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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04346615
Recruitment Status : Recruiting
First Posted : April 15, 2020
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Biohaven Pharmaceuticals, Inc.

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, 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.


Condition or disease Intervention/treatment Phase
COVID-19 Infection Drug: Vazegepant (BHV-3500) Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: BHV3500-203: Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of Zavegepant* (BHV-3500) Intranasal (IN) for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen
Actual Study Start Date : April 25, 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Oxygen Therapy

Arm Intervention/treatment
Experimental: Vazegepant
Vazegepant (BHV-3500) 10 mg intranasal (IN) Q8h for 14 days
Drug: Vazegepant (BHV-3500)
10 mg intranasal (IN) for 14 days

Placebo Comparator: Placebo
Placebo Q8h for 14 days
Drug: Placebo
Placebo Q8h for 14 days




Primary Outcome Measures :
  1. To evaluate efficacy of vazegepant (BHV-3500) compared with placebo in subjects hospitalized with COVID-19 infection requiring supplemental oxygen, using a six-point rating scale at Day 15. . [ Time Frame: Baseline to Day 15 ]

    a. Efficacy will be measured by the average between group difference on a 6-point, ordinal, severity rating scale at Day 15. The severity ratings are:

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Not hospitalized


Secondary Outcome Measures :
  1. The proportion of unique subjects alive and off of oxygen. These are subjects in categories 5 or 6 of the 6-point ordinal scale being used as the primary endpoint. [ Time Frame: Baseline to Day 29 ]
  2. A subject requiring initiation of invasive mechanical ventilation, non-invasive ventilation, or a high flow nasal cannula is a subject that has any eCRF showing the use of any such device on any day. [ Time Frame: Baseline to Day 60 ]
  3. The proportion of unique subjects admitted to an ICU verse those not admitted. [ Time Frame: Baseline to Day 60 ]
  4. Subjects are alive and respiratory-failure free if they are categorized as being in categories 3, 4, 5 or 6 of the 6-point ordinal scale being used as the primary endpoint. [ Time Frame: Baseline to Day 60 ]
  5. Subjects are alive and free of either invasive mechanical ventilation or non-invasive ventilation if they are categorized as being in categories 4, 5 or 6 of the 6-point ordinal scale being used as the primary endpoint. [ Time Frame: Baseline to Day 60 ]
  6. Efficacy on Day 29 will be evaluated using the same 6-point severity scales that is used at Day 15. [ Time Frame: Baseline at Day 15 and at Day 29 ]
  7. Time to improvement of one category on the 6-point severity scale will be determined as the number of days from baseline to the first day that an eCRF indicates a one category improvement in the scale. [ Time Frame: Baseline to Day 60 ]
  8. A 48-hour improvement in SpO2/FiO2 ratio consists of two consecutive days where the case report forms show a clinically meaningful increase from baseline. [ Time Frame: Baseline to Day 60 ]
  9. The time to improvement in the in the NEWS2 scale will be determined as the number of days from baseline to the first eCRF that shows an improvement. [ Time Frame: Baseline to Day 29 ]
  10. A score < 2 for 24 hours on the NEWS2 scale consists of a day where all of the reported NEWS2 scores are < 2. [ Time Frame: Baseline to Day 29 ]
  11. The change in NEWS2 scores will be determined as the change from baseline at Day 15 and at Day 29. [ Time Frame: Baseline at Day 15 and at Day 29. ]
  12. The proportion of unique subjects alive and off of oxygen. [ Time Frame: Baseline to Day 60 ]
  13. The proportion of subjects discharged to home on supplemental oxygen will determined from the unique number of subjects have eCRF pages indicating they were discharged to home while still on supplemental oxygen. [ Time Frame: Baseline to Day 60 ]
  14. A day with a resting respiratory rate > 24 is a day in which all eCRFs collected for a subject indicate observed respiratory rates > 24 breaths per minute. [ Time Frame: Baseline to Day 29 ]
  15. A day with supplemental oxygen is one in which any case report form collected on that day indicates the use of any amount of supplemental oxygen. [ Time Frame: Baseline to Day 29 ]
  16. Time to saturation greater than or equal to 90% on room air is measured by the number of days from baseline to the first day on which an eCRF indicates saturation greater than or equal to 90% without any supplemental oxygenation. [ Time Frame: Baseline to Day 60 ]
  17. A ventilator free day is a day in which all of the eCRFs collected indicate that the subject was not using a ventilator. [ Time Frame: Baseline to Day 29 ]
  18. SOFA scores will be determined from eCRFs. Values will be determined for subjects at admission to an ICU and for all subjects still in an ICU at the end of the study (Day 29). [ Time Frame: Baseline to Day 29 ]
  19. The number of days of hospitalization will be determined from eCRFs. A hospitalization day is any day that it is shown that a subject spent at least spent part of the day in a hospital. [ Time Frame: First day of hospital admission to discharge from hospital (evaluated from Baseline to Day 60) ]
  20. Time to fever resolution, without antipyretics, during two contiguous days . [ Time Frame: Screening to 48 hours fever free ]
  21. The number of deaths, SAEs, severe AEs and Grade 3 or 4 laboratory abnormalities will be tabulated as the number of unique subjects meeting those criteria. [ Time Frame: Screening to Day 60 ]
  22. The incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infections will be tabulated as the number of unique subjects, reported in eCRFs, as having these conditions at any point in the study [ Time Frame: Screening to day 60 ]
  23. The incidence of intranasal administration reactions will be tabulated, from eCRFs, as the number of unique subjects having such a condition at any point in the study. [ Time Frame: Baseline to Day 60 ]
  24. The proportion of subjects who develop significant renal disease. [ Time Frame: Baseline to Day 60 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04346615


Contacts
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Contact: Elyse Stock, MD 203-404-0410 clinicaltrials@biohavenpharma.com

Locations
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United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Maximiliano Menna    202-444-0371    Mpm229@georgetown.edu   
United States, Pennsylvania
Thomas Jefferson University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Agbenu Amali    215-503-8954    Agbenu.Amali@Jefferson.edu   
Sponsors and Collaborators
Biohaven Pharmaceuticals, Inc.
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Responsible Party: Biohaven Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04346615    
Other Study ID Numbers: BHV3500-203
First Posted: April 15, 2020    Key Record Dates
Last Update Posted: July 1, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biohaven Pharmaceuticals, Inc.:
COVID-19
COVID
Coronavirus
Biohaven
Intranasal
SARS-CoV-2
BHV-3500
Vazegepant