Perennial Malaria Chemoprevention in the Malaria Vaccine Era

Phase 4Not Yet RecruitingNCT07322068

Stanford University1,290 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,290

Conditions

Malaria, Falciparum

Interventions

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.

Dihydroartemisinin PiperaquineDRUG

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.

Eligibility

Sex: ALLMin age: 1 DayMax age: 10 WeeksHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Outcomes

Primary Outcomes

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.

Time frame: 2.5 months to 60 months of age