Covid-19 living Data

Peginterferon Lambda-1 vs Placebo (RCT)

Mild outpatients

FOREST PLOTS -2022-10-07

Studies description

Trial NCT04354259
Publication ILIAD - 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
Participants
	Randomized participants : Peginterferon Lambda-1=30 Placebo=30
	Characteristics of participants N= 60 Mean age : NR 25 males Severity : Mild: n= 49/ Asymptomatic: n=11
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 avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication:
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.

Trial NCT04331899
Publication Jagannathan P, Nature (2021) (published paper)
Dates: 2020-04-25 to 2020-07-17
Funding: Mixed (Anonymous donors to Stanford University; Eiger BioPharmaceuticals (drug))
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Single center / USA Follow-up duration (days): 28
Inclusion criteria	Adults aged 18-65 years with an FDA emergency use authorized reverse transcription-polymerase chain reaction (RT-PCR) positive for SARS-CoV-2 within 72 hours from swab to the time of enrolment were eligible for participation in this study both symptomatic and asymptomatic patients were included given reports finding that both CT values and presence of infectious virus were similar in samples from asymptomatic and symptomatic persons symptomatic individuals were eligible given the presence of mild to moderate symptoms without signs of respiratory distress asymptomatic individuals were eligible if infection was initial diagnosis of SARS-CoV-2 infection
Exclusion criteria	Current or imminent hospitalization respiratory rate >20 breaths per minute room air oxygen saturation <94% pregnancy or breastfeeding history of decompensated liver disease recent use of interferons, antibiotics, anticoagulants or other investigational and/or immunomodulatory agents for treatment of COVID-19 prespecified lab abnormalities
Interventions
	Treatment Peginterferon Lambda-1 180 mcg subcutaneous injection once off
	Control Placebo
Participants
	Randomized participants : Peginterferon Lambda-1=60 Placebo=60
	Characteristics of participants N= 120 Mean age : NR 70 males Severity : Mild: n= 112/ Asymptomatic: n=8
Primary outcome
	In the register Duration of Viral shedding of SARS-CoV-2 by qRT-PCR [ Time Frame: 28 days ] Time to first of two consecutive negative respiratory secretions obtained by oropharyngeal and/or anterior nare swabs for SARS-CoV-2 by qRT-PCR
	In the report Time to first of two consecutive negative oropharyngeal tests for SARS-CoV-2 by RT-PCR
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: 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 the preprint article, the protocol, SAP, the study registry and supplementary appendix were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The primary outcome indicated in the trial registry reflects the primary outcome reported in the paper. All secondary outcomes were added to the trial registration after completion of study recruitment and follow up, and the design was changed from open-label to single-blind. Quote: "The protocol was amended on June 16th, 2020 after 54 participants were enrolled but before results were available to include adults up to 75 years of age and eliminate exclusion criteria for low white blood cell and lymphocyte count." On 12th of April, 2021, this study was updated based on the published report. This study was updated on September 28th, 2022 with data extracted from the registry.