Clinical trial NCT05717062: Broad-spectrum Rapid Antidote: Varespladib IV to Oral Trial for Snakebite (BRAVIO)
Official title: Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Intravenous Varespladib Followed by Oral Varespladib in Addition to Standard of Care in Subjects Bitten by Venomous Snakes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Snakebite
Envenoming, Snake
Keywords: Envenoming, Snakebite, varespladib
antidote
snake
Lead sponsor: Ophirex, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-08
Enrollment: 140
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: 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.

Eligibility criteria: INCLUSION CRITERIA:

1. Is a male or female ≥ 18 years of age with venomous snakebite.
2. 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.
3. Participants must meet one of two categories of inclusion criteria:

   1. 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).

      OR
   2. 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.
4. Is willing (or legally authorized representative is willing) to provide informed consent prior to initiation of any study procedures.

EXCLUSION CRITERIA:

1. Has history of or is suspected to have CVA or intracranial bleeding of any kind, acute coronary syndrome, MI, or severe pulmonary hypertension.
2. Has known history of inherited bleeding or coagulation disorder.
3. 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.
4. 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.
5. Reports or has known pre-existing renal impairment or chronic kidney disease.
6. Has a known allergy or significant adverse reaction to varespladib or varespladib-methyl.
7. Is considered by the Investigator to be unable to comply with protocol requirements due to geographic considerations, psychiatric disorders, or other compliance concerns.
8. 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.

Primary outcomes:
measure: For subjects bitten by vipers: Area Under the Curve (AUC) of an abbreviated Snakebite Severity Score
timeFrame: Baseline to Day 14
measure: For subjects bitten by elapids: Time to complete head-lift recovery defined by a 5-second head-lift of 5 seconds.
timeFrame: Baseline to Day 14
Secondary outcomes:
measure: 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.
timeFrame: Baseline to Day 7
measure: Patient Specific Functional Scale (PSFS) score at Day 3 and Day 7.
timeFrame: Day 3 and Day 7
measure: Complete Snakebite Severity Scale Score (SSS) recovery, from baseline to Day 28.
timeFrame: Baseline through Day 28
measure: Total Antivenom Requirement, measured in number of vials of antivenom administered to the subject, from baseline (pre-dosing) through Day 28
timeFrame: Baseline through Day 28
measure: Duration of Hospitalization from baseline (pre-dosing) through Day 28
timeFrame: Baseline through Day 28
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center - Phoenix
state: Arizona
city: Tucson
country: United States
facility: Arizona Poison & Drug Information Center
state: Arizona
city: Palm Springs
country: United States
facility: Desert Regional Medical Center
state: California
city: Rosamond
country: United States
facility: Antelope Valley Medical Center
state: California
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida/Tampa General Hospital
state: Florida
city: Lexington
country: United States
facility: Emergency Medicine, University of Kentucky
state: Kentucky
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center El Paso
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
Study officials:
affiliation: Ophirex, Inc.
name: Timothy Platts-Mills, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: