Perennial Malaria Chemoprevention in the Malaria Vaccine Era

NCT07322068 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 84540
• Study Type: interventional
• Target: 1,290
• Locations: 1 country
• Sites: 1

Brief Summary

Malaria remains a major cause of pediatric deaths and morbidity in Africa. An affordable malaria vaccine, R21, is being deployed in Uganda and other African countries with high malaria transmission, but efficacy is incomplete and wanes rapidly, and R21 does not provide protection until infants complete the primary vaccination series, or \~9 months of age. The goal of this study is to see whether combining R21 vaccination with two novel perennial malaria chemoprevention regimens can enhance protection against malaria compared with R21 alone. This study will take place at Masafu General Hospital (MGH) in Busia District, a rural area in Southeastern Uganda bordering Lake Victoria.

Conditions

Malaria, Falciparum

Outcome Measures

Primary Outcomes (1)

• Incidence of symptomatic malaria

  The incidence of symptomatic malaria is defined as the number of incident episodes of malaria requiring treatment per time at risk. Treatments within 14 days of a prior episode are not considered incident events.

  2.5 months to 60 months of age

Study Arms (3)

PMC-Placebo

PLACEBO COMPARATOR

Placebo given at Expanded Program of Immunization (EPI) visits (8 doses of placebo at 2.5, 3.5, 6, 7, 8, 9, 12, and 18 months of age). Participants will receive DP placebo plus SPAQ placebo. Placebos with an identical appearance to either DP or SPAQ active drugs will be provided by their manufacturers.

Drug: Dihydroartemisinin Piperaquine Placebo; Drug: Sulfadoxine pyrimethamine + Amodiaquine placebo

PMC-SPAQ

EXPERIMENTAL

Perennial malaria chemoprevention with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) given at Expanded Program of Immunization (EPI) visits (8 doses of SPAQ at 2.5, 3.5, 6, 7, 8, 9, 12, and 18 months of age). Participants will also receive DP placebo along with active SPAQ. Placebo with an identical appearance to DP active drug will be provided by its manufacturer.

Drug: Sulfadoxine pyrimethamine + Amodiaquine; Drug: Dihydroartemisinin Piperaquine Placebo

PMC-DP

EXPERIMENTAL

Perennial malaria chemoprevention with dihydroartemisinin-piperaquine (DP) given at Expanded Program of Immunization (EPI) visits (8 doses of DP at 2.5, 3.5, 6, 7, 8, 9, 12, and 18 months of age). Participants will also receive SPAQ placebo along with active DP. Placebo with an identical appearance to SPAQ active drug will be provided by its manufacturer.

Drug: Dihydroartemisinin Piperaquine; Drug: Sulfadoxine pyrimethamine + Amodiaquine placebo

Interventions

Sulfadoxine pyrimethamine + Amodiaquine DRUG

Each round of study drugs will consist of once daily oral dosing x 3 days. The first daily dose will be directly observed in the study clinic, and day 2 and day 3 doses will be provided for administration at home. Daily dosing of SPAQ will be based on manufacturer's recommendations: infants \<12 months of age will receive one dose of 12.5/250 mg SP and 3 daily doses of 76.5 mg AQ, children \>=12 months of age will receive one does of 25/5000 mg SP and 3 daily doses of 153 mg AQ.

Also known as: SPAQ

PMC-SPAQ

Dihydroartemisinin Piperaquine DRUG

Each round of study drugs will consist of once daily oral dosing x 3 days. The first daily dose will be directly observed in the study clinic, and day 2 and day 3 doses will be provided for administration at home. Daily dosing of DP will consist of half-strength tablets given once a day for 3 consecutive days and will depend on bodyweight, targeting 4 mg/kg of dihydroartemisinin and 24 mg/kg of piperaquine phosphate.

Also known as: DP

PMC-DP

Dihydroartemisinin Piperaquine Placebo DRUG

Participants receive oral placebos with an identical appearance to DP active drug.

Also known as: DP Placebo

PMC-Placebo; PMC-SPAQ

Sulfadoxine pyrimethamine + Amodiaquine placebo DRUG

Participants receive oral placebos with an identical appearance to SPAQ active drug.

Also known as: SPAQ Placebo

PMC-DP; PMC-Placebo

Eligibility Criteria

• Age: 1 Day - 10 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Residency in Busia District, Uganda
• Provision of informed consent by the parent/guardian for her child
• Agreement to come to the study clinic for any febrile episode or other illness and avoid, where possible, medications given outside the study protocol

You may not qualify if:

• Intention of permanently moving outside Busia district during the study period
• Active medical problem requiring inpatient evaluation or chronic medical condition requiring frequent medical attention at the time of screening
• Evidence of sickle cell disease (Hemoglobin SS genotype)
• Biological mother known to be HIV positive

Sponsors & Collaborators

• Stanford University: lead
• University of California, San Francisco: collaborator
• Infectious Diseases Research Collaboration, Uganda: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Masafu General Hospital

Busia District, Uganda

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

fanasil, pyrimethamine drug combination; Amodiaquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Prasanna Jagannathan, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 7, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): June 1, 2033
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: All scientific data generated from this project will be made available as soon as possible, and no later than the time of publication or the end of the funding period, whichever comes first.

Locations

UG (1)