A Phase 2 interventional study of Varespladib Methyl and Placebo in Snakebites, Envenoming and Envenoming, Snake, sponsored by Ophirex, Inc.. Completed at 16 sites in 2 countries. Open to participants aged 5 Years and older. Per ClinicalTrials.gov, last updated 2025-07-01.
Sponsored by Ophirex, Inc. · Phase 2, Interventional, and Treatment
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.
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).
38 studies on the registry are indexed under Snake Bites; 11 are open to participants now.
This study's enrollment of 95 is above the median of 70 across 18 interventional studies indexed under Snake Bites.
Browse Snake Bites studies →Ophirex, Inc. is the lead sponsor of 3 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Is a male or female subject ≥ 5 years of age with venomous snakebite and must present with an initial SSS of
SSS scoring should be performed for inclusion assessment without waiting for receipt of Baseline hematological laboratory results. Gastrointestinal scores should not be used for inclusion.
Must meet one of two categories of inclusion criteria:
Category 1: The patient has not yet completed first dose of antivenom:
SSS inclusion score* of ≥2 in one system and ≥1 in another system (2+1) OR ≥3 in at least one system.
OR
Category 2: The patient has completed an initial dose of antivenom:
SSS inclusion score* of ≥2 in one system and ≥1 in another system (2+1) OR ≥3 in at least one system AND CGI-I score of ≥5 (i.e., minimally worse, much worse, or very much worse).
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Varespladib-methyl is an immediate-release (IR), oval, white, film-coated tablet at a dosage strength of 250 mg for oral administration. Scaled pediatric doses of varespladib-methyl are supplied as 50 mg IR capsules for oral administration. Adult subjects will receive an initial loading dose of 500 mg (2 × 250 mg oral tablet) varespladib-methyl upon randomization, followed by dosing with 250 mg varespladib-methyl (1 × 250 mg oral tablet) approximately 12 hours later, and subsequent twice daily (BID) dosing with 1 × 250 mg varespladib-methyl oral tablets for the remainder of the 7-day treatment period. Tablets may be administered via naso- or orogastric tubes in patients requiring mechanical ventilation. Pediatric subjects (5 to \< 18 years) will be administered doses of varespladib-methyl determined by allometric scaling, provided as 50 mg capsules. Age-appropriate capsules may be administered via naso- or orogastric tubes in patients requiring mechanical ventilation.
Drug: Varespladib Methyl · Drug: Standard of care (SOC)
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 immediate-release capsule to match the varespladib-methyl 50 mg capsule, and contains the excipients lactose monohydrate, microcrystalline cellulose, and magnesium stearate. The dosing of placebo will match that of varespladib-methyl.
Drug: Placebo · Drug: Standard of care (SOC)
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.
Also known as: LY333013
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.
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.
Change in the Combined Pulmonary, Cardiovascular, Hematologic, Nervous System, and Renal Subscores of the Snakebite Severity Score (SSS)
Change from baseline (pre-dosing) to 6 and 9 hours after the first dose, in the combined pulmonary, cardiovascular, hematologic symptoms, nervous system, and renal subscores of the SSS. The values from each of these subscores will be totaled. The average of the 6- and 9-hour scores will be used as the post-treatment value. The Snakebite Severity Scale (SSS) is a tool used to measure the severity of envenoming based on up to 7 body categories: pulmonary, cardiovascular, gastrointestinal, nervous, and renal system (graded at levels from Grade 0 to Grade 3), local wound, and hematological, (graded at levels from Grade 0 to Grade 4). A higher score indicates worse symptoms. The minimum score for the five item SSS is 0 and the maximum score is 16, with the higher score indicating worse symptoms. For the primary outcome we are focusing only on 5 subscores, that does not include the local wound nor the gastrointestinal subscores.
Time frame: Baseline to 6 and 9 hours after first dose
Area Under the Curve (AUC) of the Local Wound, Pulmonary, Cardiovascular, Hematologic Symptoms, Renal, and Nervous System Sections of the SSS
Baseline (pre-dosing) through Day 7 in the AUC of the local wound, pulmonary, cardiovascular, hematologic symptoms, nervous, and renal system sections of the SSS. The Snakebite Severity Scale (SSS) is a tool used to measure the severity of envenoming based on 7 body categories: pulmonary, cardiovascular, gastrointestinal, nervous, and renal effects (graded at levels from Grade 0 to Grade 3), local wound and hematological, (graded at levels from Grade 0 to Grade 4). A higher score indicates worse symptoms. The maximum score for the SSS is 23. For this outcome, the maximum score is 20 and if this score was present for the entire first week (168 hours) the maximum AUC is 3,370. The minimum AUC is a score of 3 at baseline and a score of 0 at three hours, which gives an AUC of 5.25.
Time frame: Baseline through Day 7
Area Under the Curve (AUC) of the Numeric Pain Rating Scale (NPRS)
Numeric Pain Rating Scale is a scale that goes from 0 to 10 with 10 being the worst possible pain. This measure is an AUC measure that is calculated from 0 to 48 hours using trapezoidal function in which the mean score for any given 2 periods of time is multiplied by the elapsed duration of time between those two periods. Each of these mean scores are summed to calculate the AUC. The minimum score is 0 and the maximum is 480.
Time frame: From Baseline through Day 3
Clinician Global Impression - Improvement
Clinician Global Impression - Improvement focus on improvement for Day 2. The scale is a 1 to 7 score with 1 indicating very much improved and 7 indicating very much worse.
Time frame: Day 2
All-cause Mortality
The number of patients experiencing the event (death). The all-cause mortality will be censored at Day 60.
Time frame: Baseline through Day 28
Patient-Specific Functional Scale (PSFS) Score
PSFS total score on Day 7. The PSFS is a 3-item instrument which assesses functional abilities. The total score ranges from 0 to 10 with a lower score indicating greater functional difficulties.
Time frame: Day 7
Numeric Pain Rating Scale (NPRS) Score
Change from baseline (pre-dosing) through Day 28 in NPRS score in patients able to respond pre-dosing through Day 28. The Numeric Pain Rating Scale is an 11-point scale for patient self-reporting of pain with scores ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Baseline through Day 28
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation of Investigational Product (IP)
Adverse events will be assessed from the time of signing informed consent to 28 days after initiating study drug.
Time frame: 28 Days after the initiation of study drug
| Milestone | Varespladib-methyl | Placebo |
|---|---|---|
| Started | 45 | 50 |
| Completed | 41 | 43 |
| Not completed | 4 | 7 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Withdrawal by subject | 4 | 3 |
| Withdrew: 1 left ama | 0 | 1 |
| Withdrew: Subject changed hospitals | 0 | 1 |
| Withdrew: Unable to complete due to work | 0 | 1 |
Change from baseline (pre-dosing) to 6 and 9 hours after the first dose, in the combined pulmonary, cardiovascular, hematologic symptoms, nervous system, and renal subscores of the SSS. The values from each of these subscores will be totaled. The average of the 6- and 9-hour scores will be used as the post-treatment value. The Snakebite Severity Scale (SSS) is a tool used to measure the severity of envenoming based on up to 7 body categories: pulmonary, cardiovascular, gastrointestinal, nervous, and renal system (graded at levels from Grade 0 to Grade 3), local wound, and hematological, (graded at levels from Grade 0 to Grade 4). A higher score indicates worse symptoms. The minimum score for the five item SSS is 0 and the maximum score is 16, with the higher score indicating worse symptoms. For the primary outcome we are focusing only on 5 subscores, that does not include the local wound nor the gastrointestinal subscores.
| Snakebite Severity Score | Varespladib-methyl | Placebo |
|---|---|---|
| Change in the Combined Pulmonary, Cardiovascular, Hematologic, Nervous System, and Renal Subscores of the Snakebite Severity Score (SSS) | 1.1 ± 0.3 | 1.5 ± 0.2 |
Baseline (pre-dosing) through Day 7 in the AUC of the local wound, pulmonary, cardiovascular, hematologic symptoms, nervous, and renal system sections of the SSS. The Snakebite Severity Scale (SSS) is a tool used to measure the severity of envenoming based on 7 body categories: pulmonary, cardiovascular, gastrointestinal, nervous, and renal effects (graded at levels from Grade 0 to Grade 3), local wound and hematological, (graded at levels from Grade 0 to Grade 4). A higher score indicates worse symptoms. The maximum score for the SSS is 23. For this outcome, the maximum score is 20 and if this score was present for the entire first week (168 hours) the maximum AUC is 3,370. The minimum AUC is a score of 3 at baseline and a score of 0 at three hours, which gives an AUC of 5.25.
| Snakebite severity score X hours | Varespladib-methyl | Placebo |
|---|---|---|
| Area Under the Curve (AUC) of the Local Wound, Pulmonary, Cardiovascular, Hematologic Symptoms, Renal, and Nervous System Sections of the SSS | 421 ± 45 | 430 ± 44 |
Numeric Pain Rating Scale is a scale that goes from 0 to 10 with 10 being the worst possible pain. This measure is an AUC measure that is calculated from 0 to 48 hours using trapezoidal function in which the mean score for any given 2 periods of time is multiplied by the elapsed duration of time between those two periods. Each of these mean scores are summed to calculate the AUC. The minimum score is 0 and the maximum is 480.
| scores on a scale * hours | Varespladib-methyl | Placebo |
|---|---|---|
| Area Under the Curve (AUC) of the Numeric Pain Rating Scale (NPRS) | 170 ± 17 | 173 ± 18 |
Clinician Global Impression - Improvement focus on improvement for Day 2. The scale is a 1 to 7 score with 1 indicating very much improved and 7 indicating very much worse.
| score on a scale | Varespladib-methyl | Placebo |
|---|---|---|
| Clinician Global Impression - Improvement | 2.3 ± 0.2 | 2.4 ± 0.2 |
The number of patients experiencing the event (death). The all-cause mortality will be censored at Day 60.
| Participants | Varespladib-methyl | Placebo |
|---|---|---|
| All-cause Mortality | 0 | 0 |
PSFS total score on Day 7. The PSFS is a 3-item instrument which assesses functional abilities. The total score ranges from 0 to 10 with a lower score indicating greater functional difficulties.
| score on a scale | Varespladib-methyl | Placebo |
|---|---|---|
| Patient-Specific Functional Scale (PSFS) Score | 5.89 ± 0.29 | 5.86 ± 0.29 |
Change from baseline (pre-dosing) through Day 28 in NPRS score in patients able to respond pre-dosing through Day 28. The Numeric Pain Rating Scale is an 11-point scale for patient self-reporting of pain with scores ranging from 0 (no pain) to 10 (worst possible pain).
| score on a scale | Varespladib-methyl | Placebo |
|---|---|---|
| Numeric Pain Rating Scale (NPRS) Score | 6.4 ± 0.2 | 6.1 ± 0.2 |
Adverse events will be assessed from the time of signing informed consent to 28 days after initiating study drug.
| Participants | Varespladib-methyl | Placebo |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation of Investigational Product (IP) | 19 | 28 |
Collected over Death was assessed up to 60 days, all other adverse events were assessed up to 28 Days after initiation of study drug.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Varespladib-methyl | 0/45 (0%) | 1/45 (2.2%) | 19/45 (42.2%) |
| Placebo | 0/50 (0%) | 0/50 (0%) | 28/50 (56%) |
| Event | Varespladib-methyl | Placebo |
|---|---|---|
| HypotensionVascular disorders | 1/45 | 0/50 |
| Event | Varespladib-methyl | Placebo |
|---|---|---|
| Abnormal labsBlood and lymphatic system disorders | 7/45 | 7/50 |
| Nausea and vomitingGastrointestinal disorders | 3/45 | 7/50 |
| headacheNervous system disorders | 2/45 | 5/50 |
| InfectionsInfections and infestations | 2/45 | 5/50 |
| Anemia and ThrombocytopeniaBlood and lymphatic system disorders | 3/45 | 3/50 |
| DizzinessNervous system disorders | 2/45 | 1/50 |
| Age, Categorical(Participants) | Varespladib-methyl | Placebo | Total |
|---|---|---|---|
| <=18 years | 6 | 4 | 10 |
| Between 18 and 65 years | 33 | 43 | 76 |
| >=65 years | 6 | 3 | 9 |
| Age, Continuous(years) | Varespladib-methyl | Placebo | Total |
|---|---|---|---|
| Mean | 37.6 ± 18.6 | 41.9 ± 15.9 | 39.9 ± 17.3 |
| Sex: Female, Male(Participants) | Varespladib-methyl | Placebo | Total |
|---|---|---|---|
| Female | 10 | 11 | 21 |
| Male | 35 | 39 | 74 |
| Ethnicity (NIH/OMB)(Participants) | Varespladib-methyl | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 2 | 3 |
| Not Hispanic or Latino | 41 | 47 | 88 |
| Unknown or Not Reported | 3 | 1 | 4 |
| Race (NIH/OMB)(Participants) | Varespladib-methyl | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 1 |
| Asian | 30 | 30 | 60 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 2 | 4 |
| White | 10 | 17 | 27 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 2 | 1 | 3 |
| Region of Enrollment(participants) | Varespladib-methyl | Placebo | Total |
|---|---|---|---|
| United States | 14 | 19 | 33 |
| India | 31 | 31 | 62 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Aug 2021 to primary completion in Jun 2023, 21 months.
Results were first posted in Jul 2025, 2 years after primary completion.
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Studies of the drug tested here: Varespladib methyl