Broad-spectrum Rapid Antidote: Varespladib IV to Oral Trial for Snakebite (BRAVIO)

Phase 2

Completed

Conditions: Snakebite
Envenoming, Snake

Interventions: Drug: Varespladib intravenous form
Drug: Placebo intravenous form
Drug: Placebo - oral form
Drug: varespladib-methyl- oral form

Registration Number: NCT05717062

Lead Sponsor: Ophirex, Inc.

Brief Summary: This is a multicenter,randomized,double-blind, placebo-controlled, phase 2 study designed to evaluate the safety, tolerability and efficacy of a continuous rate infusion (CRI) of IV varespladib followed by transition to the oral dosage form, varespladib-methyl, concurrently with SOC, in participants bitten by venomous snakes.

Note: Funding Source - FDA-OOPD

Detailed Description: This is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study designed to evaluate the safety, tolerability and efficacy of intravenous varespladib followed by oral varespladib, concurrently with standard of care (SOC), in participants bitten by venomous snakes.

Approximately 140 male and female eligible participants will be enrolled and randomized to receive active varespladib or placebo (in addition to SOC)

Randomization will be stratified by the presence or absence of neurotoxicity (SSS nervous system subscore of 0-1 or ≥ 2) at Baseline, and by receipt of antivenom prior to screening, resulting in 4 strata in total.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 140

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Varespladib Intravenous Form (IV) + Varespladib Oral tablet (LY315920) + SOC	Varespladib intravenous form	Participants will receive intravenous (IV) infusion of varespladib at dose of 0.45 milligrams per kilogram per hour (mg/kg/hr) for six hours. This infusion will continue until when the participant meets clinical criteria for transition to oral drug, -If criteria are met, they will be transitioned to varespladib-methyl (initial dose of 500 mg) then continued oral dosing q12 (once every 12 hours) of 250 mg for the remainder of the study period. Participants that do not meet the criteria for transitioning to the oral drug will remain on the IV infusion at 0.45 mg/kg/hr (along with SOC) and assessed twice a day until they meet criteria for transition to oral drug.
Placebo Intravenous (IV) + Placebo Oral + SOC	Placebo - oral form	Participants will receive intravenous (IV) infusion of placebo matched to varespladib for six hours. This infusion will continue until the participant meets clinical criteria for transition to oral drug. If criteria are met, they will be transitioned to the oral placebo then continued oral dosing for the remainder of the study period. Participants that do not meet the criteria for transitioning to the oral drug will remain on the IV infusion (along with SOC) and assessed twice a day until they meet criteria for transition to oral drug.
Varespladib Intravenous Form (IV) + Varespladib Oral tablet (LY315920) + SOC	varespladib-methyl- oral form	Participants will receive intravenous (IV) infusion of varespladib at dose of 0.45 milligrams per kilogram per hour (mg/kg/hr) for six hours. This infusion will continue until when the participant meets clinical criteria for transition to oral drug, -If criteria are met, they will be transitioned to varespladib-methyl (initial dose of 500 mg) then continued oral dosing q12 (once every 12 hours) of 250 mg for the remainder of the study period. Participants that do not meet the criteria for transitioning to the oral drug will remain on the IV infusion at 0.45 mg/kg/hr (along with SOC) and assessed twice a day until they meet criteria for transition to oral drug.
Placebo Intravenous (IV) + Placebo Oral + SOC	Placebo intravenous form	Participants will receive intravenous (IV) infusion of placebo matched to varespladib for six hours. This infusion will continue until the participant meets clinical criteria for transition to oral drug. If criteria are met, they will be transitioned to the oral placebo then continued oral dosing for the remainder of the study period. Participants that do not meet the criteria for transitioning to the oral drug will remain on the IV infusion (along with SOC) and assessed twice a day until they meet criteria for transition to oral drug.

Primary Outcome Measures

Name	Time	Method
For subjects bitten by vipers: Area Under the Curve (AUC) of an abbreviated Snakebite Severity Score	Baseline to Day 14	For subjects bitten by vipers: Area Under the Curve (AUC) of an abbreviated Snakebite Severity Score (SSS) composed of local wound, hematologic, and neurologic subscores from Baseline (pre-dosing) to Day 14. The independent p-values from subjects bitten by elapids and subjects bitten by vipers will be analyzed using Fisher's combined probability test to obtain a single global p-value for testing the primary endpoint. The Snakebite Severity Scale is a tool used to measure the severity of envenoming, a higher score indicates worse symptoms.
For subjects bitten by elapids: Time to complete head-lift recovery defined by a 5-second head-lift of 5 seconds.	Baseline to Day 14	The independent p-values from subjects bitten by elapids and subjects bitten by vipers will be analyzed using Fisher's combined probability test to obtain a single global p-value for testing the primary endpoint.

Secondary Outcome Measures

Name	Time	Method
Area under the curve of the composite outcome of pulmonary, cardiovascular, local wound, hematologic, renal, and nervous system sections of the SSS from Baseline to Day 7, among patients randomized within 5 hours from bite.	Baseline to Day 7	The SSS is a tool developed to measure the severity of snakebite envenoming. Each category is graded from 0 to 3 or 4 (depending on the body category) and a higher score indicates worse signs or symptoms.
Patient Specific Functional Scale (PSFS) score at Day 3 and Day 7.	Day 3 and Day 7	Patient Specific Functional Scale (PSFS) is a brief, interview-format questionnaire that is used to assess functional disability and any changes in performance of activities. The patient provides 3 activities. The patient then provides a rating for each item on an 11-item ordinal scale, where 0 is "unable to perform activity" and 10 is "able to perform activity at the same level as before injury or problem." The range of possible single activity scores is 0 to 10 and the range of possible total score is 0 to 10 (0 is unable to perform and 10 is perform as before injury/illness).
Complete Snakebite Severity Scale Score (SSS) recovery, from baseline to Day 28.	Baseline through Day 28	Complete snakebite severity score (SSS) recovery, defined as a composite score of 0 for the pulmonary, cardiovascular, local wound, hematologic, renal, and nervous system sections of the SSS at Day 28. The SSS is a tool developed to measure the severity of snakebite envenoming. Each category is graded from 0 to 3 or 4 (depending on the body category) and a higher score indicates worse signs or symptoms.
Total Antivenom Requirement, measured in number of vials of antivenom administered to the subject, from baseline (pre-dosing) through Day 28	Baseline through Day 28
Duration of Hospitalization from baseline (pre-dosing) through Day 28	Baseline through Day 28

Trial Locations

Locations (10): UF Health Shands Hospital
🇺🇸
Gainesville, Florida, United States
Banner University Medical Center - Phoenix
🇺🇸
Phoenix, Arizona, United States
University of South Florida/Tampa General Hospital
🇺🇸
Tampa, Florida, United States
Arizona Poison & Drug Information Center
🇺🇸
Tucson, Arizona, United States
Desert Regional Medical Center
🇺🇸
Palm Springs, California, United States
Antelope Valley Medical Center
🇺🇸
Rosamond, California, United States
Emergency Medicine, University of Kentucky
🇺🇸
Lexington, Kentucky, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Texas Tech University Health Sciences Center El Paso
🇺🇸
El Paso, Texas, United States
UT Health San Antonio
🇺🇸
San Antonio, Texas, United States