COVID-19 InfectionPhase 2/3NCT04346615
Safety and Efficacy Trial of Zavegepant* Intranasal for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen
A Phase 2/3 study testing Zavegepant (BHV-3500) in people with COVID-19 Infection, run by Pfizer at 6 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Infection
- What is being tested?
- Zavegepant (BHV-3500)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 6 sitesUnited States
- Study dates
- 25 Apr 2020to 29 Apr 2022
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 17Show fewer
- 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.
- 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
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Roper Hospital
Charleston, South Carolina, 29401
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Jefferson Torresdale Hospital
Philadelphia, Pennsylvania, 19114
Georgetown University Hospital Research Pharmacy
Washington D.C., District of Columbia, 20007
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
About this study
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
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
- Being tested
- Zavegepant (BHV-3500), Placebo
- Keywords
- COVID-19, COVID, Coronavirus, Biohaven, Intranasal, SARS-CoV-2, BHV-3500, Zavegepant
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zavegepant (BHV-3500)Drug
10 mg intranasal (IN) for 14 days
PlaceboDrug
Placebo Q8h for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Zavegepant | Experimental | Zavegepant (BHV-3500) 10 mg intranasal (IN) dosed every 8 hours (3 times/day) (Q8h) for 14 days Receives: Drug: Zavegepant (BHV-3500) |
| Placebo | Placebo comparator | Placebo Q8h for 14 days
Subjects dosed every 8 hours; 3 times/day (Q8h) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Baseline (Day 1) up to Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2020
- Study start25 Apr 2020
- Primary completion29 Apr 2022
- Study completion29 Apr 2022
Why it stopped: Lack of enrollment due to evolution of COVID-19 pandemic with reduction in patients at risk for severe disease and growing number of effective alternative therapies
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19 InfectionStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04346615
- Sponsor's protocol ID
- BHV3500-203
- Other IDs
- C5301004
- Status last verified
- Apr 2024
- First submitted
- 9 Apr 2020
- Last updated
- 2 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04346615
- Acronym / sponsor ID
- BHV3500-203
- Conditions
- COVID-19 Infection
- Keywords
- COVID-19, COVID, Coronavirus, Biohaven, Intranasal, SARS-CoV-2, BHV-3500, Zavegepant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment due to evolution of COVID-19 pandemic with reduction in patients at risk for severe disease and growing number of effective alternative therapies
- Enrolment
- 47 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 25 Apr 2020 (actual)
- Primary completion
- 29 Apr 2022 (actual)
- Study completion
- 29 Apr 2022 (actual)
- First posted
- 15 Apr 2020 (actual)
- Results
- Posted 2 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zavegepant | Experimental | Drug: Zavegepant (BHV-3500)Zavegepant (BHV-3500) 10 mg intranasal (IN) dosed every 8 hours (3 times/day) (Q8h) for 14 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo Q8h for 14 days Subjects dosed every 8 hours; 3 times/day (Q8h) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zavegepant (BHV-3500)10 mg intranasal (IN) for 14 days | Drug | Zavegepant |
| PlaceboPlacebo Q8h for 14 days | Drug | Placebo |
Primary outcome
Mean 6 Point Ordinal Severity Rating Scale (6POSRS) Score at Day 15
Time frame: 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.
8 secondary outcomes
Percentage of Participants With a 6-Point Severity Rating of 5 or 6, Who Were Alive and Off Supplemental Oxygen at Day 29
Time frame: 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
Time frame: Up to Day 29
Percentage of Participants Admitted Into an Intensive Care Unit (ICU) Through Day 29
Time frame: Up to Day 29
Number of Participants With On-Treatment Deaths, Serious Adverse Events (SAEs) and Severe Adverse Events (AEs)
Time frame: 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
Time frame: 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
Time frame: Up to Day 29
Number of Participants With Intranasal Administration Reactions Through Day 29
Time frame: Up to Day 29
Percentage of Participants With >= 50% Reduction in Estimated Glomerular Filtration Rate (eGFR) From Baseline
Time frame: From Baseline (Day 1) up to Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
Related trials for COVID-19 Infection
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Zavegepant (BHV-3500) in people with COVID-19 Infection, run by Pfizer at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean 6 Point Ordinal Severity Rating Scale (6POSRS) Score at Day 15 (time frame: Day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2024.