Recombinant Interleukin-7 (CYT107) to Restore Absolute Lymphocyte Counts in Sepsis Patients
Recombinant Interleukin-7 (CYT107) to Restore Absolute Lymphocyte Counts in Sepsis Patients
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.
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