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

NCT04978272 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: MIC-DroPU01AI155325
• Study Type: interventional
• Target: 924
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malaria

Keywords

dihydroartemisinin-piperaquine; intermittent preventive therapy; children; immune response

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Incidence of complicated malaria

  2 years to 4 years of age

• Incidence of hospital admissions and/or deaths

  2 years to 4 years of age

• Prevalence of parasitemia

  2 years to 4 years of age

• Prevalence of anemia

  2 years to 4 years of age

Study Arms (3)

IPTc DP 1 year

ACTIVE COMPARATOR

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); Other: DP Placebo

IPTc DP 2 years

ACTIVE COMPARATOR

DP given from 8 weeks to 104 weeks of age; No IPTc in third and fourth years of follow-up.

Drug: Dihydroartemisinin-piperaquine (DP)

No IPTc

PLACEBO COMPARATOR

DP placebo given from 8 weeks to 104 weeks of age; No IPTc in third and fourth years of follow-up.

Other: DP Placebo

Interventions

Dihydroartemisinin-piperaquine (DP) DRUG

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.

Also known as: Duo-Cotecxin

IPTc DP 1 year; IPTc DP 2 years

DP Placebo OTHER

Placebos will be identical appearance to DP.

IPTc DP 1 year; No IPTc

Eligibility Criteria

• Age: Up to 2 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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)
• Resident of Busia District
• Provision of informed consent by parent/guardian
• Agreement to present for any illness and avoid, where possible, medications outside the study protocol.

You may not qualify if:

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

Sponsors & Collaborators

• Grant Dorsey, M.D, Ph.D.: lead
• Stanford University: collaborator
• Karolinska Institutet: collaborator
• Infectious Diseases Research Collaboration, Uganda: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

IDRC - Tororo Research Clinic

Tororo, Uganda

Location

Related Publications (12)

• Dobbs KR, Jagannathan P, Dechavanne C. Editorial: Immune tolerance and human malaria. Front Immunol. 2024 Jul 4;15:1450480. doi: 10.3389/fimmu.2024.1450480. eCollection 2024. No abstract available.

  PMID: 39026667 BACKGROUND

• Nideffer J, Jagannathan P. Type I regulatory T cells in malaria: of mice and men. J Clin Invest. 2023 Jan 3;133(1):e166019. doi: 10.1172/JCI166019.

  PMID: 36594472 BACKGROUND

• Hughes E, Wallender E, Kajubi R, Jagannathan P, Ochieng T, Kakuru A, Kamya MR, Clark TD, Rosenthal PJ, Dorsey G, Aweeka F, Savic RM. Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women. Clin Infect Dis. 2022 Aug 31;75(3):406-415. doi: 10.1093/cid/ciab965.

  PMID: 34864925 BACKGROUND

• Li J, Wang X, Lackner AI, Narasimhan P, Li L, Mallajosyula V, Johnson MM, Hobler AL, Kirosingh AS, Braun AE, Nankya F, Musinguzi K, Kakuru A, Kamya M, Rosenthal PJ, Dorsey G, Jagannathan P, Angelo M, Pollheimer J, Gaw SL, Winn VD, Nadeau KC, Davis MM. Regulatory KIR+CD8+ T cells are elevated during human pregnancy. Sci Transl Med. 2025 Aug 6;17(810):eadm7697. doi: 10.1126/scitranslmed.adm7697. Epub 2025 Aug 6.

  PMID: 40768597 RESULT

• Roh ME, Gutman J, Murphy M, Hill J, Madanitsa M, Kakuru A, Barsosio HC, Kariuki S, Lusingu JPA, Mosha F, Kajubi R, Kamya MR, Mathanga D, Chinkhumba J, Laufer MK, Mlugu E, Kamuhabwa AAR, Aklillu E, Minzi O, Okoro RN, Geidam AD, Ohieku JD, Desai M, Jagannathan P, Dorsey G, Ter Kuile FO. Dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a systematic review and individual participant data meta-analysis. medRxiv [Preprint]. 2024 Nov 26:2024.11.23.24315401. doi: 10.1101/2024.11.23.24315401.

  PMID: 39649586 RESULT

• Tukwasibwe S, Lewis SN, Taremwa Y, van der Ploeg K, Press KD, Ty M, Namirimu Nankya F, Musinguzi K, Nansubuga E, Bach F, Chamai M, Okitwi M, Tumusiime G, Nakimuli A, Colucci F, Kamya MR, Nankabirwa JI, Arinaitwe E, Greenhouse B, Dorsey G, Rosenthal PJ, Ssewanyana I, Jagannathan P. Natural killer cell antibody-dependent cellular cytotoxicity to Plasmodium falciparum is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission. Clin Transl Immunology. 2024 Nov 1;13(11):e70005. doi: 10.1002/cti2.70005. eCollection 2024.

  PMID: 39493859 RESULT

• Tong Y, Ratnasiri K, Hanif S, Nguyen AT, Roh ME, Dorsey G, Kakuru A, Jagannathan P, Benjamin-Chung J. Intermittent preventive treatment for malaria in pregnancy and infant growth: a mediation analysis of a randomised trial. EBioMedicine. 2024 Nov;109:105397. doi: 10.1016/j.ebiom.2024.105397. Epub 2024 Oct 16.

  PMID: 39418986 RESULT

• Reyes RA, Turner L, Ssewanyana I, Jagannathan P, Feeney ME, Lavstsen T, Greenhouse B, Bol S, Bunnik EM. Differences in phenotype between long-lived memory B cells against Plasmodium falciparum merozoite antigens and variant surface antigens. PLoS Pathog. 2024 Oct 28;20(10):e1012661. doi: 10.1371/journal.ppat.1012661. eCollection 2024 Oct.

  PMID: 39466842 RESULT

• Nideffer J, Ty M, Donato M, John R, Kajubi R, Ji X, Nankya F, Musinguzi K, Press KD, Yang N, Camanag K, Greenhouse B, Kamya M, Feeney ME, Dorsey G, Utz PJ, Pulendran B, Khatri P, Jagannathan P. Clinical immunity to malaria involves epigenetic reprogramming of innate immune cells. PNAS Nexus. 2024 Aug 6;3(8):pgae325. doi: 10.1093/pnasnexus/pgae325. eCollection 2024 Aug.

  PMID: 39161730 RESULT

• Boyle MJ, Engwerda CR, Jagannathan P. The impact of Plasmodium-driven immunoregulatory networks on immunity to malaria. Nat Rev Immunol. 2024 Sep;24(9):637-653. doi: 10.1038/s41577-024-01041-5. Epub 2024 Jun 11.

  PMID: 38862638 RESULT

• Lee JJ, Kakuru A, Jacobson KB, Kamya MR, Kajubi R, Ranjit A, Gaw SL, Parsonnet J, Benjamin-Chung J, Dorsey G, Jagannathan P, Roh ME. Monthly Sulfadoxine-Pyrimethamine During Pregnancy Prevents Febrile Respiratory Illnesses: A Secondary Analysis of a Malaria Chemoprevention Trial in Uganda. Open Forum Infect Dis. 2024 Mar 13;11(4):ofae143. doi: 10.1093/ofid/ofae143. eCollection 2024 Apr.

  PMID: 38585183 RESULT

• Kakuru A, Jagannathan P. Can we reduce malaria in pregnancy and improve birth outcomes? Lancet. 2023 Mar 25;401(10381):973-975. doi: 10.1016/S0140-6736(23)00101-0. Epub 2023 Mar 10. No abstract available.

  PMID: 36913960 RESULT

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Prasanna Jagannathan, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Administration of all study drugs will be double blinded. All doses of study drugs will be prepackaged by a study pharmacist and administered by a study nurse blinded to the study participant's treatment regimen. All 3 daily doses will be directly observed in the clinic. If a study participant vomits the study drug within 30 minutes of administration, the drug will be re-administered. All doses of study drugs will be given between 8 and 104 weeks (2 years) of age.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Double blinded randomized controlled trial

Study Record Dates

• First Submitted: July 23, 2021
• First Posted: July 27, 2021
• Study Start: February 8, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)