A Randomized, Placebo-controlled, Double-blind, Multi-center, Phase III Trial to Assess the Efficacy and Safety of Trimodulin (BT588) in Hospitalized Subjects With Severe Community-acquired Pneumonia (sCAP)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Biotest
- 入组人数
- 590
- 试验地点
- 410
- 主要终点
- 28-day all-cause mortality rate
研究概览
简要总结
The main objective of the trial is to assess the efficacy and safety of trimodulin as adjunctive treatment to standard of care (SoC) compared to placebo plus SoC in hospitalized subjects with sCAP on invasive mechanical ventilation (IMV).
Other objectives are to determine detailed pharmacokinetic (PK) properties of trimodulin in a PK substudy and to determine its pharmacodynamic (PD) properties.
详细描述
This is a randomized, placebo-controlled, double-blind, multi-center, multi-national, phase III trial, to assess the efficacy and safety of trimodulin compared to placebo treatment, as adjunctive treatment to SoC in hospitalized subjects with sCAP receiving IMV.
Subjects will be randomized on a 1:1 basis to receive trimodulin or placebo, stratified by center. Investigational medicinal product (IMP) treatments will be blinded.
Subject will be administered IMP once daily on 5 consecutive days (day 1 through day 5) adjunctive to SoC. The subsequent follow-up phase comprises maximally 23 days (day 6 through day 28) followed by an end-of-follow-up visit/telephone call on day 29 [+3]. For subjects still in the hospital (trial site) after day 29, an extended follow-up is conducted until discharge or until day 90. For all subjects alive on day 29, a closing visit/telephone call on day 91 [+10] will be done.
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
All bottles will be indistinguishable.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria:
- •Written informed consent.
- •Hospitalized, adult (≥ 18 years of age) subject; In US only: ≥ 12 years of age
- •Signs of inflammation based on C-reactive protein threshold level.
- •Diagnosis of active community-acquired pneumonia (CAP) before hospital-admission or within 48 hours after admission.
- •Radiological (or other imaging technology) evidence consistent with active pneumonia.
- •Acute respiratory failure requiring IMV.
排除标准
- •For an incapacitated subject: any indication that the subject's presumed will would be against inclusion in the trial.
- •Pregnant or lactating women.
- •Subjects of childbearing potential not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment.
- •Subjects on ECMO at start of IMP treatment.
- •Suspected hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP).
- •Subjects discharged from hospital within the previous 14 days.
- •Defined neutrophil counts up to one calendar day prior to start of IMP treatment.
- •Defined platelet counts up to one calendar day prior to start of IMP treatment.
- •Defined hemoglobin within up to one calendar day prior to start of IMP treatment.
- •Pre-existing hemolytic disease.
- •Thromboembolic events (TEEs) caused by other reasons than the current sCAP within 3 months before start of IMP treatment unless the risk for further TEEs can be adequately managed with standard prophylaxis or treatment.
- •Severe renal impairment prior to start of IMP treatment.
- •End-stage renal disease (ESRD) or known primary focal segmental glomerulosclerosis (FSGS).
- •Pre-existing severe lung diseases concomitant to current sCAP (e.g. active tuberculosis, active lung cancer).
- •Pre-existing decompensated heart failure.
- •Pre-existing severe hepatic cirrhosis (Child Pugh score ≥ 10 points), or severe hepatic impairment (Child Pugh score ≥ 10 points), or hepatocellular carcinoma.
- •Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin / placebo.
- •Selective immunoglobulin A (IgA) deficiency with known antibodies to IgA.
- •Life expectancy of less than 90 days, according to the investigator's clinical judgment, because of medical conditions related neither to sCAP nor to sCAP-associated septic conditions.
- •Morbid obesity with high body mass index (BMI) ≥ 40 kg/m2, or malnutrition with low BMI < 16 kg/m
- •Treatment with polyvalent immunoglobulin preparations during the last 21 days before start of IMP treatment.
- •Known treatment with predefined medications, during the last 2 days before start of IMP treatment.
- •Hematopoietic stem cell transplantation or previous lung transplantation.
- •Treatment with investigational medications/procedures not according to SoC of the trial site, due to participation in another interventional clinical trial within 30 days before start of IMP treatment, or previous treatment with IMP in this clinical trial.
研究组 & 干预措施
Placebo
Human albumin 1%
干预措施: Placebo (human albumin 1%) (Drug)
Trimodulin
Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.
干预措施: Trimodulin (Drug)
结局指标
主要结局
28-day all-cause mortality rate
时间窗: Between days 1-29
Percentage of subjects that died until day 29 regardless of cause of death
次要结局
- Proportion of subjects in ICU on days 7, 14, 21 and 29(On days 7, 14, 21, 29)
- Ventilator-free days (VFD) until day 29(Until day 29)
- Time to discharge from hospital(Until day 91)
- Time to discharge from ICU(Until day 91)
- 90-day all-cause mortality rate(Between days 1-91)
- Rate of unscheduled return(s) to the emergency department or primary physician between day 29 and day 91(Between Days 29 - 91)
- Proportion of subjects in hospital on days 7, 14, 21 and 29(On days 7, 14, 21, 29)
- Dose modifications(Day 1-5)
- Change over time in electrocardiogram (ECG) parameters(Days -1, 1, 3, 5 and once between days 8-13)
- 28-day readmission rate(Day 29)
- Number and changes in observed Adverse Events in clinical laboratory parameters over time(Days -1, 1-5, 7, 14, 21, 29)
- Health status based on Clinical Frailty Scale (CFS) on day 91(Between Days 29 - 91)
- Days of hospitalization up to day 29(Up to day 29)
- Time to return to normal activities up to day 91(Up to day 91)
- Deterioration rate (up to day 29)(Up to day 29)
- Change in Sequential Organ Failure Assessment (SOFA) score from baseline to day 7(Between baseline and Day 7)
- Proportion of subjects with clinical cure of pneumonia up to day 29(Up to day 29)
- Days of invasive mechanical ventilation (IMV) up to day 29(Up to day 29)
- Days with oxygen supply up to day 29(Up to day 29)
- Proportion of subjects with oxygen supply on days 7, 14, 21 and 29(On days 7, 14, 21 and 29)
- Days in intensive care unit (ICU) up to day 29(Up to day 29)
- Adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest (AESIs), infusional TEAEs, TEAEs that led to permanent discontinuation of IMP and/or discontinuation of trial(Up to day 29)
- Infusion-related TEAEs(Up to day 91)
- Serious adverse events (SAEs)(Up to day 29)
- Number and changes in observed Adverse Events in vital signs over time(Days -1, 1-5, 7, 14, 21, 29)