The purpose of this study is to determine if a CGRP receptor antagonist may potentially blunt
the severe inflammatory response at the alveolar level, delaying or reversing the path
towards oxygen desaturation, ARDS, requirement for supplemental oxygenation, artificial
ventilation or death in patients with COVID-19 on supplemental oxygen.
* BHV-3500, formerly "vazegepant", is now referred to as "zavegepant" (za ve' je pant). The
World Health Organization (WHO) International Nonproprietary Names (INN) Expert Committee
revised the name to "zavegepant" which was accepted by the United States Adopted Names (USAN
) Council for use in the U.S. and is pending formal adoption by the INN for international
use.
Primary Outcomes
Description: a. Efficacy will be measured by the difference between groups in the meah 6-point severity rating at Day 15. The severity ratings are:
Death
Hospitalized, on invasive mechanical ventilation or ECMO
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, requiring supplemental oxygen
Hospitalized, not requiring supplemental oxygen
Not hospitalized
Measure: To compare the efficacy of zavegepant (BHV-3500) to placebo in subjects hospitalized with COVID-19 infection requiring supplemental oxygen, using a six-point rating scale at Day 15. .
Time: Baseline to Day 15
Secondary Outcomes
Measure: Proportion of subjects who have a 6-point severity rating of 5 or 6, are alive, and do not use supplemental oxygen as a procedure at Day 29. Time: Baseline to Day 29
Measure: Proportion of subjects who have a 6-point severity rating of 2 or 3, or use any ventilation or high-flow nasal cannula as procedures, on any day through Day 29. Time: Baseline to Day 29
Measure: Proportion of subjects admitted into an ICU on any day through Day 29 from AE eCRFs. Time: Baseline to Day 29
Measure: Proportion of subjects who have a 6-point severity rating of 3, 4, 5, or 6, are alive, and do not use invasive mechanical ventilation as a procedure at Day 15. The analogous definition is applied to Day 29. Time: Baseline at Day 15 and at Day 29
Measure: Proportion of subjects who have a 6-point severity rating of 4, 5 or 6, or use a low- or high-flow nasal, are alive, and do not use any ventilation at Day 15. The analogous definition is applied to Day 29. Time: Baseline at Day 15 and at Day 29
Measure: Difference between treatment groups in the mean 6-point severity rating at Day 29 Time: Baseline to Day 29
Measure: Number of days from baseline to the first day through Day 29 with any 6-point severity rating greater than baseline. Time: Baseline to Day 29
Measure: Number of days from baseline to the first of any 2 consecutive days through Day 29 with all SpO2/FiO2 ratios > 400 on both days. Time: Baseline to Day 29
Measure: Number of days from baseline to the first day through Day 29 with ≥ 1-point decrease in any NEWS2 score from baseline. Time: Baseline to Day 29
Measure: Number of days from baseline to the first day through Day 29 with all NEWS2 scores < 2 on that day. Time: Baseline to Day 29
Measure: Mean change from baseline in NEWS2 score at Days 15 and 29 for subjects who are alive at these time points Time: Baseline at Day 15 and at Day 29.
Measure: Proportion of subjects who have a 6-point severity rating of 5 or 6, are alive, and do not use supplemental oxygen as a procedure at Day 15. Time: Baseline to Day 15
Measure: Proportion of subjects who are discharged from the hospital, have a 6-point severity rating of 6 on any day after discharge, and use supplemental oxygen on any day after discharge. Time: Baseline to Day 60
Measure: Mean number of days with respiratory rate > 24 breaths/minute through Day 29 for subjects who are alive at Day 29 and do not use invasive mechanical ventilation. Time: Baseline to Day 29
Measure: Mean number of days with supplemental oxygen use through Day 29 for subjects who are alive at Day 29. A day in which any 6-point severity rating is 2, 3, or 4, or supplemental oxygen is used as a procedure counts. Time: Baseline to Day 29
Measure: Number of days from baseline to the first day through Day 29 on which any SpO2 ≥ 90%, any 6-point severity rating is 5 or 6, and no supplemental oxygen is used as a procedure. Time: Baseline to Day 29
Measure: Mean number of ventilator-free days through Day 29 for subjects who are alive at Day 29. Time: Baseline to Day 29
Measure: Mean SOFA total scores at ICU admission and Day 29 (if still in ICU), from SOFA and AE eCRFs. Time: Baseline to Day 29
Measure: Mean number of days of hospitalization through Day 29 for subjects who are alive on Day 29. All days on study on or before hospitalization discharge are days of hospitalization, from 6-point severity rating scale eCRFs Time: Baseline to Day 29
Measure: Number of days from baseline to the first of any 2 consecutive days through Day 29 in which all temperatures show lack of fever on both days and no antipyretics are used on either day. Time: Baseline to Day 29
Measure: Number of subjects with deaths, SAEs, severe AEs, and Grade 3 or 4 laboratory test abnormalities at any time on study. Time: Screening to Day 60
Measure: Number and percentage of subjects with severe or life-threatening bacterial, invasive fungal, or opportunistic infections at any time through Day 29 from AE/SAE eCRFs. Time: Baseline to Day 29
Measure: Number and percentage of subjects with intranasal administration reactions at any time through Day 29 from AE/SAE eCRFs. Time: Baseline to Day 29
Measure: Proportion of subjects with ≥ 50% reduction in eGFR from baseline at any time on study from laboratory test eCRFs. Time: Baseline to Day 60
