Assessment of symptoms in COMET-ICE, a phase 2/3 study of sotrovimab for early treatment of non-hospitalized patients with COVID-19.

BACKGROUND: The COMET-ICE trial demonstrated that sotrovimab clinically and statistically significantly reduces the risk of all-cause > 24-h hospitalization or death due to any cause among patients with COVID-19 at high risk of disease progression. Patient-reported outcomes are important to capture symptom burden of COVID-19 and assess treatment effectiveness. This study investigated symptoms and their impact over the acute phase of COVID-19 infection among patients on sotrovimab versus placebo. METHODS: Randomized (1:1), double-blind, multicenter, placebo-controlled, phase 2/3 study in 57 centers across five countries. Participants were non-hospitalized patients with symptomatic, mild-to-moderate COVID-19 and ≥ 1 baseline risk factor for disease progression (aged ≥ 55 years or ≥ 1 of the following: diabetes requiring medication, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate-to-severe asthma). An intravenous infusion of sotrovimab 500 mg or placebo was administered on Day 1. The FLU-PRO Plus questionnaire was administered once-daily with 24-h recall from Day 1-21, and at Day 29. Intensity and duration of COVID-19 symptoms were determined from area under the curve (AUC) and mean change in total and individual domain scores through Days 7, 14, and 21. Time to symptom alleviation was assessed. RESULTS: In total, 1057 patients were randomized to sotrovimab (n = 528) or placebo (n = 529). At Day 7, mean decrease in FLU-PRO Plus total score (measured by AUC) was statistically significantly greater for patients on sotrovimab (-3.05 [95% confidence interval (CI) -3.27 to -2.83]) than placebo (-1.98 [95% CI -2.20 to -1.76]; difference -1.07 [95% CI -1.38 to -0.76]; p < 0.001). Significant differences were also observed at Days 14 and 21. A more rapid decline in symptom severity was observed with sotrovimab versus placebo through Week 1 and the first 21 days post-treatment. By Day 21, 41% of patients on sotrovimab and 34% on placebo reported symptom resolution. In a post-hoc analysis, median time to symptom alleviation was 4 and 6 days, respectively. CONCLUSIONS: Sotrovimab provides significant and rapid improvements in patient-reported COVID-19 symptoms, as measured by the FLU-PRO Plus. These results further show the benefits of sotrovimab in alleviating symptoms among high-risk patients with COVID-19. Trial registration ClinicalTrials.Gov: NCT04545060 ( https://clinicaltrials.gov/ct2/show/NCT04545060 ). Date of registration: September 10, 2020 (retrospectively registered).

Content validity and psychometric properties of the inFLUenza Patient-Reported Outcome Plus (FLU-PRO Plus©) instrument in patients with COVID-19.

PURPOSE: A well-defined and reliable patient-reported outcome instrument for COVID-19 is important for assessing symptom severity and supporting research studies. The InFLUenza Patient-Reported Outcome (FLU-PRO) instrument has been expanded to include loss of taste and smell in the FLU-PRO Plus, to comprehensively cover COVID-19 symptoms. Our studies were designed to evaluate and validate the FLU-PRO Plus among patients with COVID-19. METHODS: Two studies were conducted: (1) a qualitative, non-interventional, cross-sectional study of patients with COVID-19 involving hybrid concept elicitation and cognitive debriefing interviews; (2) a psychometric evaluation of the measurement properties of FLU-PRO Plus, using data from COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial-Intent to Care Early). RESULTS: In the qualitative interviews (n = 30), all 34 items of the FLU-PRO Plus were considered relevant to COVID-19, and participants determined the questionnaire was easily understood, well written, and comprehensive. In the psychometric evaluation (n = 845), the internal consistency reliability of FLU-PRO Plus total score was 0.94, ranging from 0.71 to 0.90 for domain scores. Reproducibility (Day 20-21) was 0.83 for total score, with domain scores of 0.67-0.89. Confirmatory factor analysis with the novel smell/taste domain demonstrated an acceptable fit to the data. CONCLUSION: The content, reliability, validity, and responsiveness of the FLU-PRO Plus in the COVID-19 population were supported. Our results suggest that FLU-PRO Plus is a content- and psychometrically-valid, fit-for-purpose measure which is easily understood by patients. FLU-PRO Plus is a suitable PRO measure for evaluating symptoms of COVID-19 and treatment benefit directly from the patient perspective. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04545060, September 10, 2020; retrospectively registered.