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.: PACTR202107598843502 Date of Registration: 27/07/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A randomized, double-blind, placebo-controlled trial to assess the safety, pharmacokinetics, and efficacy of escalating doses of oral ivermectin in scabies infected children weighing 5 to less than 15 kilograms
Official scientific title A randomized, double-blind, placebo-controlled trial to assess the safety, pharmacokinetics, and efficacy of escalating doses of oral ivermectin in scabies infected children weighing 5 to less than 15 kilograms
Brief summary describing the background and objectives of the trial Scabies is a skin infestation caused by a mite called Sarcoptes scabiei. Scabies is characterised by a rash and severe itching, which is an allergic reaction to the eggs and feces the females deposit as they tunnel under the skin. Oral ivermectin is a very safe and beneficial drug which has been shown to be highly effective for the treatment of scabies and more than a dozen different neglected tropical diseases (NTDs), many of which are associated with important public health problems. Current label indications for ivermectin prevent use in small children weighing less than 15 kg, due to limited safety data in this group. Many of the NTD treatment options for small children rely on compounds that are less safe and/or efficacious compared to oral ivermectin. Our proposal will establish the safety and pharmacokinetics of escalating doses of ivermectin (200, 400, 800 µg/kg) to treat scabies infected children weighing 5 to less than 15 kg. The safety assessment will provide crucial evidence on the use of ivermectin for numerous diseases in children weighing 5 to less than 15 kg. The information from measuring drug concentrations in the patients will inform the optimal dosing of this drug in small children. Assessment of the efficacy of ivermectin, compared to permethrin cream, for the treatment of scabies in small children can provide an important alternative treatment for this widespread disease. This trial will evaluate the safety, pharmacokinetics, and efficacy of ivermectin in scabies infected children weighing 5 to less than 15kg. This will allow future efforts to expand the indication of ivermectin treatment to infants weighing 5 to less than 15kg to treat numerous NTDs, allowing this young age group equitable access to the numerous benefits of ivermectin therapy.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ISSC
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied skin infestation ,Scabies
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/02/2022
Actual trial start date 18/11/2023
Anticipated date of last follow up 30/04/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 399
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
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 Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Permethrin cream Permethrin cream plus placebo tablets Individual participant involvement will be 15 days. Permethrin cream is registered for the treatment of scabies in children 2months and older 108 Placebo
Experimental Group Ivermectin 3mg tablets Ivermectin (200 µg/kg) tablets plus placebo cream Individual participant involvement will be 15 days. Ivermectin is registered for treatment of several neglected tropical diseases (NTDs), including scabies, onchocerciasis, lymphatic filariasis, and strongyloidiasis. These diseases can afflict small children that could derive direct benefit by expanding use of ivermectin to children weighing less than 15kg. 108
Experimental Group Ivermectin 3mg tablets Ivermectin (400 µg/kg) tablets plus placebo cream Individual participant involvement will be 15 days. Ivermectin is registered for treatment of several neglected tropical diseases (NTDs), including scabies, onchocerciasis, lymphatic filariasis, and strongyloidiasis. These diseases can afflict small children that could derive direct benefit by expanding use of ivermectin to children weighing less than 15kg. 108
Experimental Group Ivermectin 3mg tablets Ivermectin (800 µg/kg) tablets plus placebo cream (Kenya and The Gambia sites) Individual participant involvement will be 15 days. Ivermectin is registered for treatment of several neglected tropical diseases (NTDs), including scabies, onchocerciasis, lymphatic filariasis, and strongyloidiasis. These diseases can afflict small children that could derive direct benefit by expanding use of ivermectin to children weighing less than 15kg. 75
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Male or female child weighing 5 to <15 kilograms • ≥2 months old • Scabies infestation • Available to attend all study visits • Parents/guardians/carers able to provide consent The participant may not enter the trial if ANY of the following apply: • A history of renal or hepatic impairment. • Any other significant disease or disorder (e.g. moderate or severe malnutrition) which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. • Participants who have participated in another research trial involving an investigational product in the past 12 weeks. • Children with Crusted/Norwegian scabies or severe secondary bacterial infections (e.g. sepsis) • Children who have taken ivermectin or topical permethrin cream within the last two weeks • Children with known allergies to ivermectin or topical permethrin cream or excipients • Loa loa infection risk, assessed based on travel history to endemic areas • Use of prescription (especially CYP3A4 inhibitors or inducers) or non-prescription drugs (except paracetamol at doses of up to 90 milligrams/kg/day), including vitamins (especially vitamin C), herbal and dietary supplements (including St. John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 times the drug half-life (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure, unless in the opinion of investigator, the medication will not interfere with the study procedures or compromise patient safety; the investigator will take advice from the manufacturer representative as necessary. • The investigator, health care provider or study staff feel that the patient is not suitable for study participation due to chronic illness, suspected underlying illness, or concerns that the patient will adhere to follow-up schedule. • Previously treated in the ISSC Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 2 Month(s) 60 Month(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 04/12/2020 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
University of Oxford Research Services, University Offices Wellington Square, Oxford OX1 2JD Oxford OX1 2JD United Kingdom
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 18/05/2021 Kenya Medical Research Institute
Ethics Committee Address
Street address City Postal code Country
KEM RI CGHR, PO1579-4010 Kisumu 1579-4010 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 13/05/2021 Fundacao Alfredo da Matta FUAM EC
Ethics Committee Address
Street address City Postal code Country
Rua Codajas n 24 Sala 14 1 Andar Bairro Cachoeirinha Manaus Amazonas Amazonas 69.065-13 Brazil
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 09/11/2021 Comissao Nacional de Etica em Pesquisa
Ethics Committee Address
Street address City Postal code Country
SRTV 701 Via W 5 Norte lote D Edificio PO 700 3 andar Asa Norte Brasilia DF Brazil Brasilia 70719-040 Brazil
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 15/05/2022 The Gambia Government Medical Research Council Joint Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Medical Research Council PO Box 273 Banjul 273 Gambia
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 14/02/2024 Kenya Pharmacy and Poisons Board
Ethics Committee Address
Street address City Postal code Country
LENANA ROAD Nairobi 27663-005 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Pruritus is the primary adverse event of concern that will be assessed from all treatment arms. Assessments will be performed at planned visits on days 0, 3, 7, 10, 14, and daily via diary cards.
Secondary Outcome Ivermectin and metabolite concentrations (e.g. Cmax, Tmax, area-under-the-curve). Days 0, 3, 7, 10, 14
Secondary Outcome Reduction in scabies burden Days 0, 7, 14
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Fundacao Alfredo da Matta FUAM Rua Codajas n 24 Sala 14 1 Andar Bairro Cachoeirinha Manaus Amazonas Amazonas Brazil
Kenya Medical Research Institute KEM RI CGHR, PO Box 1579-40100 Kisumu Kenya
Medical Research Council Unit The Gambia PO Box 273, Banjul The Gambia Banjul Gambia
FUNDING SOURCES
Name of source Street address City Postal code Country
Welcome Trust Gibbs Building 215 Euston Road London NW1 2BE London United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford University of Oxford University Offices Wellington Square Oxford OX1 2JD Oxford OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Lorenz von Seidlein Lorenz@tropmedres.ac +66023549170 420/6 Rajvithi road, Rajthevee
City Postal code Country Position/Affiliation
Bangkok 10400 Thailand Mahidol Oxford Tropical Medicine Research Unit
Role Name Email Phone Street address
Public Enquiries Lorenz von Seidlein Lorenz@tropmedres.ac +66023549170 420/6 Rajvithi road, Rajthevee
City Postal code Country Position/Affiliation
Bangkok 10400 Thailand Mahidol Oxford Tropical Medicine Research Unit
Role Name Email Phone Street address
Scientific Enquiries Lorenz von Seidlein Lorenz@tropmedres.ac +66023549170 420/6 Rajvithi road, Rajthevee
City Postal code Country Position/Affiliation
Bangkok 10400 Thailand Mahidol Oxford Tropical Medicine Research Unit
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes With participant’s consent, participant’s data and results from blood analyses stored in the database may be shared with other researchers to use in the future in a de-identified form according to the terms defined in the MORU data sharing policy. After publication other scientists not associated with the investigatory team can gain access to the study through a request to the MORU Data Access Committee. Study Protocol After completion of trial activities and reporting After publication other scientists not associated with the investigatory team can gain access to the study through a request to the MORU Data Access 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