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

NCT05717062 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: OPX-PR-03FD-R-7839
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 10

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

Conditions

Snakebite; Envenoming, Snake

Keywords

Envenoming, Snakebite, varespladib; antidote; snake

Outcome Measures

Primary Outcomes (2)

• For subjects bitten by vipers: Area Under the Curve (AUC) of an abbreviated Snakebite Severity Score

  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.

  Baseline to Day 14

• For subjects bitten by elapids: Time to complete head-lift recovery defined by a 5-second head-lift of 5 seconds.

  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.

  Baseline to Day 14

Secondary Outcomes (5)

• 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

• Patient Specific Functional Scale (PSFS) score at Day 3 and Day 7.

  Day 3 and Day 7

• Complete Snakebite Severity Scale Score (SSS) recovery, from baseline to Day 28.

  Baseline through Day 28

• 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

Study Arms (2)

Varespladib Intravenous Form (IV) + Varespladib Oral tablet (LY315920) + SOC

EXPERIMENTAL

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.

Drug: Varespladib intravenous form; Drug: varespladib-methyl- oral form

Placebo Intravenous (IV) + Placebo Oral + SOC

ACTIVE COMPARATOR

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.

Drug: Placebo intravenous form; Drug: Placebo - oral form

Interventions

Varespladib intravenous form DRUG

This is a lyophilized drug contained in 100 mg vials to be reconstituted in Water for Injection (WFI), followed by dilution into 0.9% Sodium Chloride Injection.

Also known as: LY315920

Varespladib Intravenous Form (IV) + Varespladib Oral tablet (LY315920) + SOC

varespladib-methyl- oral form DRUG

Varespladib-methyl (LY333013) is an immediate-release, oval, white, film-coated tablet at a dosage strength of 250 mg for oral administration.

Also known as: LY333013

Varespladib Intravenous Form (IV) + Varespladib Oral tablet (LY315920) + SOC

Placebo intravenous form DRUG

The intravenous placebo will be saline (0.9%). Blinding will be ensured by covering the bag containing the investigational product with opaque covers.

Placebo Intravenous (IV) + Placebo Oral + SOC

Placebo - oral form DRUG

Oral placebo is supplied as a white film-coated oval tablet to match the appearance of the LY333013 250 mg tablet and contains a subset of the excipients present in the active tablet formulation: lactose monohydrate, microcrystalline cellulose, and magnesium stearate

Placebo Intravenous (IV) + Placebo Oral + SOC

Eligibility Criteria

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

You may qualify if:

• Is a male or female ≥ 18 years of age with venomous snakebite.
• Patients must have known or suspected venomous snakebite. In India, enrollment will be restricted to patients bitten by suspected or confirmed Russell's viper (Daboia russelii) or krait (Bungarus spp.) In the U.S., any snakebite that meets all other criteria may be eligible.
• Category 1: The participant is enrolled within 5 hours of venomous snakebite or symptom onset with an SSS score of ≥2 in one system and ≥1 in another system (2+1).
• Category 2: The participant has a suspected or confirmed bite from an elapid and is enrolled within 10 hours of bite or symptom onset with moderate to severe cranial nerve or skeletal muscle weakness.
• Is willing (or legally authorized representative is willing) to provide informed consent prior to initiation of any study procedures.

You may not qualify if:

• Has history of or is suspected to have CVA or intracranial bleeding of any kind, acute coronary syndrome, MI, or severe pulmonary hypertension.
• Has known history of inherited bleeding or coagulation disorder.
• Is, at Screening Visit, using the following anticoagulants: warfarin/coumadin, argatroban, bilvalirudin, lepirudin, apixaban, dabigatran, clopidogrel, prasugrel, ticlodipine or another anticoagulant agent not specifically listed, or has used heparin, enoxaparin, fondaparinux, or other low molecular weight heparin or any antiarrhythmic drugs within 14 days prior to treatment.
• Has a history of chronic liver disease such as chronic active viral hepatitis, alcohol- related liver disease, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis.
• Reports or has known pre-existing renal impairment or chronic kidney disease.
• Has a known allergy or significant adverse reaction to varespladib or varespladib-methyl.
• Is considered by the Investigator to be unable to comply with protocol requirements due to geographic considerations, psychiatric disorders, or other compliance concerns.
• Is pregnant, has a positive serum human chorionic gonadotropin (hCG) pregnancy test or not willing to use a highly effective method of contraception for 14 days after initial treatment, or is breast-feeding.

Sponsors & Collaborators

• Ophirex, Inc.: lead

Study Sites (10)

Banner University Medical Center - Phoenix

Phoenix, Arizona, 85006, United States

Location

Arizona Poison & Drug Information Center

Tucson, Arizona, 85721, United States

Location

Desert Regional Medical Center

Palm Springs, California, 92262, United States

Location

Antelope Valley Medical Center

Rosamond, California, 93560, United States

Location

UF Health Shands Hospital

Gainesville, Florida, 32610, United States

Location

University of South Florida/Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Emergency Medicine, University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Texas Tech University Health Sciences Center El Paso

El Paso, Texas, 79905, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Snake Bites

Interventions

varespladib; varespladib methyl

Condition Hierarchy (Ancestors)

Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Study Officials

• Timothy Platts-Mills, MD, MSc

  Ophirex, Inc.

  PRINCIPAL INVESTIGATOR

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: January 20, 2023
• First Posted: February 8, 2023
• Study Start: May 30, 2023
• Primary Completion: November 28, 2024
• Study Completion: February 24, 2025
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)