A Phase 3, multi-centre, randomised, double-blind, placebo-controlled, study to evaluate the efficacy and safety of Itolizumab in hospitalised patients with COVID-19 requiring oxygen therapy
试验速览
- 阶段
- 3 期
- 状态
- Other
- 入组人数
- 400
- 试验地点
- 10
- 主要终点
- Clinical composite endpoint comprising of:
研究概览
简要总结
This is a multi-centre, two-arm, double-blind, placebo-controlled, randomised, clinical trial to evaluate the efficacy and safety of Itolizumab in hospitalised patients with COVID-19 requiring oxygen therapy. The study consists of a Screening period (up to 2 days), Treatment period (up to 28 days from first dose of Itolizumab/placebo) and an Extended follow-up period of up to 90 days from first dose.
Patients will be screened for up to 2 days prior to Day 1 for eligibility. About 400 eligible patients will be randomised on Day 1 in a 1:1 ratio to Treatment Arm A (Itolizumab + Standard of Care) or Treatment Arm B (Placebo + Standard of Care). Randomisation will be stratified by age, by the baseline disease severity. Patients randomised to Treatment Arm A will be administered study drug Itolizumab 1.6 mg/kg (+Standard of Care) on Day 1 via IV infusion, whereas those randomised to Treatment Arm B will be administered placebo (+Standard of Care).
All patients will receive Standard of Care as per institutional practice throughout the study including whenever appropriate steroids, antithrombotics, antivirals and antimicrobials/antibiotics. Patients will be monitored for efficacy and safety through Day 28 and followed up till Day 90.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1 Male or female adults above ≥18 years.
- •2 Informed consent for participation in the study by patient or their legally acceptable representative.
- •3 Hospitalised patients with COVID-19 infection receiving systemic steroids with scores 5 or 6 on 8-point clinical scale (hospitalised and requiring supplemental oxygen / requiring non-invasive ventilation or use of high-flow oxygen devices but not on invasive mechanical ventilation) 4 An inflammatory, phenotype defined by a body temperature greater than 38 °C / 100.4 °F anytime during the last 2 days, OR increased markers of inflammation (CRP ≥ 3 ULN as per local lab) at screening.
- •5 A confirmed virological diagnosis of SARS-CoV2 infection with RT-PCR 6 Patients with no known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV).
- •7 Women of childbearing potential (WOCP) with negative pregnancy test or are not breastfeeding at screening.
- •8 Males and WOCP agreeing to use adequate contraception (e.g., double barrier contraception) for 130 days from randomisation.
排除标准
- •1 Known severe allergic reactions to monoclonal antibodies.
- •2 Has active tuberculosis or known history of inadequately treated tuberculosis or latent tuberculosis(based on the the guidance given in protocol on excluding tuberculosis patients).
- •3 Known active systemic or pulmonary bacterial, fungal or viral (other than SARS-CoV-2) infection at the time of randomisation 4 In the opinion of the investigator, progression to death is highly probable, irrespective of the provision of treatments.
- •5 Patient receiving IMV at the time of randomisation or in the opinion of investigator, progression to IMV is highly probable in next 24 hours.
- •6 Patient receiving oral anti-rejection or immune-suppressive drugs regularly in the last 3 months prior to screening.
- •7 Participating in another clinical study of an investigational product and/or received an investigational product within 30 days or within 5 half-lives prior to randomisation.
- •8 Patients treated with IL-6 inhibitors, example: tocilizumab or other biologics with anti-inflammatory action (e.g., TNF-α inhibitors, anti-IL17A) or bevacizumab or JAK inhibitors (e.g. Baricitinib, Tofacitinib) or immunoglobulin for COVID-19 including other immunomodulatory biologic drugs with a positive opinion for emergency use or for compassionate use.
- •9 Requires renal dialysis, either acute or chronic, at the time of randomisation 10 Any serious inherited disorder, medical condition or abnormality of clinical laboratory tests that, in the investigator’s judgement, precludes the patient’s safe participation in and completion of the study.
- •11 Absolute neutrophil count<1000/mm³ 12 Platelet count <50,000/mm³ 13 Absolute Lymphocyte count<500/mm³.
结局指标
主要结局
Clinical composite endpoint comprising of:
时间窗: 1. Day 1 through Day 28 | 2. Day 1 through Day 28 | 3. Day 1 through Day 28
1 Mortality at Day 28
时间窗: 1. Day 1 through Day 28 | 2. Day 1 through Day 28 | 3. Day 1 through Day 28
2 Clinical deterioration, defined as progression to a higher ordinal score from enrolment scores of 5 or 6 during the period of 28 days.
时间窗: 1. Day 1 through Day 28 | 2. Day 1 through Day 28 | 3. Day 1 through Day 28
3 Time to recovery by Day 28, defined as time to get to a score of 3 or below in the 8-point ordinalscale plus sustained recovery.
时间窗: 1. Day 1 through Day 28 | 2. Day 1 through Day 28 | 3. Day 1 through Day 28
次要结局
- 8. Change from baseline in IL-6 and TNF-α.(Baseline, 48 hours post dose, at Day 7 and then weekly until discharge)
- 4. Cumulative rate of patients alive and without IMV by Day 90 from randomisation(Day 1 through Day 90)
- 7. Time to independence from oxygen therapy in days.(from randomisation up to Day 90)
- 5. Cumulative rate of patients going to IMV by Day 90 from randomisation.(Day 1 through Day 90)
- Key Secondary Endpoint:-(Clinical composite endpoint comprising of :)
- Secondary Endpoints:-(1.Mortality by Day 28, Day 60 and Day 90.)
- 6. Duration of hospitalisation.(from randomisation up to patients discharge - Days of hospitalisation)
- 3. Proportion of patients with clinical improvement (defined as either an improvement of ≥2 points on a COVID-19 8-point ordinal scale or discharge from the hospital, whichever comes first) over time.(Day 1 through Day 90)
- 10. Incidence, nature, severity of AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) and causality of AEs.(Day 1 through Day 28 and up to Day 90)
- 9, Change from baseline in levels of inflammatory markers like CRP, serum ferritin, D-dimer and LDH.(Baseline, 48 hours post dose, at Day 7 and then weekly until discharge)