Trial NCT04354259
Publication Feld JJ, Lancet Respir Med, 2021 (published paper)
Dates: 2020-05-18 to 2020-09-04
Funding: Mixed (Toronto COVID-19 Action Initiative; University of Toronto; Ontario First COVID-19 Rapid Research Fund; Eiger BioPharma (drug provision))
Conflict of interest: Yes
| Methods | |
| RCT Blinding: | |
| Location :
Multicenter / Canada Follow-up duration (days): 14 | |
| Inclusion criteria | Report: Individuals with SARS-CoV-2-infection confirmed by nasopharyngeal swab were eligible if they were within 7 days of symptom onset or first positive test if asymptomatic
Registry: Adult patients between the ages of 18 and 70 years; Discharged to home isolation; Willing and able to sign informed consent; Willing and able to follow-up by daily 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. |
| Exclusion criteria | Report: pregnancy or lactating; pre-existing immunosuppressive or other medical conditions that could be worsened by peginterferon-lambda
Registry: Requirement for hospital admission; Current immunosuppression due to medication (steroids, biologics, chemotherapy) or underlying condition such as known HIV or organ/bone marrow transplant; Known seizure disorder; Known retinal disease requiring therapy; Known autoimmune condition requiring therapy more intensive than intermittent non-steroidal anti-inflammatories in the prior 6 months (rheumatoid arthritis, lupus, inflammatory bowel disease); Known history of chronic obstructive pulmonary disease (COPD) or asthma associated with functional impairment or with any history of hospitalization for an exacerbation; Known cirrhosis with any history of decompensation (ascites, variceal bleeding or hepatic encephalopathy); Known chronic kidney disease with estimated creatine clearance < 50 mL/minute or need for dialysis; Severe psychiatric disorder - schizophrenia, bipolar disorder, depression with prior suicidality; 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; Advanced cancer or other illness with life expectancy of < 1 year; Known prior intolerance to interferon treatment; Enrolment in another clinical trial with use of any investigational agent in the prior 30 days; Use of off-label therapy for COVID-19. |
| Interventions | |
| Treatment
Peginterferon Lambda-1 180 mcg subcutaneous injection once off. |
|
| Control
Placebo Duration : 1 day | |
| Participants | |
| Randomized 60 participants (n1=30 / n2= 30) | |
| Characteristics of participants N=60 Mean age : NR 25 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=0 Critical: n=0 | |
| Primary outcome | |
| In the register Proportion swab negative at day 7 (Primary efficacy endpoint) (proportion of participants with negative SARS-CoV-2 RNA on nasopharyngeal swab); Treatment-emergent and treatment related serious adverse events (Primary Safety Endpoint) [Time Frame | |
| In the report Proportion of individuals with a negative MT swab for SARS-CoV-2 at Day 7; Incidence of treatment-emergent severe adverse events (SAEs) by Day 14 | |
| Documents available |
Protocol NR Statistical plan NR Data-sharing stated Yes |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment |
In addition to all available versions of the published manuscript/pre-print article, the trial registry and supplementary materials were used in data extraction and assessment of risk of bias. The study protocol and statistical analysis plan were not available but were referenced in the article. There were some differences between the registry and pre-print in population. The registry required RT-PCR confirmed COVID-19 within 5 days of symptom onset whereas in the pre-print article asymptomatic patients with positive PCR within 7 days of recruitment were included. Negative conversion between a positive PCR within 7 days of recruitment likely accounts for 25% of patients having negative PCR results at baseline. The proportions of PCR-negative patients at baseline are not balanced between groups (17% intervention, 33% placebo). The report presents viral negative conversion results for those with confirmed PCR as a subgroup analysis (i.e., without randomisation). Some secondary outcomes in the registry were not reported. There were no other substantive differences in study procedures and interventions between the pre-print article and the registry. This study was updated on March 19th using data from the published manuscript. |