Interferon Lambda for Immediate Antiviral Therapy at Diagnosis in COVID-19
- Registration Number
- NCT04354259
- Lead Sponsor
- University Health Network, Toronto
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 157
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ambulatory Cohort - placebo 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. Hospitalized Cohort - placebo 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. Ambulatory Cohort - Treatment Peginterferon Lambda-1A to receive a single dose of peginterferon lambda 180µg SC at baseline (day 0). Hospitalized Cohort - Treatment Peginterferon Lambda-1A To receive a dose of peginterferon lambda 180µg SC at baseline and a second dose on day 5.
- Primary Outcome Measures
Name Time Method Cohort A (Ambulatory) - Treatment-emergent and treatment related serious adverse events (Primary Safety Endpoint) 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) At day 7 The proportion of participants with negative SARS-CoV-2 RNA on nasopharyngeal swab.
Cohort B (Hospitalized) - Ordinal Scale (Primary Efficacy Endpoint) 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) Day 0 to Day 28 The rate of treatment-emergent and treatment-related serious adverse events (SAEs)
- Secondary Outcome Measures
Name Time Method Cohort B (Hospitalized) - COVID-19-related mortality (Clinical Outcome #8) At day 28 COVID-19-related mortality
Cohort A (Ambulatory) - Symptom severity scores (Clinical Outcome #2) Day 0 to Day 7 Change in relative categorical symptom scores (respiratory, gastrointestinal, fever) - none, mild, moderate, severe and no change, worse, better
Cohort A (Ambulatory) - Adverse and serious adverse events (Clinical Outcome #4) Day 0 to Day 14 Adverse events and serious adverse events
Cohort A (Ambulatory) - Symptoms in household contacts (Transmission Outcome #1) Day 0 to Day 14 Proportion with symptom development in household contacts (categorical symptom type yes/no)
Cohort B (Hospitalized) - ICU admission (Clinical Outcome #2) Day 0 to day 28 Proportion with ICU admission during hospitalization
Cohort B (Hospitalized) - Change in respiratory symptom score (Clinical Outcome #5) Day 0 to 7, Day 0 to 14, and Day 0 to 28 Change in respiratory symptom score (score 0 to 7 with higher scores indicating more severe disease)
Cohort A (Ambulatory) - Hospitalization (Clinical Outcome #3) Day 0 to Day 14 Proportion with need for hospital admission
Cohort A (Ambulatory) - Symptom Resolution (Clinical Outcome #1) Day 0 to Day 14 Time to resolution of symptoms (fever, cough, diarrhea)
Cohort A (Ambulatory) - Swab negative at day 3 (Virologic/Immunological Outcome #1) At Day 3 Proportion negative for SARS-CoV-2 RNA by nasopharyngeal swab
Cohort A (Ambulatory) - Correlation with interferon lambda 4 genotype (Virologic/Immunological Outcome #5) Through day 7 Correlation of virologic response with interferon lambda 4 (IFNL4) genotype
Cohort A (Ambulatory) - COVID-19 in household contacts (Transmission Outcome #2) At Day 30 Proportion with confirmed diagnosis of COVID-19 in household contacts
Cohort B (Hospitalized) - Need for intubation (Clinical Outcome #3) Day 0 to Day 14 and to Day 28 Proportion with need for intubation
Cohort B (Hospitalized) - Length of hospital stay (Clinical Outcome #4) Day 0 to Day 14 Length of hospital stay (days)
Cohort A (Ambulatory) - Proportion with antibodies (Virologic/Immunological Outcome #4) Day 0 and Day 7 Proportion with SARS-CoV-2 antibodies blood
Cohort B (Hospitalized) - All-cause mortality (Clinical Outcome #6) At day 28 and day 90 All-cause mortality
Cohort B (Hospitalized) - Proportion negative swab. (Virologic/Immunological Outcome #2) Days 0-7, 10, 12, 14, 18, 21, 25 and 28 Proportion negative for SARS-CoV-2 RNA by mid-turbinate swab
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #6) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in white blood cell count over time.
Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #14) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in ferritin over time.
Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #15) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in lactate dehydrogenase over time.
Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #16) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in c-reactive protein over time
Cohort A (Ambulatory) - Time RNA negativity (Virologic/Immunological Outcome #2) Day 0 to Day 14 Time to SARS-CoV-2 RNA negativity on mid-turbinate nasal swab or saliva
Cohort A (Ambulatory) - Proportion viremic (Virologic/Immunological Outcome #3) Day 0 and Day 7 Proportion with SARS-CoV-2 RNA in blood.
Cohort B (Hospitalized) - Ordinal scale (Clinical Outcome #1) At Days 7, 21 and 28 Clinical status on the ordinal scale
Cohort B (Hospitalized) - Readmission to hospital (Clinical Outcome #7) From Day 0 -28 and from Day 0 - 90 Proportion with readmission to hospital
Cohort B (Hospitalized) - Adverse (AEs) and Serious Adverse Events (SAEs) (Clinical Outcome #9) Day 0 to day 28 Adverse (AEs) and Serious Adverse Events (SAEs)
Cohort B (Hospitalized) - Correlation with interferon lambda 4 (IFNL4) genotype (Virologic/Immunological Outcome #4) Through Day 14 Correlation of virologic response with interferon lambda 4 (IFNL4) genotype
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #7) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in lymphocyte count over time.
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #10) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in AST over time.
Cohort B (Hospitalized) - Dose reduction or dose omission (Clinical Outcome #10) Day 5 to day 9 Frequency of dose reduction or dose omission for the second dose of peginterferon lambda
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #11) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in ALP over time.
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #13) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in albumin over time.
Cohort B (Hospitalized) - Quantitative viral load by nasal swab (Virologic/Immunological Outcome #3) Day 0 - Day 28 Change in quantitative SARS-CoV-2 RNA by mid-turbinate swab over time
Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #17) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in D-dimers over time.
Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #18) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in creatine kinase over time.
Cohort B (Hospitalized) - Proportion with Antibody (Virologic/Immunological) Outcome #20) At Day 7, 14, 21, and 28 Proportion with SARS-CoV-2 Antibody.
Cohort B (Hospitalized) - Time to viral negativity (Virologic/Immunological Outcome #1) Day 0 - Day 28 Time to SARS-CoV-2 RNA negativity.
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #5) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in hemoglobin over time.
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #8) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in platelet count over time.
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #9) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in ALT over time.
Cohort B (Hospitalized) - Safety Markers (Virologic/Immunological Outcome #12) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in bilirubin over time.
Cohort B (Hospitalized) - Inflammatory Markers (Virologic/Immunological Outcome #19) From Day 0 - Day 7 and to Day 14, 21, and 28 Change in troponin over time.
Cohort B (Hospitalized) - Proportion with viremia (Virologic/Immunological Outcome #21) Day 0, Day 7, 14, 21, and 28 Proportion with SARS-CoV-2 RNA in blood
Trial Locations
- Locations (7)
University of Calgary
🇨🇦Calgary, Alberta, Canada
Hospital das Clínicas da Faculdade de Medicina de Botucatu
🇧🇷Botucatu, Brazil
Hospital das Clínicas São Paulo
🇧🇷Sao Paulo, Brazil
Hospital Alemão Oswaldo Cruz
🇧🇷São Paulo, Brazil
University Health Network
🇨🇦Toronto, Ontario, Canada
Michael Garron Hospital
🇨🇦Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada