Safety and Efficacy Trial of Zavegepant* Intranasal for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen

BHV3500-203: Phase 2/3: Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of Zavegepant (BHV-3500) Intranasal (IN) for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen

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, Acute respiratory distress syndrome (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.

Study Overview

• Status: Terminated
• Conditions: COVID-19 Infection
• Intervention / Treatment: Drug: Zavegepant (BHV-3500); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital Research Pharmacy
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19114
      • Jefferson Torresdale Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects must provide informed consent in accordance with requirements of the study center's institutional review board (IRB) or eithics committee prior to the initiation of any protocol-required procedures
2. Subjects must agree to provide all requested demographic information (i.e. gender, race)
3. Subjects must be able to read and understand English or Spanish
4. Subjects must be over the age of 18 years
5. Subjects must have laboratory-confirmed SARS-CoV-2 infection as determined by PCR-based commercial or public health assay
6. Subjects must have symptoms that require hospitalization with supplemental oxygen and / or non-invasive ventilation as determined by the admitting physician. The maximum nasal cannula O2 concentration should be determined by the treating clinician and the limitations of the specific equipment
7. Subjects must be willing and able to comply with study-related procedures/assessments

Exclusion Criteria:

1. Subjects in immediate need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
2. Subjects with an eGFR < 30 mL/min, at the Screening Visit
3. Prisoners or subjects who are involuntarily incarcerated
4. Subjects who are participating in any other investigational clinical trial while participating in this clinical trial
5. Subjects who are under the age of 18 years
6. Subjects who are pregnant (all potential female enrollees need to have a negative pregnancy test prior to IP administration)
7. Subjects with multi-organ failure
8. Subjects who have received more than 48 hours of supplemental oxygen prior to randomization
9. Subjects with prior significant pulmonary disease (e.g., severe COPD/ILD/CHF/IPF) are excluded
10. Subjects receiving investigational therapies as part of a formal clinical trial for the treatment of COVID-19. During the course of this study, investigational therapies that may become "standard of care" to treat COVID-19, but are not part of a clinical trial, are allowed
11. Subjects who are on long-acting CGRP monoclonal antibodies will be excluded including Aimovig (erenumab), Emgality (galcanezumab), Ajovy (fremanezumab), and Vyepti (eptinezumab). Additionally, the investigational oral CGRP receptor antagonist, atogepant, that is taken daily will also be excluded. Oral CGRP receptor antagonists, Nurtec ODT (rimegepant) and Ubelvy (ubrogepant) that are typically used PRN infrequently will not be excluded as long the subject was not taking them on a daily basis and does not take them during the current study
12. Subjects who are unlikely to survive for more than 48 hours from the Screening Visit
13. Subjects with any of the following abnormal laboratory values at screening: aspartate AST or ALT greater than 5x ULN or bilirubin greater than 2x ULN
14. Subjects with known active TB, history of incompletely treated TB, suspected or known extrapulmonary TB
15. Subjects with suspected or known systemic bacterial or fungal infections. However, empiric antibiotics are permitted.
16. Subjects who have participated in any clinical research study evaluating an IP or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit
17. Subjects with any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the subject by their participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zavegepant; Zavegepant (BHV-3500) 10 mg intranasal (IN) dosed every 8 hours (3 times/day) (Q8h) for 14 days	Drug: Zavegepant (BHV-3500); 10 mg intranasal (IN) for 14 days
Placebo Comparator: Placebo; Placebo Q8h for 14 days Subjects dosed every 8 hours; 3 times/day (Q8h)	Drug: Placebo; Placebo Q8h for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 6 Point Ordinal Severity Rating Scale (6POSRS) Score at Day 15	The 6POSRS score was used to assess severity and ranged from 1 to 6 where: 1= Death; 2= Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), 3= Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 4= Hospitalized, requiring supplemental oxygen; 5= Hospitalized, not requiring supplemental oxygen and 6= not hospitalized. A higher score indicated a better outcome.	Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a 6-Point Severity Rating of 5 or 6, Who Were Alive and Off Supplemental Oxygen at Day 29	Percentage of participants who were alive and had a 6POSRS rating of 5 (Hospitalized, not requiring supplemental oxygen) or 6 (not hospitalized) and did not use supplemental oxygen at Day 29 were reported in this outcome measure. Participants with missing 6POSRS rating at Day 29 had the last on-study 6POSRS rating before Day 29 used. Participants with >= 1 procedure day of supplemental oxygen use before Day 29 for an ongoing procedure were considered failures, i.e., not alive or not off of oxygen at Day 29. 95% confidence interval (CI) was based on exact Clopper and Pearson method.	Day 29
Percentage of Participants With a 6-Point Severity Rating of 2 or 3 or Required Initiation of Invasive Mechanical Ventilation, Non-Invasive Ventilation, or a High-Flow Nasal Cannula Through Day 29	Percentage of participants who had a 6POSRS rating of 2 (Hospitalized, on invasive mechanical ventilation or ECMO) or 3 (Hospitalized, on non-invasive ventilation or high-flow oxygen devices) or >= 1 procedure day of ventilation or high-flow nasal cannula use on study through Day 29 were reported in this outcome measure. Participants with missing 6POSRS rating at Day 29 had all available on-study 6POSRS ratings before Day 29 used. 95% CI was based on exact Clopper and Pearson method.	Up to Day 29
Percentage of Participants Admitted Into an Intensive Care Unit (ICU) Through Day 29	Percentage of participants admitted into an ICU on any day through Day 29 were reported in this outcome measure. 95% CI was based on exact Clopper and Pearson method	Up to Day 29
Number of Participants With On-Treatment Deaths, Serious Adverse Events (SAEs) and Severe Adverse Events (AEs)	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect; other important medical events. Severe AEs were AEs that interrupted usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. On-treatment was defined as the time on study drug.	From first dose of study treatment on Day 1 until Day 15
Number of Participants With Grade 3 or 4 On-Treatment Laboratory Test Abnormalities	The following laboratory parameters were assessed: eosinophils, hemoglobin, leukocytes, lymphocytes (high and low), neutrophils, platelets, alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium (high and low), creatine kinase, creatinine, glomerular filtration rate (GFR) estimated Modification of Diet in Renal Disease (MDRD), glucose (high and low), lactate dehydrogenase, potassium (high and low), sodium (high and low), urate, glucose (urine) and protein (urine). Laboratory abnormalities were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 for all parameters except glucose and uric acid. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 was used for grading glucose and uric acid. Grade 3=severe and grade 4=potentially life threatening. Number of participants with grade 3 or 4 laboratory abnormalities is reported.	From first dose of study treatment on Day 1 until Day 15
Number of Participants With Severe or Life-Threatening Bacterial, Invasive Fungal, or Opportunistic Infections Through Day 29	Number of participants with any severe or life-threatening bacterial, invasive fungal, or opportunistic infections through Day 29 is reported in this outcome measure. Severe= interrupted usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. Life threatening=Participant was at immediate risk of death from the event as it occurred; i.e., it did not include a reaction that if it had occurred in a more serious form might have caused death.	Up to Day 29
Number of Participants With Intranasal Administration Reactions Through Day 29	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational product and that did not necessarily have a causal relationship with this treatment. Number of participants with any adverse events associated with intranasal administration were reported in this outcome measure.	Up to Day 29
Percentage of Participants With >= 50% Reduction in Estimated Glomerular Filtration Rate (eGFR) From Baseline	Percentage of participants with >=50% reduction in eGFR from Baseline during on-treatment phase were reported in this outcome measure.	From Baseline (Day 1) up to Day 15

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2020
• Primary Completion (Actual): April 29, 2022
• Study Completion (Actual): April 29, 2022

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; COVID-19; COVID; Intranasal; Biohaven; BHV-3500; Zavegepant
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: BHV3500-203; C5301004 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No