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

NCT04346615 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: BHV3500-203C5301004
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

COVID-19 Infection

Keywords

COVID-19; COVID; Coronavirus; Biohaven; Intranasal; SARS-CoV-2; BHV-3500; Zavegepant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Percentage of Participants With a 6-Point Severity Rating of 5 or 6, Who Were Alive and Off Supplemental Oxygen at Day 29

  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

  Up to Day 29

• Percentage of Participants Admitted Into an Intensive Care Unit (ICU) Through Day 29

  Up to Day 29

• Number of Participants With On-Treatment Deaths, Serious Adverse Events (SAEs) and Severe Adverse Events (AEs)

  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

  From first dose of study treatment on Day 1 until Day 15

Study Arms (2)

Zavegepant

EXPERIMENTAL

Zavegepant (BHV-3500) 10 mg intranasal (IN) dosed every 8 hours (3 times/day) (Q8h) for 14 days

Drug: Zavegepant (BHV-3500)

Placebo

PLACEBO COMPARATOR

Placebo Q8h for 14 days Subjects dosed every 8 hours; 3 times/day (Q8h)

Drug: Placebo

Interventions

Zavegepant (BHV-3500) DRUG

10 mg intranasal (IN) for 14 days

Zavegepant

Placebo DRUG

Placebo Q8h for 14 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Subjects must agree to provide all requested demographic information (i.e. gender, race)
• Subjects must be able to read and understand English or Spanish
• Subjects must be over the age of 18 years
• Subjects must have laboratory-confirmed SARS-CoV-2 infection as determined by PCR-based commercial or public health assay
• 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
• Subjects must be willing and able to comply with study-related procedures/assessments

You may not qualify if:

• Subjects in immediate need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
• Subjects with an eGFR \< 30 mL/min, at the Screening Visit
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are participating in any other investigational clinical trial while participating in this clinical trial
• Subjects who are under the age of 18 years
• Subjects who are pregnant (all potential female enrollees need to have a negative pregnancy test prior to IP administration)
• Subjects with multi-organ failure
• Subjects who have received more than 48 hours of supplemental oxygen prior to randomization
• Subjects with prior significant pulmonary disease (e.g., severe COPD/ILD/CHF/IPF) are excluded
• 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
• 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
• Subjects who are unlikely to survive for more than 48 hours from the Screening Visit
• 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
• Subjects with known active TB, history of incompletely treated TB, suspected or known extrapulmonary TB
• Subjects with suspected or known systemic bacterial or fungal infections. However, empiric antibiotics are permitted.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (6)

Georgetown University Hospital Research Pharmacy

Washington D.C., District of Columbia, 20007, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Jefferson Torresdale Hospital

Philadelphia, Pennsylvania, 19114, United States

Location

Roper Hospital

Charleston, South Carolina, 29401, United States

Location

Related Links

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

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquires@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 15, 2020
• Study Start: April 25, 2020
• Primary Completion: April 29, 2022
• Study Completion: April 29, 2022
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

US (6)