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Ivermectin Safety in Small Children (ISSC)

Primary Purpose

Scabies

Status

Not yet recruiting

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Oral ivermectin

Permethrin Cream

Placebo tablet

Placebo cream

About this trial

This is an interventional treatment trial for Scabies focused on measuring Scabies, Ivermectin, permethrin

Eligibility Criteria

2 Months - 5 Years (Child)All SexesDoes not accept 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 month
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.
Not previously enrolled into this study

Sites / Locations

Chittagong Medical College
Alfredo da Matta Tropical Dermatology Foundation (FUAM)
MRC Unit The Gambia
Kenya Medical Research Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1

Arm 2

Arm 3

Arm 4

Arm Description

Permethrin cream plus placebo tablets

Ivermectin (200 µg/kg) plus placebo cream

Ivermectin (400 µg/kg) plus placebo cream

Ivermectin (800 µg/kg) plus placebo cream (except the Bangladesh site)

Outcomes

Primary Outcome Measures

Comparing the occurrence of adverse events between the intervention (ivermectin) and control (permethrin) groups

Pruritus will be assessed through physical examination and via diary cards provided to the parents/carers.

Secondary Outcome Measures

Population pharmacokinetic properties of ivermectin at escalating doses

Time to peak plasma concentration (Tmax; hours)

Population pharmacokinetic properties of ivermectin at escalating doses

Peak plasma concentration (Cmax; mg/L)

Population pharmacokinetic properties of ivermectin at escalating doses

Area under the plasma drug concentration-time curve (AUC0-24; mg×h×L-1)

Efficacy of oral ivermectin

Comparing the reduction of dermatological manifestations by "performing physical examination to quantify the number and size of scabies lesions on days 0, 7 and 14" in the oral intervention (oral ivermectin) and control (permethrin cream) groups.

Full Information

NCT ID

NCT04332068

First Posted

March 16, 2020

Last Updated

September 5, 2023

Sponsor

University of Oxford

Collaborators

Chittagong Medical College, Fundação Alfredo da Matta (FUAM), Kenya Medical Research Institute, Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), Medical Research Center Unit The Gambia (MRCG)

1. Study Identification

Unique Protocol Identification Number

NCT04332068

Brief Title

Ivermectin Safety in Small Children

Acronym

ISSC

Official Title

A Randomised, 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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 2023 (Anticipated)

Primary Completion Date

April 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Oxford

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Scabies

Keywords

Scabies, Ivermectin, permethrin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

The trial will initially randomize 30 participants at each site to receive control (permethrin cream), ivermectin 200 and 400 µg/kg (10:10:10) and review this data before escalation to ivermectin 800 µg/kg. Once the initial 30 participants have been treated a DSMB consultation will be performed for each site. If deemed safe to escalate to ivermectin 800 µg/kg, then remaining participants at each site will be treated with control (permethrin cream), ivermectin 200, 400, and 800 µg/kg (15: 15: 15: 25). The Bangladesh and Brazil sites will initially randomize 30 participants receive control (permethrin cream) and ivermectin 200 µg/kg (15:15) and review this data before escalation to ivermectin 400 µg/kg. Once the initial 30 participants have been treated a DSMB consultation will be performed. If deemed safe to escalate to ivermectin 400 µg/kg, then remaining participants at the Bangladesh site will be treated with control (permethrin cream), ivermectin 200, 400 µg/kg (18: 18: 33).

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

This is a double-blind trial so the participants, their parents, guardians or carers, administering clinicians, attending nurses, the central research team, and independent outcome assessors will all be blinded.

Allocation

Randomized

Enrollment

398 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Active Comparator

Arm Description

Permethrin cream plus placebo tablets

Arm Title

Arm 2

Arm Type

Experimental

Arm Description

Ivermectin (200 µg/kg) plus placebo cream

Arm Title

Arm 3

Arm Type

Experimental

Arm Description

Ivermectin (400 µg/kg) plus placebo cream

Arm Title

Arm 4

Arm Type

Experimental

Arm Description

Ivermectin (800 µg/kg) plus placebo cream (except the Bangladesh site)

Intervention Type

Drug

Intervention Name(s)

Oral ivermectin

Other Intervention Name(s)

NT007, Liconsa Laboratorios

Intervention Description

Ivermectin (NT007) 3 mg tablets are round, white, and scored on one side. Ivermentin 3mg tablets will be crushed and mixed thoroughly in 10mL of water.

Intervention Type

Drug

Intervention Name(s)

Permethrin Cream

Other Intervention Name(s)

Pioletal® Plus

Intervention Description

permethrin cream 5% (Pioletal® Plus) is a white coloured lotion with a homogenous appearance and an odour of fennel and lavender.

Intervention Type

Other

Intervention Name(s)

Placebo tablet

Intervention Description

placebo tablets are round, white, scored on one side. There are no active substances in the placebo tablets.

Intervention Type

Other

Intervention Name(s)

Placebo cream

Intervention Description

A placebo cream is a white coloured lotion with a homogenous appearance and an odour of fennel and lavender but lacking the permethrin agent.

Primary Outcome Measure Information:

Title

Comparing the occurrence of adverse events between the intervention (ivermectin) and control (permethrin) groups

Description

Pruritus will be assessed through physical examination and via diary cards provided to the parents/carers.

Time Frame

15 days

Secondary Outcome Measure Information:

Title

Population pharmacokinetic properties of ivermectin at escalating doses

Description

Time to peak plasma concentration (Tmax; hours)

Time Frame

15 days

Title

Population pharmacokinetic properties of ivermectin at escalating doses

Description

Peak plasma concentration (Cmax; mg/L)

Time Frame

15 days

Title

Population pharmacokinetic properties of ivermectin at escalating doses

Description

Area under the plasma drug concentration-time curve (AUC0-24; mg×h×L-1)

Time Frame

15 days

Title

Efficacy of oral ivermectin

Description

Time Frame

15 days

Other Pre-specified Outcome Measures:

Title

Pharmacogenomics of ivermectin

Description

Whole genome sequencing will be used to determine associations between pharmacogenetic variants with pharmacokinetic or pharmacodynamic parameters.

Time Frame

day 0

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Months

Maximum Age & Unit of Time

5 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 month 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. Not previously enrolled into this study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lorenz von Seidlein, Ass.Prof.

Phone

+66-(0)2-3549170

Lorenz@tropmedres.ac

First Name & Middle Initial & Last Name or Official Title & Degree

Kevin Kobylinski, phD

Phone

+66-(0)927298013

kobylinskikevin@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lorenz von Seidlein, Ass.Prof.

Organizational Affiliation

Mahidol Oxford Tropical Medicine Research Unit

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chittagong Medical College

City

Chittagong

Country

Bangladesh

Facility Name

Alfredo da Matta Tropical Dermatology Foundation (FUAM)

City

Manaus

Country

Brazil

Facility Name

MRC Unit The Gambia

City

Banjul

Country

Gambia

Facility Name

Kenya Medical Research Institute

City

Nairobi

Country

Kenya

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data collected for this study will be under the custodianship of MORU. With participant's consent, data from this study may be shared in a de-identified form with other groups or researchers in accordance with the MORU Data Sharing Policy.

IPD Sharing Time Frame

After completion of trial activities and reporting

IPD Sharing Access Criteria

MORU Data Sharing Policy. (http://www.tropmedres.ac/data-sharing-policy)

Learn more about this trial

Ivermectin Safety in Small Children

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