Modifying Immunity in Children With DihydROartemisinin-Piperaquine (MIC-DroP) (MIC-DroP)

Enhancing Immunity to Malaria in Young Children With Effective Chemoprevention

The MIC-DroP trial will test the hypothesis that preventing early life blood-stage malaria antigenic exposure with intermittent preventive therapy (IPT) enhances protective immunity to malaria. This study will take advantage of a unique opportunity to study infants born to mothers followed in a NIH-funded randomized controlled trial of novel intermittent preventive therapy in pregnancy (IPTp) regimens (NCT04336189). MIC-DroP will leverage the parent IPTp study to enroll 924 children who will be randomized at 8 weeks of age to receive no intermittent preventive therapy in childhood (IPTc), monthly DP from 8 weeks to 1 year of age, or monthly DP from 8 weeks to 2 years of age, and then follow children to 4 years of age. The primary outcome of this study will be to compare the incidence of malaria from 2 to 4 years of age among children randomized to receive no IPTc, monthly DP for the first year of life, or monthly DP for the first two years of life. Investigators will also leverage this trial to evaluate immune development during early childhood.

Study Overview

• Status: Active, not recruiting
• Conditions: Malaria
• Intervention / Treatment: Drug: Dihydroartemisinin-piperaquine (DP); Other: DP Placebo

Detailed Description

This study is a phase III, double-blind, randomized controlled trial of 924 HIV- uninfected children. Children born to mothers enrolled in an ongoing clinical trial of different IPTp arms in pregnancy (NCT 04336189) will be enrolled in this study. In the parent IPTp study, 2757 HIV-uninfected pregnant women will be randomized to receive IPTp with monthly sulfadoxine pyrimethamine (SP) alone, monthly DP alone, or both monthly SP+DP, and followed through 4 weeks postpartum. At the 4-week postpartum visit, we will enroll and randomize 924 eligible children to one of three IPTc arms: no IPTc (the current standard of care), monthly DP from 8 weeks to 1 year of age, or monthly DP from 8 weeks to 2 years of age. Study drugs will be placebo controlled and all doses of study drug will be given by directly observed therapy (DOT). The intervention phase will be completed at 2 years of age, and children followed through 4 years of age. Study participants will be followed for all of their outpatient medical care in our dedicated study clinic. Malaria incidence will be measured via active case detection. Routine assessments will be performed in the study clinic for all study participants every 4 weeks, including passive surveillance for parasitemia by quantitive polymerase chain reaction (qPCR). Venous blood will be collected for immunologic assays three times annually from 8 weeks to 4 years of age. All maternal assessments conducted during the parent IPTp study, including assessment for maternal malaria exposure (e.g., placental histology) household survey, will be available and linked to each study participant.

• Study Type: Interventional
• Enrollment (Actual): 924
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Grant Dorsey, MD, PhD; Phone Number: 628-206-4680; Email: grant.dorsey@ucsf.edu

Study Locations

• Uganda
  • Tororo, Uganda
    • IDRC - Tororo Research Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 months (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Born to HIV-uninfected mother enrolled in parent clinical trial of intermittent preventative treatment of malaria in pregnancy (IPTp-SP vs. IPTp-DP vs. IPTp-SP+DP, NCT 04336189)
2. Resident of Busia District
3. Provision of informed consent by parent/guardian
4. Agreement to present for any illness and avoid, where possible, medications outside the study protocol.

Exclusion Criteria:

1. Intention of moving outside Busia district during the study period
2. Active medical problem requiring in-patient evaluation or chronic medical condition requiring frequent medical attention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IPTc DP 1 year; DP given from 8 weeks to 52 weeks of age; DP placebo given from 52 weeks to 104 weeks of age; No IPTc in third and fourth years of follow-up.	Drug: Dihydroartemisinin-piperaquine (DP); Duo-Cotecxin 20mg/160mg tabs by Holley-Cotec, Beijing, China Each treatment with DP will consist of half-strength tablets given once a day for 3 consecutive days according to weight-based guidelines.; Other Names: Duo-Cotecxin; Other: DP Placebo; Placebos will be identical appearance to DP.
Active Comparator: IPTc DP 2 years; DP given from 8 weeks to 104 weeks of age; No IPTc in third and fourth years of follow-up.	Drug: Dihydroartemisinin-piperaquine (DP); Duo-Cotecxin 20mg/160mg tabs by Holley-Cotec, Beijing, China Each treatment with DP will consist of half-strength tablets given once a day for 3 consecutive days according to weight-based guidelines.; Other Names: Duo-Cotecxin
Placebo Comparator: No IPTc; DP placebo given from 8 weeks to 104 weeks of age; No IPTc in third and fourth years of follow-up.	Other: DP Placebo; Placebos will be identical appearance to DP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of symptomatic malaria following cessation of IPTc	The incidence of symptomatic malaria, defined as the number of incident episodes of malaria requiring treatment per time at risk, during the period after the intervention was given (2-4 years of age). Treatments within 14 days of a prior episode are not considered incident events.	2 years to 4 years of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of complicated malaria	Any incident episode of malaria meeting World Health Organization criteria for severe malaria or danger signs per time at risk, during the period after the intervention was given (2-4 years of age).	2 years to 4 years of age
Incidence of hospital admissions and/or deaths	Admission to the pediatric ward for any cause, and deaths of any cause	2 years to 4 years of age
Prevalence of parasitemia	Proportion of routine visits with asexual parasites detected by blood smears or quantitative polymerase chain reaction (qPCR).	2 years to 4 years of age
Prevalence of anemia	Proportion of routine hemoglobin measurements <11 grams/dL	2 years to 4 years of age

Collaborators and Investigators

• Sponsor: Grant Dorsey, M.D, Ph.D.
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Karolinska Institutet; Stanford University; Infectious Diseases Research Collaboration, Uganda
• Investigators: Principal Investigator: Prasanna Jagannathan, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: July 23, 2021
• First Posted (Actual): July 27, 2021

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: children; immune response; dihydroartemisinin-piperaquine; intermittent preventive therapy
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Piperaquine; Artenimol
• Other Study ID Numbers: MIC-DroP; U01AI155325 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No