Perennial Malaria Chemoprevention in the Malaria Vaccine Era

NCT ID: NCT07322068

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1290 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-09-30
• Study Completion Date: 2033-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

PMC-Placebo

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.

Group Type: PLACEBO_COMPARATOR

Dihydroartemisinin Piperaquine Placebo

Intervention Type: DRUG

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

Sulfadoxine pyrimethamine + Amodiaquine placebo

Intervention Type: DRUG

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

PMC-SPAQ

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.

Group Type: EXPERIMENTAL

Sulfadoxine pyrimethamine + Amodiaquine

Intervention Type: 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.

Dihydroartemisinin Piperaquine Placebo

Intervention Type: DRUG

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

PMC-DP

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.

Group Type: EXPERIMENTAL

Dihydroartemisinin Piperaquine

Intervention Type: 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.

Sulfadoxine pyrimethamine + Amodiaquine placebo

Intervention Type: DRUG

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

Interventions

Sulfadoxine pyrimethamine + Amodiaquine

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.

Intervention Type: DRUG

Dihydroartemisinin Piperaquine

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.

Intervention Type: DRUG

Dihydroartemisinin Piperaquine Placebo

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

Intervention Type: DRUG

Sulfadoxine pyrimethamine + Amodiaquine placebo

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

Intervention Type: DRUG

Other Intervention Names

SPAQ; DP; DP Placebo; SPAQ Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 10 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: collaborator

Infectious Diseases Research Collaboration, Uganda

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Prasanna Jagannathan

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Prasanna Jagannathan, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Masafu General Hospital

Busia District, , Uganda

Countries

Uganda

Other Identifiers

84540

Identifier Type: -

Identifier Source: org_study_id