NCT04996264

Broad-spectrum Rapid Antidote: Varespladib Oral for Snakebite

Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of a Multi-Dose Regimen of Oral Varespladib-Methyl in Subjects Bitten by Venomous Snakes

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 95 (actual)
• Sponsor: Ophirex, Inc. · Industry
• Sex: All
• Age: 5 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

This is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study designed to evaluate the safety, tolerability, and efficacy of varespladib-methyl, concurrently with SOC, in subjects bitten by venomous snakes. Approximately 110 male and female eligible subjects will be enrolled and randomized to receive active varespladib-methyl or placebo (in addition to SOC) in a 1:1 ratio (approximately 36 per group). There will be no stratification by type of snakebite, though randomization will be stratified by age group (5 to 11 years, 12 to 17 years, and ≥ 18 years) and by the presence or absence of severe neurologic symptoms defined by yes/no neurologic system subscore of the snakebite severity score of ≥ 2. Effective treatments for snakebite envenoming represents a deadly and unmet global medical need. While antivenoms comprise the SOC for treatment of snakebites, they suffer from several limitations including specificity of each antivenom for specific species of snake, limited access to antivenom in rural areas, practical storage requirements, and delays in administration. Treatment of snakebite envenoming with the small-molecule drug varespladib-methyl, which targets secreted phospholipase A₂ (sPLA₂) present in more than 95% of snake venoms, has the potential to overcome several limitations of serum-based antivenoms that underpin traditional SOC. This study in the United States and India will provide coverage of a broad spectrum of venomous snake genera, including elapids, pit vipers, and potentially exotics such as vipers and colubrids if encountered over the course of the study. The study is designed to cover differing geographies and differing sPLA₂ structures. Study sites have been and will be selected based on demonstrated historical incidence of snake bites from species deemed relevant to this study, to ensure a broad range of envenoming toxins are expected to be encountered in potential study subjects. The study design allows for both treatment arms (varespladib-methyl and placebo) to receive SOC (e.g., antivenom) concurrently. Thus, critically ill adult and pediatric subjects may receive emergency treatment in a timely manner while being evaluated for the potential clinical benefit associated with inhibition of venom sPLA₂ and inflammatory sPLA2s by varespladib-methyl. Because subjects with severe snakebites are admitted to emergency departments, this study was designed to screen, enroll, and administer treatment in a single visit at the hospital upon admission. Because varespladib-methyl is administered orally, subjects who demonstrate substantial improvement and are eligible for discharge from the hospital may continue investigational product treatment in an outpatient setting. Risks associated with the control (placebo) arm of this study include the same risks associated with SOC (antivenom).

Conditions

• Snakebites
• Envenoming
• Envenoming, Snake
• Envenomation, Snake

Interventions

Type	Name	Description
DRUG	Varespladib Methyl	Varespladib-methyl (LY333013) is an IR, oval, white, film-coated tablet at a dosage strength of 250 mg for oral administration. Scaled pediatric doses of varespladib-methyl (LY333013) are supplied as 50 mg IR capsules for oral administration.
DRUG	Placebo	The oral placebo is supplied as a white film-coated oval tablet to match the appearance of the varespladib-methyl 250 mg tablet and contains a subset of the excipients present in the active tablet formulation: lactose monohydrate, microcrystalline cellulose, and magnesium stearate. Placebo for scaled pediatric dosing is supplied as an IR capsule to match the varespladib-methyl 50 mg capsule, and contains the excipients lactose monohydrate, microcrystalline cellulose, and magnesium stearate.
DRUG	Standard of care (SOC)	SOC (including antivenom) will continue to be administered throughout the subject's participation in the study according to the protocol and the judgment of the Investigator.

Timeline

• Start date: 2021-08-15
• Primary completion: 2023-06-07
• Completion: 2023-06-08
• First posted: 2021-08-09
• Last updated: 2025-07-01
• Results posted: 2025-07-01

Locations

16 sites across 2 countries: United States, India

Regulatory

• FDA-regulated drug study