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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Ophirex, Inc.
- Enrollment
- 140
- Locations
- 10
- Primary Endpoint
- For subjects bitten by vipers: Area Under the Curve (AUC) of an abbreviated Snakebite Severity Score
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Varespladib Intravenous Form (IV) + Varespladib Oral tablet (LY315920) + SOC
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.
Intervention: Varespladib intravenous form (Drug)
Varespladib Intravenous Form (IV) + Varespladib Oral tablet (LY315920) + SOC
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.
Intervention: varespladib-methyl- oral form (Drug)
Placebo Intravenous (IV) + Placebo Oral + SOC
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.
Intervention: Placebo intravenous form (Drug)
Placebo Intravenous (IV) + Placebo Oral + SOC
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.
Intervention: Placebo - oral form (Drug)
Outcomes
Primary Outcomes
For subjects bitten by vipers: Area Under the Curve (AUC) of an abbreviated Snakebite Severity Score
Time Frame: 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.
Time Frame: 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 Outcomes
- 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)