Safety and Efficacy of the Treatment of Hospitalized Patients With COVID 19 Infection With an Inhibitor of IL-4 and IL-13 Signaling: A Phase IIa Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Day 28 Ventilator Free Survival
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, superiority phase IIa trial to assess the safety and efficacy of dupilumab use in hospitalized patients with moderate to severe COVID-19 infection. Subsequently, we conducted a 1 year follow up study to investigate the occurrence of Post COVID conditions (PCC) in our study population through assessment of pulmonary function, symptoms, neurocognition and immune biomarkers to observe for any treatment group differences.
详细描述
A total of 40 eligible subject were enrolled and randomized in a 1:1 ratio to receive either dupilumab or placebo, stratifying on the disease severity measured by the required oxygen ≤ 15L or > 15L by nasal cannula. Both arms received standard of care management per current National Institutes of Health (NIH) COVID-19 treatment guideline in addition to their randomized treatments. Patients were then followed prospectively for up to 360 days after enrollment.
As an extension to the randomized double-blind placebo-controlled trial assessing dupilumab for treatment of those hospitalized with acute moderate to severe COVID-19, subjects were followed up at 1 year for evaluation of pulmonary function testing (PFT), pulmonary imaging, immune biomarkers, neurocognition and symptoms.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Male or female 18 years of age or older at the time of enrollment.
- •Patients hospitalized with a positive RT-PCR for SARS-CoV-2 within the last 14 days, with illness duration within the last 14 days, and evidence of moderate to severe COVID-19 infection as defined by NIH COVID-19 Severity Categorization (8):
- •Moderate illness: Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have saturation of oxygen SpO2≥ 94% on room air at sea level.
- •Severe illness: Individuals who have SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, respiratory frequency >30 breaths/min, or lung infiltrates >50%.
- •Patient and/or legally authorized representative is willing and able to provide written informed consent and comply with all protocol requirements.
- •Patients with hematologic malignancies or solid tumors are eligible.
- •Patients with autoimmune disorders are eligible.
- •Patients with immunodeficiency and organ or stem cell transplant recipients are eligible.
- •Patients with acute or chronic renal injury/failure are eligible.
- •Patients with neutropenia/lymphopenia are eligible.
- •Patients with elevated liver function tests are eligible.
- •Women who are not taking contraception are eligible.
- •Patients who are currently or have recently received steroids and/or remdesivir are eligible.
- •Patient agrees to not participate in another clinical trial for the treatment of COVID-19 through end of study period.
排除标准
- •Patients who do not require inpatient admission for COVID-19 infection.
- •Patients who require invasive mechanical ventilation at time of enrollment.
- •A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk due to study participation.
- •Pregnancy or breast feeding (lactating women who agree to discard breast milk from day 1 until two weeks after the last study product is given are not excluded).
- •Allergy to Dupilumab or its excipients.
- •Received any of the following in the two weeks prior to screening as treatment of COVID-19:
- •small molecule tyrosine kinase inhibitors (e.g. imatinib, gefitinib, acalabrutinib, etc.);
- •monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [or sarilumab], etc.);
- •monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19;
- •Any other immunomodulatory (other than steroids) medications within 5 half-lives or 30 days prior to randomization.
- •Current acute parasitic helminth infection or history of chronic parasitic infection.
- •History of ocular scleritis, uveitis, keratitis or recent (<6 months) eye injury (chemical or traumatic), infection or vascular occlusion.
- •Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects.
研究组 & 干预措施
Dupilimab
Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.
干预措施: Dupilumab (Biological)
Placebo
Normal saline will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28.
干预措施: Placebo (Drug)
结局指标
主要结局
Day 28 Ventilator Free Survival
时间窗: at 28 Days ± 2d
Proportion of patients alive and free of invasive mechanical ventilation
Follow up Study 1 Year Outcome: Pulmonary Function Testing- Oxygen Diffusion and 6 Minute Walk Testing
时间窗: 365 ± 90 days
Proportion of patients with abnormal diffusing capacity for carbon monoxide (DLCO) and/or 6 minute walk testing 1 year after acute COVID-19 infection.
次要结局
- Cumulative Incidence of Grade 3 and 4 Clinical Adverse Events, Serious Adverse Events (SAEs) or Death(Day 0 through Day 60)
- Change in C-reactive Protein (CRP)(Day 0 through Day 14)
- Day 28 All-cause Mortality Rate(at Day 28)
- Proportion of Patients With Eosinophilia(Day 0 through Day 60)
- Follow-up Study 1 Year Outcome: Differences in High Resolution Computed Tomography (HRCT) Chest Scan Appearance Post Recovery(365 ± 90 days)
- Change in Ferritin(Day 0 through Day 14)
- Percentage of Patients Needing Extracorporeal Membrane Oxygenation (ECMO)(Day 0 through Day 60)
- Follow-up Study 1 Year Outcome: Conduct a 6 Minute Walk Testing(365 ± 90 days)
- Follow-up Study 1 Year Outcome: Assess Neurocognitive Function Using the MOCA(365 ± 90 days)
- SARS-CoV-2 Variants(Day 0)
- Day 60 All Cause Mortality(Day 60)
- Day 60 Ventilator Free Survival(Day 60)
- Percentage of Patients Needing Renal Replacement Therapy(Day 0 through Day 60)
- Change in Plasma Total Immunoglobulin E (IgE) Levels(Day 0 and Day 14)
- Duration of Hospitalization(Day 0 through Day 30)
- Follow Up Study 1 Year Outcome: All-cause Mortality at 1 Year(365 days)
- Percentage of Patients Needing Vasopressors(Day 0 through Day 60)
- Follow up Study 1 Year Outcome: Pulmonary Function Testing- Abnormal Spirometry(365 ± 90 days)
研究者
William Petri, MD, PhD
Wade Hampton Frost Professor of Medicine and Vice Chair for Research of the Department of Medicine, and Professor of Medicine, Microbiology, Immunology and Cancer Biology, and Pathology, Medicine: Infectious Diseases and International Health
University of Virginia