A Multicenter, Randomized, Double-blinded, Placebo-controlled Study of IL-7 to Restore Absolute Lymphocyte Counts in Sepsis Patients
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 16
- 试验地点
- 3
- 主要终点
- White blood count
研究概览
简要总结
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-7A (Immune Reconstitution of Immunosuppressed Sepsis patients).
A parallel study will be performed in United State of America to allow a common statistical analysis of the primary end points and analysis for the enrolled patient population.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of age ≥ 18 yrs and older but < 80 yrs
- •Patients with persistent suspected sepsis at 48-120 hrs after admission
- •Two or more criteria for the systemic inflammatory response syndrome (SIRS) (see reference #19 for SIRS criteria) and a clinically or microbiologically suspected infection.
- •At least one organ failure as defined by a SOFA score of ≥2 at any time point during the 48-120 hrs after admission to the ICU
- •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.
- •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.
- •Predicted length of stay in the ICU of up to two weeks after starting drug therapy treatment in the trial
- •Ability to obtain a signed informed consent from patient or LAR consent.
排除标准
- •Cancer with current chemotherapy or radiotherapy and/or .receipt of chemotherapy or radiotherapy within the last 6 weeks
- •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
- •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.
- •Patients who have received 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
- •History of splenectomy
- •Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
- •Pregnant or lactating women
- •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.
- •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
- •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
研究组 & 干预措施
CYT107 high frequency
Patients will receive Interleukin-7 (CYT107 liquid solution) at 10µg/kg twice a week for 4 weeks
干预措施: Interleukin-7 (Drug)
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
干预措施: Interleukin-7 (Drug)
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
干预措施: Placebo (Drug)
Control
Patients will receive Placebo (NaCl 0.9%) twice a week for 4 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
White blood count
时间窗: day 1 to Day 42
Number of patients with absolute lymphocyte counts (Multiply the Lymphocytes percentage above by the total number White Blood Count) increased by more than 50% from baseline at Day 42 Kinetic of immune restoration through weekly measures of Absolute Lymphocyte Counts
Incidence of treatment-Emergent Adverse Events
时间窗: Day 1 to Day 42
Clinical occurrence of adverse events (AEs) and serious adverse events (SAEs) during the duration of the study period ending day 42, as assessed by DAIDS (2.0)
Mortality
时间窗: Day 360
lymphocyte percentage
时间窗: Day 1 to Day 42
Number of patients with absolute lymphocyte counts (Multiply the Lymphocytes percentage above by the total number White Blood Count) increased by more than 50% from baseline at Day 42 Kinetic of immune restoration through weekly measures of Absolute Lymphocyte Counts
次要结局
- CYT107 Pharmacokinetic AUC(Day 1 and Day 22)
- CYT107 Pharmacokinetic half life(Day 1 and Day 22)
- CYT107 Pharmacokinetic Cmax(Day 1 and Day 22)
- Quantification of positive binding antibodies against CYT107(Day 1, Day 11, Day 22, Day 60, Day 180 and Day 360)
- Incidence of hospital acquired secondary infections(Day 42)
- SOFA score(Day 0 Day 4, Day 8, Day 15, Day 22, Day 29)
- Specific CYT107 neutralizing antibodies(Day 1, Day 11, Day 22, Day 60, Day 180 and Day 360)
- APACHE II score(Day 0, Day 4, Day 8, Day 15, Day 22, Day 29)
- CYT107 Pharmacodynamic(Day 1, Day 8, Day 15, Day 22, Day 29)