A Study of IL-7 to Restore Absolute Lymphocyte Counts in Sepsis Patients
Condition: Severe Sepsis With Septic Shock
MeSH terms: Sepsis; Toxemia
Intervention: Interleukin-7; Placebo
Intervention description: 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; IM administration of Placebo (SC administration for patients with INR>2.5 or platelet count < 35,000
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: sepsis lymphocytopenia IL-7; immune reconstitution

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.
    

Eligibility 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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