Status:
TERMINATED
Recombinant Interleukin-7 (CYT107) to Restore Absolute Lymphocyte Counts in Sepsis Patients
Lead Sponsor:
Revimmune
Collaborating Sponsors:
Washington University School of Medicine
University Hospital, Limoges
Conditions:
Sepsis, Severe
Eligibility:
All Genders
18-85 years
Phase:
PHASE2
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 reconstitutio...
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 o...
Eligibility Criteria
Inclusion
- A written, signed informed consent, by the patient or the patient's legally authorized representative
- 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,
- the second time point should not be performed earlier than 48 hours after sepsis diagnosis,
- 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
- 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.
- 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:
- Acute respiratory failure defined as the need for invasive mechanical ventilation for at least 24 hours to support pulmonary function
- 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.
- 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)
- 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.
- Age and reproductive status:
- 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
- Women must not be breastfeeding
- 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.
- 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.
- Azoospermic males are exempt from contraceptive requirements.
- WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements but still must undergo pregnancy testing.
Exclusion
- 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
- 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
- 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.
- Patients who have received a solid organ transplant or bone marrow transplant.
- Patients with active or a history of acute or chronic lymphocytic leukemia
- AIDS-defining illness (category C) diagnosed within the last 12 months prior to study entry
- 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
- Known history of infection with HCV and currently undergoing treatment for HCV infections or has detectable HCV RNA
- Known history of tuberculosis and currently undergoing treatment for tuberculosis
- History of splenectomy
- Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
- Participation in another investigational interventional study testing a drug or a medical device within the last 3 months prior to study entry
- 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
- 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
- Prior exposure to IL 7 or other drugs specifically targeting T cells
- Presence of an advanced directive to withhold or withdraw life-sustaining treatment, DNR order or no CPR order, or comfort measures only order
- Patients for whom prognosis is poor and source control of septic event is considered unlikely per the clinical and research teams.
- Patients under guardianship
Key Trial Info
Start Date :
June 1 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 6 2021
Estimated Enrollment :
21 Patients enrolled
Trial Details
Trial ID
NCT03821038
Start Date
June 1 2019
End Date
October 6 2021
Last Update
October 27 2021
Active Locations (10)
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1
University of Florida
Gainesville, Florida, United States, 32610-0108
2
Washington University School of Medicine
St Louis, Missouri, United States, 63110
3
CHU Angers
Angers, France, 49933
4
Hopital HENRI MONDOR
Créteil, France, 94300