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Clinical Trial
. 2023 Nov 30;77(11):1521-1530.
doi: 10.1093/cid/ciad409.

Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial

Yanfen Guan  1 , Amy Puenpatom  1 , Matthew G Johnson  1 , Ying Zhang  1 , Yujie Zhao  1 , Joseph Surber  2 , Aaron Weinberg  3 , Carlos Brotons  4 , Roman Kozlov  5 , Rudy Lopez  6 , Kathleen Coetzee  7 , Joel Santiaguel  8 , Jiejun Du  1 , Angela Williams-Diaz  1 , Michelle Brown  1 , Amanda Paschke  1 , Carisa De Anda  1 , Josephine M Norquist  1
Affiliations
Clinical Trial

Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial

Yanfen Guan et al. Clin Infect Dis. .

Abstract

Background: Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19.

Methods: Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no." Time to sustained symptom resolution/improvement was defined as the number of days from randomization to the first of 3 consecutive days of reduced severity, without subsequent relapse. Time to symptom progression was defined as the number of days from randomization to the first of 2 consecutive days of worsening severity. The Kaplan-Meier method was used to estimate event rates at various time points. The Cox proportional hazards model was used to estimate the hazard ratio between molnupiravir and placebo.

Results: For most targeted COVID-19 symptoms, sustained resolution/improvement was more likely, and progression was less likely, in the molnupiravir versus placebo group through day 29. When evaluating 5 distinctive symptoms of COVID-19, molnupiravir participants had a shorter median time to first resolution (18 vs 20 d) and first alleviation (13 vs 15 d) of symptoms compared with placebo.

Conclusions: Molnupiravir treatment in at-risk, unvaccinated patients resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared with placebo. Clinical Trials Registration. ClinicalTrials.gov: NCT04575597.

Keywords: SARS-CoV-2; antiviral; clinical trial; public health; β-D-N4-hydroxycytidine.

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Conflict of interest statement

Potential conflicts of interest. Y. G., A. P., M. G. J., Y. Z., Y. Z., A. W.-D., M. B., A. P., C. D. A., and J. M. N. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and may own and/or hold stock options in Merck & Co, Inc, Rahway, NJ, USA. J. D. was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, at the time of study conduct and holds stock and/or stock options in Merck & Co, Inc, Rahway, NJ, USA. A. Puenpatom also reports travel support from Merck & Co., Inc., Rahway, NJ, USA. A. W. holds stock and/or stock options in Carbon Health Technologies, Inc, and CurieAI for advisory work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Sustained resolution/improvement of COVID-19 symptoms through day 29 (MITT population). Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019; MITT, modified intention-to-treat. *Number of participants eligible for sustained resolution/improvement (ie, those who had the corresponding symptom at baseline) in the MITT population. †From the product-limit (Kaplan-Meier) method for censored data. ‡Based on stratified Cox regression model with Efron's method of tie handling with treatment as covariates and randomization stratum as the stratification factor. A hazard ratio >1 favors the molnupiravir group.
Figure 2.
Figure 2.
Progression of COVID-19 symptoms through day 29 (MITT population). Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019; MITT, modified intention-to-treat. *Number of participants eligible for sustained resolution/improvement (ie, those who had the corresponding symptom at baseline) in the MITT population. †From the product-limit (Kaplan-Meier) method for censored data. ‡Based on stratified Cox regression model with Efron's method of tie handling with treatment as covariates and randomization stratum as the stratification factor. A hazard ratio <1 favors the molnupiravir group.
Figure 3.
Figure 3.
Proportion of participants with (A) sustained resolution/improvement or (B) progression of distinctive COVID-19 symptoms at day 3, day 5 (EOT), and day 10 (MITT population). Distinctive symptoms = five symptoms commonly associated with COVID-19 at the time of trial conduct. In panel A, a higher percentage indicates more favorable outcomes (sustained resolution/improvement), while in panel B, a higher percentage indicates less favorable outcomes (progression of symptoms). Abbreviations: COVID-19, coronavirus disease 2019; EOT, end of treatment; MITT, modified intention-to-treat.
Figure 4.
Figure 4.
Proportion of participants with moderate to severe rating for distinctive COVID-19 symptoms through day 29 (MITT population). Participants with available data at each time point are shown. Distinctive symptoms = five symptoms commonly associated with COVID-19 at the time of trial conduct. For “loss of smell” and “loss of taste,” the figure demonstrates proportion of participants who reported “yes” at each time point. Abbreviations: COVID-19, coronavirus disease 2019; MITT, modified intention-to-treat.
Figure 5.
Figure 5.
Median time to first resolution and time to first alleviation of distinctive COVID-19 symptoms through day 29 (MITT population). Median time calculated as the average for the 5 symptoms from the product-limit (Kaplan-Meier) method for censored data. Distinctive symptoms = five symptoms commonly associated with COVID-19 at the time of trial conduct (ie, shortness of breath or difficulty breathing, cough, fatigue, loss of smell, and loss of taste). Error bars represent the 95% confidence interval. One-sided P values based on log-rank test stratified by randomization stratification stratum. An HR >1 favors the molnupiravir group. Based on stratified Cox regression model with Efron's method of tie handling with treatment as covariates and randomization stratum as the stratification factor. Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019; HR, hazard ratio; MITT, modified intention-to-treat.
Figure 6.
Figure 6.
Median time to alleviation and time to sustained alleviation of all 15 targeted signs and symptoms through day 29 (MITT population). Median time calculated as the average of all 15 targeted symptoms from the product-limit (Kaplan-Meier) method for censored data. Error bars represent the 95% confidence interval. One-sided P values based on log-rank test stratified by randomization stratification stratum. An HR >1 favors the molnupiravir group. Based on stratified Cox regression model with Efron's method of tie handling with treatment as covariates and randomization stratum as the stratification factor. Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019; HR, hazard ratio; MITT, modified intention-to-treat.
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