideal body weight; ii) vasopressin, or iii) dopamine at ≥ 4-5 μg/kg/min ideal body weight, continuously for 4 hrs or more, provided that at least 20 ml/kg of ideal body weight of crystalloid or an equivalent volume of colloid was administered during the 24-hour interval surrounding the start of vasopressor treatment, to maintain systolic pressure ≥ 90 mmHg or a mean arterial pressure ≥ 60 mmHg at any time point during their sepsis course preceding enrollment into the IL-7 study.
  6. Lymphopenia with an absolute lymphocyte count ≤ 900 cells/mm3 at either the day of consent or the day prior to consent during their ICU stay.
  7. Predicted length of stay in the ICU of up to two weeks after starting drug therapy treatment in the trial (ICU may also include a close medical ward on the same study site where the patient will remain under medical control of the Investigator).
  8. Ability to obtain a signed informed consent from patient or LAR (Legally Authorized Representative) consent.

Exclusion Criteria:

  1. Cancer with current chemotherapy or radiotherapy and/or .receipt of chemotherapy or radiotherapy within the last 6 weeks
  2. Cardiopulmonary resuscitation within the previous 4 weeks without objective evidence of full neurologic recovery) or patients who have minimal chance of survival and are not expected to live > 3-5 days as defined by an APACHE II score of ≥ 35 at time of consideration for study eligibility
  3. Patients with a history of or who currently have evidence of autoimmune disease including for example: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosis, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc.
  4. Patients who have received 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. History of splenectomy
  8. Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
  9. Pregnant or lactating women
  10. Participation in another investigational interventional study within the last 6 months prior to study entry, with the exception of studies aimed at testing sedation products belonging to standard of care such as Propofol, Dexmedetomidine, Midazolam.
  11. Patients receiving immunosuppressive drugs, e.g., TNF-alpha inhibitors, for rheumatoid arthritis, inflammatory bowel disease or any other reason, or systemic corticosteroids other than hydrocortisone at a dose of 300 mg/day
  12. Patients receiving concurrent immunotherapy or biologic agents including: growth factors, cytokines and interleukins, (other than the study medication); for example IL-2,growth factors, interferons, HIV vaccines, immunosuppressive drugs, hydroxyurea, immunoglobulins, adoptive cell therapy
  13. Prisoners

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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): NCT02640807


Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212-1050
Sponsors and Collaborators
Revimmune
Vanderbilt University School of Medicine
Washington University School of Medicine
Investigators
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Principal Investigator: Edward SHERWOOD, MD, PhD Vanderbilt University Medical Center
Study Director: Richard HOTCHKISS, MD, PhD Washington University School of Medicine
  Study Documents (Full-Text)

Documents provided by Revimmune:
Study Protocol  [PDF] December 14, 2015
Statistical Analysis Plan  [PDF] December 14, 2015

Publications of Results:

Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Revimmune
ClinicalTrials.gov Identifier: NCT02640807    
Other Study ID Numbers: CLI-107-15
First Posted: December 29, 2015    Key Record Dates
Results First Posted: July 9, 2020
Last Update Posted: July 9, 2020
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Revimmune:
sepsis lymphocytopenia IL-7
immune reconstitution
Additional relevant MeSH terms:
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Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes