A Randomized, Placebo-controlled, Double-blind, Multi-center, Phase III Trial to Assess the Efficacy and Safety of Trimodulin (BT588) in Adult Hospitalized Subjects With CAP Including COVID-19 Pneumonia.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Biotest
- 入组人数
- 107
- 试验地点
- 64
- 主要终点
- Composite Endpoint
研究概览
简要总结
The main objectives of the trial are to assess the efficacy and safety of trimodulin as adjunctive treatment to standard of care (SoC) compared to placebo plus SoC in adult hospitalized subjects with non-severe community-acquired pneumonia (CAP) or moderate / severe Coronavirus Disease 2019 (COVID-19) pneumonia.
Other objectives are to determine pharmacokinetic (PK) and pharmacodynamic (PD) properties of trimodulin.
详细描述
This is a randomized, placebo-controlled, double-blind, multi-center, phase III trial to assess the efficacy and safety of trimodulin compared to placebo treatment, adjunctive to SoC in adult hospitalized subjects with non-severe community-acquired pneumonia (CAP) or moderate / severe Coronavirus Disease 2019 (COVID-19) pneumonia. Patients requiring low-flow oxygen, non-invasive ventilation or high-flow oxygen and with signs of early systemic inflammation (defined by C reactive protein (CRP), D-dimer and platelet levels) will be enrolled.
Subjects will be randomized to receive either trimodulin or placebo on a 1:1 basis, stratified by type of oxygen supply before randomization and by region. Investigational Medicinal Product (IMP) treatments will be blinded. Subjects will be administered IMP once daily on five 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 all subjects still in the hospital after day 29, an extended follow-up visit is conducted until day 90 or until discharge. For all subjects a closing visit/telephone call on day 91 [+10] will be done.
For the evaluation of the primary and several secondary endpoints of the trial, a 9-category ordinal scale will be used. The primary objective is to assess efficacy of trimodulin based on clinical deterioration and mortality to demonstrate superiority to treatment with placebo. Secondary objectives are to assess efficacy and safety and to determine PK and PD properties of trimodulin compared to placebo.
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
- •Written informed consent.
- •Hospitalized, adult (≥ 18 years of age) subjects.
- •Diagnosis of CAP or COVID- 19 pneumonia (e.g. according to local guidelines) and with radiologic evidence showing new pulmonary lobar or multilobar infiltrates consistent with CAP or COVID-19 pneumonia.
- •Receiving oxygen supply via low-flow oxygen, high-flow oxygen or on non-invasive ventilation.
- •Fulfilling at least one clinical respiratory parameter (SpO2 ≤ 94% and/or 100 mm Hg < PaO2/FiO2 ≤ 300 mm Hg).
- •Signs of early systemic inflammation based on CRP and coagulation parameter threshold levels.
排除标准
- •Pregnant or lactating women.
- •Subject on invasive mechanical ventilation and/or extracorporeal membrane oxygenation.
- •Subject with septic shock and in need for vasopressors.
- •Severe neutropenia prior to start of treatment.
- •Hemoglobin >7 g/dL prior to start of treatment.
- •Pre-existing hemolytic disease.
- •Pre-existing thromboembolic events (TEEs).
- •Subject on dialysis or with severe renal impairment prior to start of treatment.
- •Subject with end stage renal disease, or known primary focal segmental glomerulosclerosis.
- •Pre-existing severe lung diseases to current pneumonia.
- •Pre-existing decompensated heart failure.
- •Pre-existing hepatic cirrhosis, severe hepatic impairment , or hepatocellular carcinoma.
- •Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin/placebo.
- •Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA.
- •Known human immunodeficiency virus infection.
- •Life expectancy of less than 90 days.
- •Morbid obesity or malnutrition.
- •Treatment with predefined medications (certain immune modulators or immunosuppressants) before entering the trial.
研究组 & 干预措施
Trimodulin
Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.
干预措施: Trimodulin (Drug)
Placebo
Human albumin 1%
干预措施: Placebo (human albumin 1%) (Drug)
结局指标
主要结局
Composite Endpoint
时间窗: Until day 29
Composite of percentage of subjects with a change of at least 1 category on the 9-category ordinal scale from baseline (between days 6-29) and 28-day all-cause mortality rate (between days 1-29)
次要结局
- Proportion of subjects improved, unchanged, and deteriorated/died(Between days 1-29)
- 28-days all-cause mortality rate(Day 29)
- Proportion of subjects in ICU(Day 29)
- All adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest (AESIs), infusional TEAEs, TEAEs that led to permanent withdrawal of IMP and/or discontinuation of trial(Until day 29)
- 90-days all-cause mortality rate(Day 91)
- Days of invasive mechanical ventilation (IMV)/ extracorporeal membrane oxygenation (ECMO)(Day 29)
- Days in intensive care unit (ICU)(Day 29)
- Dose modifications(Day 1-5)
- Changes over time in clinical laboratory parameters(Days -1, 1-5, 7,14, 21, 29)
- Proportion of subjects on IMV/ECMO(Day 29)
- Proportion of subjects with oxygen supply(Days 7, 14, 21, 29)
- TEAEs(Until day 29)
- Clinical deterioration rate(Between days 6-29 and days 1-29)
- Time to recovery(Between days 1-29)
- Proportion of subjects with score ≤ 2(Day 29)
- Proportion of subjects with different partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) ratios(Days 7, 14, 21, 29)
- Days with oxygen supply(Day 29)
- Days of hospitalization(Day 29)
- SAEs(Until day 29)
- Change over time in ECG parameters(Days -1, 1, 3, 5 and once between days 8-13)
- Changes over time in vital signs(Days -1,1-3, 5, 7 ,14, 21, 29)