TOGETHER-Toronto: A Phase III 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
- 3 期
- 入组人数
- 763
- 试验地点
- 1
- 主要终点
- COVID-19 related urgent care visit, emergency room assessment, hospitalization or death by Day 28 (Primary efficacy endpoint)
研究概览
简要总结
Interferon (IFN) lambda is one of the fundamental responses of the innate immune system. Peginterferon lambda is a long-acting form that has been studied extensively in human trials in viral hepatitis, confirming it safety and tolerability. It is particularly attractive for consideration in the use of acute respiratory illness due to the high expression of the lambda receptor in lung epithelia. We propose to evaluate peginterferon-lambda in ambulatory patients with mild to moderate COVID-19.
详细描述
In this study, individuals who attend an Assessment Centre/Emergency Department to be swabbed for COVID-19 and deemed well enough for home isolation will be informed about the study. There will be two major routes of recruitment. Where feasible, a rapid point-of-care (POC) laminar flow based COVID-19 test (the Abbott PanBio) will be performed and those who do not have a POC test at the assessment centre will be tested by PCR.
Interested participants who contact study staff will be confirmed to have a positive COVID-19 test. Once confirmed will be further screened for eligibility criteria by research study staff. After review, a consent form will be emailed to the participant and informed consent will be obtained through witnessed telephone consent from the participant or a substitute decision maker (SDM). Participants who consent will be randomized to receive a single subcutaneous injection of Peginterferon lambda 180µg or saline placebo.
Patients will be followed remotely with visits. In addition, participants will also attend outpatient clinic for swabs and blood work for routine laboratory and inflammatory markers on Days 7 and 14 with the primary endpoint being the time to SARS-CoV-2 RNA negativity and the proportion with COVID-19 related emergency room assessment >6 hours, hospitalization or death by Day 28. Numerous secondary endpoints will be evaluated as well.
Safety data will be reviewed by the Data Safety and Monitoring Committee after the first 50% of randomized participants complete 14 days of follow-up after 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
- •Adult 18 years of age or older.
- •Symptomatic and within 7 days of symptom onset.
- •High risk for severe disease (as defined by one or more of the following):
- •Diabetes mellitus requiring therapy
- •Hypertension on medication
- •BMI >30 kg/m2
- •Cardiovascular disease
- •Asthma requiring chronic controller medication
- •Symptomatic respiratory disease
- •Immunosuppressed patients (to maximum of 10mg prednisone daily +/- other immunosuppressive agents)
- •Documented fever (>38C)
- •One or more of the following symptoms: cough, shortness of breath (SOB), pleuritic chest pain and/or myalgias (to a maximum of 25% of enrollment)
- •Discharged to home isolation.
- •Willing and able to provide informed consent (including by substitute decision maker).
- •Willing and able to follow-up by phone or videoconference.
- •Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication. Female patients of childbearing potential are all those except patients who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal.
排除标准
- •Pregnancy (or positive urine pregnancy test) or lactating.
- •More than 14 days following completion of SARS-CoV-2 vaccition series
- •The following pre-existing medical conditions:
- •Known cirrhosis with any history of decompensation (ascites, variceal bleeding or hepatic encephalopathy)
- •Known chronic kidney disease with estimated creatinine clearance < 30 mL/minute or need for dialysis
- •Uncontrolled severe psychiatric disorder - schizophrenia, bipolar disorder, depression with prior suicidality
- •Uncontrolled seizures or seizure in the prior 1 month
- •Any other underlying medical (cardiac, liver, renal, neurological, respiratory) or psychiatric condition that in the view of the investigator would preclude use of peginterferon lambda
- •Known alcohol or drug dependence that in the opinion of the investigator would impair study participation.
- •Known prior intolerance to interferon treatment.
- •Enrolment in another clinical trial testing an antiviral agent or receipt of an antiviral agent for COVID-19 in the past 7 days.
- •Use of investigational, off-label therapy for COVID-19, or unproven therapy for COVID-19.
研究组 & 干预措施
Treatment
To receive a dose of peginterferon lambda 180mcg SC at baseline (Day 0).
干预措施: Peginterferon Lambda-1A (Drug)
Placebo
Patients in this arm will receive a single SC dose 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)
结局指标
主要结局
COVID-19 related urgent care visit, emergency room assessment, hospitalization or death by Day 28 (Primary efficacy endpoint)
时间窗: At day 28
Proportion with COVID-19-related emergency room assessment, hospitalization, or death by Day 28
SARS-CoV-2 RNA negativity (Primary virological endpoint)
时间窗: Day 0 to Day 28
The time to SARS-CoV-2 RNA negativity.
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) by Day 28.
次要结局
- Time to viral negativity (Virologic/immunological outcome #1)(Day 0 to Day 14)
- All symptom resolution (Clinical outcome #4)(Day 0 to Day 28)
- Respiratory symptom resolution (Clinical Outcome #1)(Day 0 to Day 28)
- Oxygen saturation on room air (Clinical outcome #5)(Day 0 to Day 14)
- Hospitalization (Clinical outcome #2)(Day 0 to Day 28)
- Negative for SARS-CoV-2 RNA (Virologic/immunological outcome #5)(Day 7)
- Negative for SARS-CoV-2 RNA (Virologic/immunological outcome #6)(Day 14)
- Death (Clinical outcome #3)(Day 0 to Day 28)
- Seeking care from healthcare professional for COVID-19 (Clinical outcome #6)(Day 0 - Day 14)
- Hospital Admission (Clinical outcome #7)(Day 0 to Day 28)
- Mean log of SARS-CoV-2 RNA (Virologic/immunological outcome #2)(Day 3, 5, 7, 10 and 14)
- Mean log decline in SARS-CoV-2 RNA (Virologic/immunological outcome #3)(Day 3, 5, 7, 10 and 14)
- Negative for SARS-CoV-2 RNA (Virologic/immunological outcome #4)(Day 3)
- Proportion with antibodies (Virologic/immunological outcome #7)(Day 0, 7, 14 and 90)
- Correlation with interferon lambda 4 genotype (Virologic/immunological outcome #8)(Day 0 to Day 28)
- Laboratory markers (Virologic/immunological outcome #9)(Day 0 to Day 7 and Day 7 to Day 14.)
- Laboratory markers (Virologic/immunological outcome #10)(Day 0 to Day 7 and Day 7 to Day 14.)
- Laboratory markers (Virologic/immunological outcome #11)(Day 0 to Day 7 and Day 7 to Day 14.)
- Laboratory markers (Virologic/immunological outcome #12)(Day 0 to Day 7 and Day 7 to Day 14.)
- Laboratory markers (Virologic/immunological outcome #13)(Day 0 to Day 7 and Day 7 to Day 14.)
- Laboratory markers (Virologic/immunological outcome #14)(Day 0 to Day 7 and Day 7 to Day 14.)
- Laboratory markers (Virologic/immunological outcome #15)(Day 0 to Day 7 and Day 7 to Day 14.)
- Inflammatory markers (Virologic/immunological outcome #16)(Day 0 to Day 7 and Day 7 to Day 14.)
- COVID-19 in household contacts (Transmission outcome #1)(Day 0 to Day 28)
- Inflammatory markers (Virologic/immunological outcome #17)(Day 0 to Day 7 and Day 7 to Day 14.)
- Inflammatory markers (Virologic/immunological outcome #18)(Day 0 to Day 7 and Day 7 to Day 14.)
- Inflammatory markers (Virologic/immunological outcome #19)(Day 0 to Day 7 and Day 7 to Day 14.)