Clinical trial NCT04346615: Safety and Efficacy Trial of Zavegepant* Intranasal for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: COVID-19 Infection
Keywords: COVID-19
COVID
Coronavirus
Biohaven
Intranasal
SARS-CoV-2
BHV-3500
Zavegepant
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-04-15
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mean 6 Point Ordinal Severity Rating Scale (6POSRS) Score at Day 15
timeFrame: Day 15
Secondary outcomes:
measure: Percentage of Participants With a 6-Point Severity Rating of 5 or 6, Who Were Alive and Off Supplemental Oxygen at Day 29
timeFrame: Day 29
measure: 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
timeFrame: Up to Day 29
measure: Percentage of Participants Admitted Into an Intensive Care Unit (ICU) Through Day 29
timeFrame: Up to Day 29
measure: Number of Participants With On-Treatment Deaths, Serious Adverse Events (SAEs) and Severe Adverse Events (AEs)
timeFrame: From first dose of study treatment on Day 1 until Day 15
measure: Number of Participants With Grade 3 or 4 On-Treatment Laboratory Test Abnormalities
timeFrame: From first dose of study treatment on Day 1 until Day 15
measure: Number of Participants With Severe or Life-Threatening Bacterial, Invasive Fungal, or Opportunistic Infections Through Day 29
timeFrame: Up to Day 29
measure: Number of Participants With Intranasal Administration Reactions Through Day 29
timeFrame: Up to Day 29
measure: Percentage of Participants With >= 50% Reduction in Estimated Glomerular Filtration Rate (eGFR) From Baseline
timeFrame: From Baseline (Day 1) up to Day 15
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Hospital Research Pharmacy
state: District of Columbia
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Torresdale Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Roper Hospital
state: South Carolina
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: