| CTRI Number |
CTRI/2021/11/037901 [Registered on: 10/11/2021] Trial Registered Prospectively |
| Last Modified On: |
12/07/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A study of Broad-spectrum Rapid Antidote: Varespladib Oral for Snakebite (BRAVO). |
Scientific Title of Study
Modification(s)
|
Randomized, Double-Blinded, Placebo-Controlled Add-On Therapy Study to Evaluate the Safety, Tolerability, and Efficacy of a Multi-Dose Regimen of Oral Varespladib-Methyl in Subjects Bitten by Venomous Snakes |
| Trial Acronym |
BRAVO |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| OPX-PR-01 V2.1 Dated 12OCT2021 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Matthew R Lewin |
| Designation |
Chief Medical Officer |
| Affiliation |
Ophirex Inc. |
| Address |
5643 Paradise Drive Suite 2
Corte Madera CA
94925
Other |
| Phone |
415-425-7892 |
| Fax |
|
| Email |
matt@ophirex.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Stephen Samuel |
| Designation |
Consulting VP, Clinical Medicine |
| Affiliation |
Ophirex Inc. |
| Address |
5643 Paradise Drive Suite 2
Corte Madera CA
94925
Other |
| Phone |
44-7825-180898 |
| Fax |
|
| Email |
stephen@ophirex.com |
|
Details of Contact Person
Public Query
|
| Name |
Mr Bhavesh Acharya |
| Designation |
Country Lead |
| Affiliation |
Premier Research Group India Pvt Ltd |
| Address |
Wework 13th Floor Salarpuria Magnificia
No 78 Doorvaninagar Old Madras Road
Bangalore
KARNATAKA
560016
India |
| Phone |
9886627694 |
| Fax |
|
| Email |
bhavesh.acharya@premier-research.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Ophirex Inc |
| Address |
5643 Paradise Drive #2
Corte Madera, CA 94925
(415) 891-8682 |
| Type of Sponsor |
Other [Public-Benefit Biotechnology Company] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
United States of America
India |
Sites of Study
Modification(s)
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Partha Pratim Mukherjee |
Calcutta National Medical College & Hospital |
Department of Medicine
32, Gorachand Road, Beniapukur,
Kolkata
WEST BENGAL |
9830488840
033-22897122
drppmukherjeecnmc@gmail.com |
| Dr Tushar Gopalkrishna |
Father Muller Medical College Hospital |
Hospital Building 1st floor, Room No. 37, Department of Medicine, Father Muller Road, Kankanady, Magaluru 575 002
Dakshina Kannada
KARNATAKA |
9742508204
gktushar96@gmail.com |
| Dr Vinod Khandait Yashwantrao |
Govt Medical College, Nagpur |
Hanuman Nagar, Ajni Rd, Medical Chowk, Ajni, Nagpur, Maharashtra 440003
Nagpur
MAHARASHTRA |
9373107740
drkhandait@rediffmail.com |
| Dr Neeraj Manikath |
Govt. Medical College, Kozhikode |
OPD Room No.65 Department of Medicine, Medical College Junction, 17, Mavoor Rd, near Police Station
Kozhikode
KERALA |
0949600510
nmanikath@gmail.com |
| Dr Chanaveerappa R Bammigatti |
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) |
Department of Medicine
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)
Dhanavantri Nagar,
Pondicherry
PONDICHERRY |
9488083674
4132272067
bammigatti@gmail.com |
| Dr Suneetha D K |
K R Hospital, attached to Mysore Medical College and Research Institute |
1st floor, Department of Medicine, Irwin Road,
Mysore
KARNATAKA |
9845585413
drsuneethadk@gmail.com |
| Dr Ashish Bhalla |
Post Graduate Institute of Medical Education & Research |
Department of Internal Medicine
Post Graduate Institute of Medical Education & Research
Sector 12
Chandigarh
CHANDIGARH |
9417023973
bhalla.chd@gmail.com |
| Dr Surendra Kumar |
S.P.Medical College & A. G. of Hospitals |
Research Room, Near Medicine ICU and Maharaja MRI, Department of Medicine,
Bikaner
RAJASTHAN |
9414604192
drsurendrakumar@rediffmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Ethics Committee, S. P. Medical College, Pawanpuri, Bikaner, Rajasthan - 334003 |
Approved |
| Father Muller Institutional Ethics Committee (FMIEC) Father Muller Research Centre Father Muller Road Kankanady Manguluru-575 002 Karnataka, India |
Approved |
| IEC Department of Pharmacology, Govt. Medical College, Nagpur |
Approved |
| IEC Intervention Studies JIPMER JIPMER, Dhanvantari Nagar, Puducherry - 605006 India |
Approved |
| Institutional Ethics Committee Calcutta National Medical College Calcutta National Medical College & Hospital, 32 Gorachand Road, Beniapukur, Kolkata, West Bengal- 700014, India |
Approved |
| Institutional Ethics Committee, Govt. Medical College, Room 1&2 Ground Floor, Lecture Theatre Complex Medical College Campus 673008 |
Approved |
| Institutional Ethics Committee, P N Chuttani, Block B 6th Floor, Post Graduate Institute of Medical Education & Research, Sector 12, Chandigarh - 160012, India |
Approved |
| Institutional Ethics Committee-Mysore Medical College and Research Institute and Associated Hospitals, Department of Pathology, K R Hospital , Mysore Medical College and Research Institute , Irwin Road,Mysuru-570001,Karnataka,India |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
| Status |
| No Objection Certificate |
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: T630||Toxic effect of snake venom, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Standard of Care (SOC) Antivenom Therapies |
Contains the excipients lactose monohydrate, microcrystalline cellulose, and magnesium stearate. |
| Intervention |
Varespladib-Methyl / Placebo |
Varespladib-Methyl:
Tablet: Varespladib-methyl (LY333013) formulated as an immediate-release, white film-coated oval tablet (250 mg).
Capsule: Varespladib-methyl (LY333013) formulated as an immediate-release capsule (50 mg).
Placebo:
Tablet: The oral placebo is supplied as a white film-coated oval tablet to match the LY333013 250 mg tablet for oral administration and contains a subset of the excipients: lactose monohydrate, microcrystalline cellulose, and magnesium stearate.
Capsule: Placebo is supplied as an immediate-release capsule to match the 50 mg IP, and contains the excipients lactose monohydrate, microcrystalline cellulose, and magnesium stearate. |
|
Inclusion Criteria
Modification(s)
|
| Age From |
5.00 Year(s) |
| Age To |
95.00 Year(s) |
| Gender |
Both |
| Details |
1. Is a male or female ≥ 5 years of age with venomous snakebite and a qualifying SSS inclusion score.
SSS inclusion categories are: local wound, pulmonary, cardiovascular, hematologic, and nervous system.
Hematologic score may be counted if available, but inclusion should not wait for laboratory results. GI or Renal categories will not count for inclusion.
A qualifying SSS inclusion score may be either:
2 points in any single SSS inclusion category AND at least 1 point in any other SSS inclusion category
OR
≥ 3 in any single SSS inclusion category
2. Index event (snakebite) must be symptomatic and must have occurred within 8 hours of eligibility assessment.
3. Is willing (or legally authorized representative is willing) to provide informed consent prior to initiation of any study procedures. |
|
| ExclusionCriteria |
| Details |
1. Has received antivenom treatment for envenoming prior to enrollment in this study.
2. Has an upper gastrointestinal (GI) bleed evidenced by hematemesis, “coffee-ground†emesis or nasogastric spirate, or hematochezia thought to originate from upper GI tract.
3. Has history of cerebrovascular accident or intracranial bleeding of any kind, acute coronary syndrome, myocardial infarction, or severe pulmonary hypertension.
4. Has known history of inherited bleeding or coagulation disorder.
5. 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 antiarrhythmic drugs within 14 days prior to treatment.
6. 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.
7. Has chronic kidney disease (defined as Stage 4 or receiving dialysis) or acute renal insufficiency with an eGFR < 60 mL/min (including patients receiving hemodialysis or hemofiltration).
8. Has a known allergy or significant adverse reaction to varespladib-methyl or related compounds.
9. Is considered by the Investigator to be unable to comply with protocol requirements due to geographic considerations, psychiatric disorders, or other compliance concerns.
10. 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. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Area under the curve (AUC) of the snakebite severity score (SSS) from Baseline (pre-dosing) to 6 hours after first dose |
6 hours after first dose |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
SSS(pre-dosing) and PGIC from Baseline to Day7 after 1dose
Coagulation abnormalities in patients with SSS hematology score of ≥2 at Baseline to Day7
Hemolysis markers in patients with gross hemolysis at Baseline to Day3
Levels of the myonecrosis marker,CK in patients with≥2x institutional reference range at Baseline toDay3
Total differential antivenom requirement, duration of ventilatory support, ICU stay, hospitalization through Day28 along with all cause mortality and PSFS total score
|
Day 28 |
|
Target Sample Size
Modification(s)
|
Total Sample Size="110"
Sample Size from India="72"
Final Enrollment numbers achieved (Total)= "96"
Final Enrollment numbers achieved (India)="62" |
|
Phase of Trial
|
Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
01/02/2022 |
| Date of Study Completion (India) |
13/12/2022 |
| Date of First Enrollment (Global) |
06/09/2021 |
| Date of Study Completion (Global) |
14/12/2022 |
|
Estimated Duration of Trial
|
Years="0"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
No Publication Details as of now |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
Modification(s)
|
A study is Randomized, Double-Blinded, Placebo-Controlled Add-On Therapy to Evaluate the Safety, Tolerability, and Efficacy of a Multi-Dose Regimen of Oral Varespladib Methyl in Subjects Bitten by Venomous Snakes (BRAVO study - Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite) |