Ivermectin Safety in Small Children (ISSC)

University of Oxford

Status and phase: Enrolling; Phase 2

Conditions: Scabies

Treatments: Drug: Oral ivermectin; Other: Placebo tablet; Drug: Permethrin Cream; Other: Placebo cream

Study type: Interventional

Funder types: Other

Identifiers

NCT04332068

PAR20001

Details and patient eligibility

About

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.

Full description

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 has been funded by the Wellcome Trust (grant reference number: 218524/Z/19/Z).

Enrollment: 399 estimated patients

Sex: All

Ages: 2 months to 5 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

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 study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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399 participants in 4 patient groups

Arm 1

Active Comparator group

Description:

Permethrin cream plus placebo tablets

Treatment:

Drug: Permethrin Cream

Other: Placebo tablet

Arm 2

Experimental group

Description:

Ivermectin (200 µg/kg) plus placebo cream

Treatment:

Other: Placebo cream

Drug: Oral ivermectin

Arm 3

Experimental group

Description:

Ivermectin (400 µg/kg) plus placebo cream

Treatment:

Other: Placebo cream

Drug: Oral ivermectin

Arm 4

Experimental group

Description:

Ivermectin (800 µg/kg) plus placebo cream (Kenya and The Gambia sites)

Treatment:

Other: Placebo cream

Drug: Oral ivermectin