Interferon Lambda for Immediate Antiviral Therapy at Diagnosis (ILIAD): A Phase II Randomized, Double-blind, Placebo-controlled, Multicenter Trial to Evaluate the Effect of Peginterferon Lambda for the Treatment of COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 157
- 试验地点
- 7
- 主要终点
- Cohort A (Ambulatory) - Treatment-emergent and treatment related serious adverse events (Primary Safety Endpoint)
研究概览
简要总结
Interferon lambda is one of the main arms of the innate antiviral immune response and is critical for controlling respiratory viral infections in mice. Interferon lambda has a better side effect profile than other interferons because of the limited tissue distribution of its receptor. Peginterferon lambda is a long-acting form that has been studied extensively in human trials in viral hepatitis, confirming its safety. We propose to evaluate peginterferon-lambda in ambulatory and hospitalized patients with mild to moderate COVID-19.
详细描述
The study uses an adaptive design with initial enrolment in the Ambulatory cohort (Cohort A) followed by a safety assessment before initiation of enrolment in the Hospitalized cohort (Cohort B).
Ambulatory patients (Cohort A) with confirmed COVID-19 deemed well enough for home isolation will be randomized to receive a single subcutaneous injection of Peginterferon lambda 180µg or saline placebo prior to discharge. Patients will be followed remotely with visits for a repeat swab at Day 3 and 7 with the primary endpoint being the proportion positive for SARS-CoV-2 on Day 7.
Safety data will be reviewed by the Data Safety and Monitoring Committee after 50% of the Ambulatory cohort (n=60) has been enrolled. If the committee approves study continuation, enrolment will continue in the Ambulatory cohort (Cohort A) and will begin in the Hospitalized cohort (Cohort B).
Hospitalized patients (Cohort B) with moderate but not severe COVID-19 will be enrolled and randomized to Peginterferon lambda 180µg or saline placebo on Day 0 and 5. The primary endpoint will be clinical outcomes on the WHO ordinal scale. In addition to the primary endpoint on which the study is powered, numerous secondary endpoints will be evaluated. Samples will also be collected for ancillary studies to better understand predictors of disease severity and response to treatment.
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)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ambulatory Cohort - Treatment
to receive a single dose of peginterferon lambda 180µg SC at baseline (day 0).
干预措施: Peginterferon Lambda-1A (Drug)
Ambulatory Cohort - placebo
Patients in the arm will be given a single injection of 0.9% sodium chloride (normal saline) solution at baseline (day 0). A plastic 1 mL syringe will be prefilled by the study pharmacy. Each syringe will contain 0.5 mL (0.45 mL to match the volume of the Interferon plus 0.05 mL overfill) to allow for needle priming by the unblinded study nurse.
干预措施: placebo (Other)
Hospitalized Cohort - Treatment
To receive a dose of peginterferon lambda 180µg SC at baseline and a second dose on day 5.
干预措施: Peginterferon Lambda-1A (Drug)
Hospitalized Cohort - placebo
Patients in the arm will be given an injection of 0.9% sodium chloride (normal saline) solution at baseline (day 0). A plastic 1 mL syringe will be prefilled by the study pharmacy. Each syringe will contain 0.5 mL (0.45 mL to match the volume of the Interferon plus 0.05 mL overfill) to allow for needle priming by the unblinded study nurse. Patients will be administered a second dose of placebo on day 5.
干预措施: placebo (Other)
结局指标
主要结局
Cohort A (Ambulatory) - Treatment-emergent and treatment related serious adverse events (Primary Safety Endpoint)
时间窗: Day 0 to Day 28
The rate of treatment-emergent and treatment-related serious adverse events (SAEs)
Cohort A (Ambulatory) - Proportion swab negative at day 7 (Primary efficacy endpoint)
时间窗: At day 7
The proportion of participants with negative SARS-CoV-2 RNA on nasopharyngeal swab.
Cohort B (Hospitalized) - Ordinal Scale (Primary Efficacy Endpoint)
时间窗: At Day 14
Clinical status on an ordinal scale at Day 14
Cohort B (Hospitalized) - treatment-emergent and treatment-related serious adverse events (Primary Safety Endpoint)
时间窗: Day 0 to Day 28
The rate of treatment-emergent and treatment-related serious adverse events (SAEs)
次要结局
- Cohort B (Hospitalized) - COVID-19-related mortality (Clinical Outcome #8)(At day 28)
- Cohort A (Ambulatory) - Symptom severity scores (Clinical Outcome #2)(Day 0 to Day 7)
- Cohort A (Ambulatory) - Adverse and serious adverse events (Clinical Outcome #4)(Day 0 to Day 14)
- Cohort A (Ambulatory) - Symptoms in household contacts (Transmission Outcome #1)(Day 0 to Day 14)
- Cohort B (Hospitalized) - ICU admission (Clinical Outcome #2)(Day 0 to day 28)
- Cohort B (Hospitalized) - Change in respiratory symptom score (Clinical Outcome #5)(Day 0 to 7, Day 0 to 14, and Day 0 to 28)
- Cohort A (Ambulatory) - Hospitalization (Clinical Outcome #3)(Day 0 to Day 14)
- Cohort A (Ambulatory) - Symptom Resolution (Clinical Outcome #1)(Day 0 to Day 14)
- Cohort A (Ambulatory) - Swab negative at day 3 (Virologic/Immunological Outcome #1)(At Day 3)
- Cohort A (Ambulatory) - Correlation with interferon lambda 4 genotype (Virologic/Immunological Outcome #5)(Through day 7)
- Cohort A (Ambulatory) - COVID-19 in household contacts (Transmission Outcome #2)(At Day 30)
- Cohort B (Hospitalized) - Need for intubation (Clinical Outcome #3)(Day 0 to Day 14 and to Day 28)
- Cohort B (Hospitalized) - Length of hospital stay (Clinical Outcome #4)(Day 0 to Day 14)
- Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #16)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #15)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort A (Ambulatory) - Proportion with antibodies (Virologic/Immunological Outcome #4)(Day 0 and Day 7)
- Cohort B (Hospitalized) - All-cause mortality (Clinical Outcome #6)(At day 28 and day 90)
- Cohort B (Hospitalized) - Proportion negative swab. (Virologic/Immunological Outcome #2)(Days 0-7, 10, 12, 14, 18, 21, 25 and 28)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #6)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #14)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Ordinal scale (Clinical Outcome #1)(At Days 7, 21 and 28)
- Cohort A (Ambulatory) - Time RNA negativity (Virologic/Immunological Outcome #2)(Day 0 to Day 14)
- Cohort A (Ambulatory) - Proportion viremic (Virologic/Immunological Outcome #3)(Day 0 and Day 7)
- Cohort B (Hospitalized) - Readmission to hospital (Clinical Outcome #7)(From Day 0 -28 and from Day 0 - 90)
- Cohort B (Hospitalized) - Adverse (AEs) and Serious Adverse Events (SAEs) (Clinical Outcome #9)(Day 0 to day 28)
- Cohort B (Hospitalized) - Correlation with interferon lambda 4 (IFNL4) genotype (Virologic/Immunological Outcome #4)(Through Day 14)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #7)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #10)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Dose reduction or dose omission (Clinical Outcome #10)(Day 5 to day 9)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #11)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #13)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Quantitative viral load by nasal swab (Virologic/Immunological Outcome #3)(Day 0 - Day 28)
- Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #17)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #18)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Proportion with Antibody (Virologic/Immunological) Outcome #20)(At Day 7, 14, 21, and 28)
- Cohort B (Hospitalized) - Time to viral negativity (Virologic/Immunological Outcome #1)(Day 0 - Day 28)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #5)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #8)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #9)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #12)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #19)(From Day 0 - Day 7 and to Day 14, 21, and 28)
- Cohort B (Hospitalized) - Proportion with viremia (Virologic/Immunological Outcome #21)(Day 0, Day 7, 14, 21, and 28)