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 humantrials in viral hepatitis, confirming it safety and tolerability. It is particularlyattractive for consideration in the use of acute respiratory illness due to the highexpression of the lambda receptor in lung epithelia. We propose to evaluatepeginterferon-lambda in ambulatory patients with mild to moderate COVID-19.
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.
Drug: Peginterferon Lambda-1A
Peginterferon lambda is a covalent conjugate of human recombinant non-pegylated IFN
lambda (IFN L) and a 20-kDa linear PEG chain.
Peginterferon lambda Injection is a sterile, nonpyrogenic, ready-to-use solution (0.4
mg/mL) that is clear to opalescent, colorless to pale yellow, and essentially free of
particles. Lambda Injection is provided in a 1-mL long Type I glass syringe (0.18
mg/syringe) with a staked 29-gauge, 1/2- inch, thin-walled needle. The syringe has a
rigid needle shield and is stoppered with a plunger stopper. Syringes are prefilled with
a solution of Peginterferon lambda Injection, mannitol, L-histidine, polysorbate 80,
hydrochloric acid, and water for injection; they are intended for a single use at
adjustable doses. The syringe is marked with dose indicator lines, which are used as a
reference point for administering the correct dose.
Other: Placebo
The placebo will be 0.9% sodium chloride (normal saline) solution. 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.
Inclusion Criteria:
1. Adult 18 years of age or older.
2. Symptomatic and within 7 days of symptom onset.
3. High risk for severe disease (as defined by one or more of the following):
1. Age >50
2. Diabetes mellitus requiring therapy
3. Hypertension on medication
4. BMI >30 kg/m2
5. Cardiovascular disease
6. Asthma requiring chronic controller medication
7. Symptomatic respiratory disease
8. Immunosuppressed patients (to maximum of 10mg prednisone daily +/- other
immunosuppressive agents)
9. Documented fever (>38C)
10. 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)
4. Discharged to home isolation.
5. Willing and able to provide informed consent (including by substitute decision
maker).
6. Willing and able to follow-up by phone or videoconference.
7. 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.
Exclusion Criteria:
1. Pregnancy (or positive urine pregnancy test) or lactating.
2. More than 14 days following completion of SARS-CoV-2 vaccition series
3. The following pre-existing medical conditions:
1. Known cirrhosis with any history of decompensation (ascites, variceal bleeding
or hepatic encephalopathy)
2. Known chronic kidney disease with estimated creatinine clearance < 30 mL/minute
or need for dialysis
3. Uncontrolled severe psychiatric disorder - schizophrenia, bipolar disorder,
depression with prior suicidality
4. Uncontrolled seizures or seizure in the prior 1 month
5. 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
4. Known alcohol or drug dependence that in the opinion of the investigator would
impair study participation.
5. Known prior intolerance to interferon treatment.
6. Enrolment in another clinical trial testing an antiviral agent or receipt of an
antiviral agent for COVID-19 in the past 7 days.
7. Use of investigational, off-label therapy for COVID-19, or unproven therapy for
COVID-19.
Toronto General Hospital
Toronto, Ontario, Canada
Jordan Feld, MD, Principal Investigator
University Health Network, Toronto