Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202103718625048 Date of Approval: 03/03/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Unithiol Phase I
Official scientific title TRUE-1: Trial of Repurposed Unithiol for snakebite Envenoming Phase 1 (Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Kenyan Adults)
Brief summary describing the background and objectives of the trial Snakebite affects over 5 million people each year, and over 100,000 per year die as a result. The only available treatment is antivenom, which has many shortcomings including high cost, intravenous administration, and high risk of adverse events. One of the most harmful components of viper venom are zinc-dependent enzymes which damage blood vessels: causing bleeding and skin damage. Unithiol is a chelator which binds zinc and has been shown to inhibit viper venom in laboratory studies. Unithiol has been in use for many years for treating metal poisoning. As higher doses of unithiol are thought to be needed to treat snake envenoming, this trial aims to assess the safety of increasing doses. This phase I open label clinical trial will monitor for adverse events in healthy Kenyan volunteers. Groups of eight people will receive escalating doses until a maximum dose is reached, which is predicted to be an efficacious dose based on pre-clinical studies. Four groups will receive a single oral dose, two groups a single intravenous dose and two groups multiple oral doses. Detailed pharmacokinetic analysis will be undertaken, which is anticipated to inform the dosing regimen for future phase II and III clinical trials.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TRUE1
Disease(s) or condition(s) being studied Injury, Occupational Diseases, Poisoning
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/09/2021
Actual trial start date 02/02/2022
Anticipated date of last follow up 03/05/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 64
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL https://wellcomeopenresearch.org/articles/7-90
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Unithiol Dose esclation anticipated as 300mg oral, 900mg oral, 1,200mg oral, and 1,500mg oral capsules. Intravenous doses anticipated as 3mg/kg and 5mg/kg. Single dosing for six of the eight dosing groups. 48 hours of dosing for two of the eight dosing groups. Frequency and dose will be guided by emerging pharmacokinetic data. As above 8
Control Group None NA NA 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Capable of giving informed consent • Male or female • KHDSS resident • 18-64 years old (inclusive) • Body weight 50-120kg • In good health, as determined by the investigator following medical history, drug history, examination, vital signs, ECG and blood tests • Willing to be admitted to the in-patient facility for up to 5 days for dosing and intensive blood sampling • On effective contraception as defined by: Use of effective method of contraception for duration of study (women only). We will ask the female volunteers to come with their family planning records to verify. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository). • Prescribed a concomitant medication other than paracetamol or an appropriate contraceptive, which in the opinion of the Investigator warrants exclusion. • Any significant current or past history of cardiovascular, respiratory, renal or hepatic disease. • Subjects who have taken any non-prescribed herbal medication or mineral supplement in the preceding 7 days, which in the opinion of the Investigator warrants exclusion. • Subject with clinically significant abnormal vital signs at screening • Abnormal laboratory findings deemed significant by the Investigator • Subjects who are pregnant or lactating • Decline pre-trial screening, including HIV testing • HIV positive subjects will be excluded from the trial and, if not already receiving appropriate clinic follow-up, would be referred to a government clinic for ongoing care • Subjects with asthma (due to possible risk of exacerbation with allergic type skin reactions to unithiol) • Subjects that have donated blood within the past 3 months • Subjects who in the opinion of the investigator should not participate Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 64 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/01/2021 Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
KENYA MEDICAL RESEARCH INSTITUTE SCIENTIFIC AND ETHICS REVIEW UNIT P.O. BOX 54840 00200 OFF MBAGATHI ROAD, NAIROBI, KENYA HOUSE NUMBER 8, KEMRI HEADQUARTERS Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/02/2021 Liverpool School of Tropical Medicine Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA Liverpool L35QA United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety and tolerability assessed through active follow-up for any solicited and unsolicited adverse events. 6 months follow-up
Secondary Outcome Pharmacokinetic analysis to calculate plasma drug concentration area under the curve during the initial 24-hours, the maximal concentration (Cmax), time to maximum concentration (Tmax) and the half-life (t1/2). 24 hours
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI Wellcome Trust Research Programme KEMRI square, Off hospital Rd Kilifi 80108 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
The Wellcome Trust 215 Euston Rd, Bloomsbury, London NW1 2BE London NW12BE United Kingdom
Cures Within Reach 134 N LaSalle Street, 1130 Chicago, IL 60602 Chicago 60602 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Liverpool School of Tropical Medicine Pembroke Pl, Liverpool L3 5QA Liverpool L35QA United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
University of Liverpool Liverpool Bioanalytical Facility, GCP Laboratories, William Henry Duncan Building, 6 West Derby Street, University of Liverpool, L7 8TX Liverpool L78TX United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Michael Abouyannis mabouyannis@kemri-wellcome.org +254727048061 KEMRI Wellcome Trust Research Programme, Off hospital Road, Administration building, Office 214
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Academic clinician
Role Name Email Phone Street address
Principal Investigator Mainga Hamaluba mhamaluba@kemri-wellcome.org +254722205901 KEMRI Wellcome Trust Research Programme, Off hospital Road, Administration building, Office 214
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Academic clinician
Role Name Email Phone Street address
Public Enquiries Michael Abouyannis mabouyannis@kemri-wellcome.org +254727048061 KEMRI Wellcome Trust Research Programme, Off hospital Road, Administration building, Office 214
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Academic clinician
Role Name Email Phone Street address
Scientific Enquiries Michael Abouyannis mabouyannis@kemri-wellcome.org +254727048061 KEMRI Wellcome Trust Research Programme, Off hospital Road, Administration building, Office 214
City Postal code Country Position/Affiliation
Kilifi 80108 United Kingdom Academic clinician
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Results will be published in international peer-reviewed open-access journals and presented at national and/or international conferences. Anonymized data will be shared through online data repositories for non commercial purpose and made accessible upon approval from the principal investigator, sponsor and the institutional data governance committee. Informed Consent Form,Study Protocol Within 12 months of publication of the primary outcome of the study. Controlled access upon approval from PI and institutional data governance committee.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information