A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection in UK
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 35
- 试验地点
- 12
- 主要终点
- Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whicheve
研究概览
简要总结
Comparison of the effects of CYT107 vs Placebo administered IM at 10µg/kg twice a week for two weeks on immune reconstitution of lymphopenic COVID-19 patients.
详细描述
Approximately forty-eight (48) participants will be randomized 1:1 to receive (a) Intramuscular (IM) administration of CYT107 at 3 μg/kg followed, after 48hrs of observation, by 10 μg/kg twice a week for 2 weeks or (b) Intramuscular (IM) placebo (normal saline) at the same frequency. An interim safety review will take place after the first 12 patients. If the CYT107 is well tolerated, the test dose (3 μg/kg) will cease and that initial dose will become the same as the rest of the doses (10 μg/kg). So, the remaining patients will be randomized to receive 5 administrations of (a) CYT107 at 10 μg/kg every 3 to 4 days for 2 weeks or (b) Intramuscular (IM) placebo (normal saline) at the same frequency.
The aim of the study is to test the ability of CYT107 to produce an immune reconstitution of these patients and observe possible association with a clinical improvement
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)
盲法说明
Double blind
入排标准
- 年龄范围
- 25 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A written, signed informed consent, or emergency oral consent, by the patient or the patient's legally authorized representative, and the anticipated ability for participant to be re-consented in the future for ongoing Study participation
- •Men and women aged ≥ 25 - 80 (included) years of age
- •Hospitalized patients with one absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, collected at baseline or no more than 72h before baseline
- •Hospitalized patients with moderate to severe hypoxemia requiring oxygen therapy at >2L per minute nasal cannula or greater to keep saturations >90%, non-invasive positive pressure ventilation (e.g., BIPAP), or patients intubated/ventilated for respiratory failure
- •Confirmed infection with COVID-19 by any acceptable test available/utilized at each site
- •Private insurance or government support (through NHS or other)
排除标准
- •Pregnancy or breast feeding;
- •Refusal or inability to practice contraception regardless of the gender of the patient;
- •ALT and/or AST > 5 x ULN
- •Known, active auto-immune disease;
- •Ongoing cancer treatment with chemotherapy / immunotherapy or any cancer therapy within last 3 months and/or ongoing;
- •Patients with past history of Solid Organ transplant.
- •Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load.
- •Patients whose respiratory condition is showing significant deterioration as indicated by:
- •requirement for a persistent and sustained increase in inspired oxygen concentrations of 20% or more over the past 24 hours to maintain SpO2 at greater than or equal to 88% (this 20 % limit does not apply to O2 delivered by nasal canula)
- •or need for invasive mechanical ventilation
- •Patients with chronic kidney dialysis
- •Patients showing an increase of the NEWS2 score by more than 6 points during the screening / baseline period (48 to 72 hrs prior to first administration)
- •Patients with a SOFA score ≥ 9 at baseline
- •Patients with a BMI > 40
- •Patients with baseline Rockwood Clinical Frailty Scale ≥ 6.(assessed as patient or proxy 4-week recall of chronic health and frailty status prior to COVID infection)
- •Patients under guardianship
研究组 & 干预措施
CYT107
Intra-muscular administration of CYT107 twice a week for a total of 5 administrations
干预措施: Interleukin-7 (Drug)
Saline
Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations
干预措施: Placebos (Drug)
结局指标
主要结局
Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whicheve
时间窗: 1 month
A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
次要结局
- To compare the effect of CYT107 versus placebo on readmissions to ICU(45 days)
- To track and evaluate other known biomarkers of inflammation: CRP(30 days)
- To compare the effect of CYT107 versus placebo on the length of hospitalization(45 days)
- To assess the impact of CYT107 on all-cause mortality through day 45(45 days)
- To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45(45 days)
- To compare the effect of CYT107 versus placebo on the length of stay in ICU(45 days)
- To track and evaluate other known biomarkers of inflammation: Ferritin(30 days)
- determine if CYT107 will lead to a significant decline of SARS-CoV-2 viral load through day 30 or HD(one month)
- To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45(45 days)
- To determine the effect of CYT107 on CD4+ and CD8+ T cell counts(30 days)
- To track and evaluate other known biomarkers of inflammation: D-dimer(30 days)
- To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.(1 month)
- To compare the effect of CYT107 versus placebo on organ support free days(45 days)
- Evaluation of physiological status through NEWS2 score(30 days)