Trial of Oral Community SVMP INhibitors for Snakebite

NCT07500233 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 25-033-310
• Study Type: interventional
• Target: 504
• Locations: 0 countries
• Sites: N/A

Brief Summary

Bites by venomous snakes can cause disability and can be life-threatening. We are doing research in adult patients to try and find medications that can be administered orally and can help to reduce disability and death due to snakebite. We do not know whether the drugs in this study work in humans and we aim to discover this. In Stage A, we will provide a new drug or placebo (inactive medication) in community locations, such as rural health clinics, in Brazil and Ghana. Neither the patient nor the clinical team will know which treatment option has been allocated. If a drug were to show signs of working as a treatment during Stage A, it will progress to Stage B. In Stage B, we will provide the drug or antivenom (the current approved treatment for snakebite) in a hospital setting. During Stage B, the patient and the clinician will know which treatment has been received. The purpose of Stage B is to discover whether the drug might hold promise as an alternative treatment to antivenom in the future. Participants will be monitored closely during Stage B and 'rescue antivenom' will be given if they become unwell. The medications being considered were developed for other health conditions, like cancer, so have been given to patients across the world before. The medications may prove effective at inhibiting the damaging effects of snake venom. Each of the trial drugs could be taken by mouth (oral) in community clinics and ambulances, much sooner than the current treatment for snakebite injuries (antivenom), which is only given within hospitals. They may have other advantages too, like reduced cost and less chance of side effects, including severe allergic reaction. Before a medication is included in the trial it will be reviewed and approved by a group of experts. Before a medication is included in Stage B of the trial it will be reviewed for whether it is safe and effective enough (from Stage A results) to be compared against antivenom. Stage A Participants will be recruited in the field when they attend a community clinic or ambulance. They will be randomly assigned to receive either a study drug or a placebo. When they arrive at hospital, all participants will receive standard of care antivenom. Participants will continue to take study medication (or matching placebo) for 24 hours, and have frequent blood samples collected during their treatment. Once 20 participants have received the drug and twenty have received the placebo, recruitment for this drug will cease. The difference in the improvement in blood clotting studies (how long it takes to clot) will be compared between the participants receiving the drug and the placebo. If the drug shows an improvement in the clotting studies, then it will proceed to Stage B. If the drug fails to improve the clotting studies, or if it is found to cause unsafe side effects, then it will be rejected from progressing to Stage B. Stage B Participants will be recruited upon arrival at the hospital site and randomly assigned to receive either a study drug shown to be effective in Stage A or standard-of-care antivenom. Study drugs will be administered for 24 hours, during which all participants will undergo frequent blood sampling. Recruitment for each study drug will stop once 48 participants have received the drug and 48 have received antivenom. The primary comparison will be the improvement in blood clotting parameters between the intervention and control groups. If the study drug is safe and achieves a similar improvement to antivenom - allowing for up to a three-hour delay in effect due to oral absorption compared with intravenous antivenom - it will be considered a promising alternative therapy. Following a planned 3-day stay in hospital, all participants from Stage A and B will be followed up at 2 and 6 weeks. These follow-up visits can be conducted by telephone, outpatient hospital visit, or home visit, depending on what is most suitable for that individual. The end of study visit will take place at the 6-week visit.

Conditions

Snakebite

Keywords

envenoming

Outcome Measures

Primary Outcomes (2)

• Mean time until lab INR is less than 50% of the baseline value (efficacy)

  The mean time until the lab INR is \<50% of the baseline value (or less than 1.4 if the baseline value is \<2.8) on two consecutive measurements per treatment arm. Time is measured starting from randomisation. Time is measured until the first of the two consecutive measurements being \<50% or \<1.4. Baseline INR sample is defined as blood collected day 0 post-consent and prior to treatment administration.

  From randomisation until end of admission

• Incidence (cumulative) of safety events (safety)

  Incidence (cumulative) of any AE, non-serious AE, SAE, SAR, SUSAR. Cumulative incidence is calculated as the number (%) of participants who experience at least one AE in the pre-specified groups.

  From informed consent until 42 days after randomisation

Study Arms (5)

Oral Placebo Stage A

PLACEBO COMPARATOR

Drug: Oral placebo capsules

Stage B IV Antivenom

ACTIVE COMPARATOR

Drug: Antivenom Snakes

Stage A & B Oral DMPS

EXPERIMENTAL

Drug: 2,3-dimercapto-1-propanesulfonic acid

Stage A & B Oral Marimastat

EXPERIMENTAL

Drug: marimastat

Stage B IV Marimastat

EXPERIMENTAL

Drug: marimastat

Interventions

2,3-dimercapto-1-propanesulfonic acid DRUG

Oral administration

Also known as: unithiol, DMPS

Stage A & B Oral DMPS

marimastat DRUG

oral administration

Stage A & B Oral Marimastat; Stage B IV Marimastat

Oral placebo capsules DRUG

Oral placebo

Oral Placebo Stage A

Antivenom Snakes DRUG

Standard of care IV antivenom recommended in country

Stage B IV Antivenom

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Snakebite in the preceding 12 hours (Stage A \& B)
• Aged ≥18-years (Stage A \& B)
• Residing in the Amazonas region of Brazil or the Upper West region of Ghana (Stage A \& B)
• Capable of giving informed consent (Stage A \& B)
• Are eligible for antivenom treatment according to local guidelines (Stage B only)

You may not qualify if:

• individual with severe envenoming (defined in the protocol) (Stage A \& B)
• concomitant anticoagulation (heparins, coumarin anticoagulants such as warfarin, or direct oral anticoagulants such as apixaban) (Stage A \& B)
• pregnant or breastfeeding (Stage A \& B)

Sponsors & Collaborators

• Liverpool School of Tropical Medicine: lead
• Coefficient Giving (Formerly Open Philanthropy): collaborator
• Kumasi Centre for Collaborative Research (KCCR): collaborator
• Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD): collaborator

MeSH Terms

Conditions

Snake Bites

Interventions

Unithiol; marimastat

Condition Hierarchy (Ancestors)

Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Dimercaprol; Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals

Central Study Contacts

TOCSINS Trial Management

CONTACT

tocsins@lstmed.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Stage A is double blinded, Stage B is open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2026
• First Posted: March 30, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03