Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While most cases are mild or do not show any clinical signs or symptoms, progressive disease can result in hospitalization, requirement for assisted breathing (mechanical ventilation), and substantial morbidity and death (Johns Hopkins University).

Some treatment options for patients with severe disease requiring hospitalization have become available. Remdesivir and corticosteroids have emerged as the treatment of choice for critically ill patients. Still, interventions that can be administered early during the course of infection to prevent disease progression and longer-term complications are urgently needed (Kim 2020). Multiple antiviral monoclonal antibodies (mAbs) are under development, specifically targeting SARS-CoV-2’s spike protein and thereby its ability to enter the host cell for viral replication. Recent data indicate this therapeutic mode of action is beneficial in ambulatory patients treated within the first 7 days after symptom onset, reducing the need for subsequent clinician consultations (hospitalizations, emergency room visits, urgent case or another physician contact for COVID-19) by half (Chen 2020, Weinreich 2020, Gottlieb 2021.

The rationale for the clinical development of ensovibep (MP0420) is to provide a safe and effective therapy for SARS-CoV-2 infections. Effective in that it prevents or reduces the need for hospitalization and safe in that it does not provoke excessive immunological and inflammatory responses in patients with pre-existing SARS-CoV-2 infection.

This study is a two part, randomized, double-blind, multicentre, Phase 2 and Phase 3 study designed to assess the efficacy, safety, tolerability, and PK of ensovibep. Part A is the Phase 2 component of the study that will serve to show proof of efficacy and to support selection of the best efficacious and safe dose; Part B is the Phase 3 component of the study that will confirm efficacy and safety of ensovibep at the dose selected based on the data from Part A. The study will recruit ambulatory symptomatic adult patients diagnosed with COVID-19 with onset of symptoms within 7 days prior to dosing and with a positive rapid antigen test on the day of dosing

The primary objectives are for Part A, to demonstrate superiority of ensovibep, compared to placebo, in reducing SARS-CoV-2 viral load through Day 8. Part B is to demonstrate superiority of ensovibep, compared to placebo, in reducing the occurrence of hospitalizations (≥ 24 hours of acute care) and/or emergency room visits related to COVID-19 or death from any cause up to Day 29. At our site, we plan to enrol about 400 patients.

Data analysis in Part A will involve Time-weighted change from baseline (Day 1) to Day 8 in log10 SARS-CoV-2 viral load in nasopharyngeal swabs calculation for each patient. In Part B, the cumulative proportion of participants experiencing hospitalizations (≥ 24 hours of acute care) and/or emergency room visits related to COVID-19 or death from any cause up to day 29 will be estimated for each randomized group using Kaplan-Meier methods to take account of losses to follow-up. The difference between randomized groups in the estimated log cumulative proportion will be calculated and the variance for this difference will be obtained using Greenwood’s formula. Two-sided 95% confidence intervals (adjusted for an interim analysis) and associated p-value for the test of no difference between groups will then be obtained.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While most cases are mild or asymptomatic, progressive disease can result in hospitalization, requirement for mechanical ventilation, and substantial morbidity and mortality (Johns Hopkins University).

Some treatment options for patients with severe disease requiring hospitalization have become available. Remdesivir and corticosteroids have emerged as the treatment of choice for critically ill patients. Still, interventions that can be administered early during the course of infection to prevent disease progression and longer-term complications are urgently needed (Kim 2020). Multiple antiviral monoclonal antibodies (mAbs) are under development, specifically targeting SARS-CoV-2’s spike protein and thereby its ability to enter the host cell for viral replication. Recent data indicate this therapeutic mode of action is beneficial in ambulatory patients treated within the first 7 days after symptom onset, reducing the need for subsequent “medically attended visits” (hospitalizations, emergency room visits, urgent case or another physician contact for COVID-19) by half (Chen 2020, Weinreich 2020, Gottlieb 2021.

This study is a two part, randomized, double-blind, multicentre, Phase 2 and Phase 3 study designed to assess the efficacy, safety, tolerability, and PK of ensovibep. Part A is the Phase 2 component of the study that will serve to show proof of efficacy and to support selection of the best efficacious and safe dose; Part B is the Phase 3 component of the study that will confirm efficacy and safety of ensovibep at the dose selected based on the data from Part A. The study will recruit ambulatory symptomatic adult patients diagnosed with COVID-19 with onset of symptoms within 7 days prior to dosing and with a positive rapid antigen test on the day of dosing.

The primary objectives are for Part A, to demonstrate superiority of ensovibep, compared to placebo, in reducing SARS-CoV-2 viral load through Day 8. Part B is to demonstrate superiority of ensovibep, compared to placebo, in reducing the occurrence of hospitalizations (≥ 24 hours of acute care) and/or emergency room visits related to COVID-19 or death from any cause up to Day 29. At our site we plan to enrol about 400 patients

Data analysis in Part A will involve Time-weighted change from baseline (Day 1) to Day 8 in log10 SARS-CoV-2 viral load in nasopharyngeal swabs calculation for each patient. In Part B, the cumulative proportion of participants experiencing hospitalizations (≥ 24 hours of acute care) and/or emergency room visits related to COVID-19 or death from any cause up to day 29 will be estimated for each randomized group using Kaplan-Meier methods to take account of losses to follow-up. The difference between randomized groups in the estimated log cumulative proportion will be calculated and the variance for this difference will be obtained using Greenwood’s formula. Two-sided 95% confidence intervals (adjusted for an interim analysis) and associated p-value for the test of no difference between groups will then be obtained.