Speaker

Edward Mills, PhD, FRCP
Professor
Department of Health Research Methods, Evidence & Impact
McMaster University, Canada

Jeffrey S. Glenn, MD, PhD
Joseph D. Grant Professor and Professor of Microbiology and Immunology
Stanford University

 

Slides

 

Keywords

TOGETHER, COVID-19, Peginterferon Lambda

 

Key Points

• TOGETHER is a randomized adaptive platform trial that was initiated in June 2020 to investigate the efficacy of repurposed treatments for COVID-19 disease among high-risk adult outpatients. TOGETHER has been through 14 interventions within the trial and has four active arms.

• For the overall trial, anyone over the age of 18 with a known risk factor for disease progression is eligible; they have to present at an outpatient care setting with an acute clinical condition consistent with COVID-19 and have a positive rapid test in the clinic. The consent process is in-person, which was challenging in the beginning days of the trial.

• The arm evaluating Peginterferon Lambda is a multicenter, investigator sponsored, randomized placebo-controlled Phase 3 study in Brazil with 12 sites and Canada (5 sites). It is a single injection of peginterferon lambda verses placebo, patients were randomized within 7 days of symptom onset and positive SARS-CoV-2 test. The trial has enrolled 1,900 high-risk non-hospitalized and 84% of patients were vaccinated to some extent, from July 2021-Feb 2022. The primary endpoint is either reduction in COVID-19-related hospitalizations or emergency hospital visits through day 28 and hospitalization or death.

• The primary outcome had a relative risk reduction of 51% when given 7 days or less of symptoms before treatment; when the trial looked at early treated patients (less than 3 days of symptoms before treatment) the treatment effect when up to 57% risk reduction. 43% risk reduction for hospitalization (65% reduction when treated early). Hospitalization or death due to COVID-19 was 41% if treated within 7 days and 65% if treated within 3 days of symptoms. It was a big treatment effect observed in a predominantly vaccinated population.

• When compared to other drug trials for COVID-19, there was a 61% reduction for the primary outcome and 54% reduction in hospitalization and death for unvaccinated populations. In the same population, if treated early there was a 65% reduction for the primary outcome and hospitalization or death due to COVID-19. The unvaccinated and early treatment population saw a 89% risk reduction, which is very similar to what was identified in the Paxlovid trial.

Discussion Themes

-Were any concerns raised on ethics of keeping a placebo arm in this population? For the countries we are working in this has not been an issue because of the drugs that were available during the time of the study.

-Immunosuppressed patients might be a subgroup that would particularly benefit from this type of treatment.

Learn more about TOGETHER.

 

Tags

#pctGR, @Collaboratory1