The Impact RTS,S/AS01 Vaccine in School Aged Children RTS,S/AS01 Malaria Vaccine in School Aged Children

NCT06424002 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: P.09/22/3771
• Study Type: interventional
• Target: 5,400
• Locations: 0 countries
• Sites: N/A

Brief Summary

Across sub-Saharan Africa, school-age children bear an under-appreciated burden of malaria. An estimated 200 million school-age children are at risk of malaria and in many areas prevalence of infection exceeds 50%. The high infection rates in this group serves as a source of onward parasite transmission, undermining elimination and control efforts. Furthermore, malaria illness and malaria-induced anemia in this age group lead to school absenteeism, and impaired cognitive function and classroom attention, ultimately resulting in reduced academic achievement. Although universal malaria interventions, such as insecticide treated nets (ITNs) and access to prompt diagnosis and treatment are available to school-age children, this age group is the least likely to benefit from these interventions. Furthermore, efficacy of these approaches may be compromised by increasing anti-malarial drug and insecticide resistance. A malaria vaccine could help to avert the burden of malaria in this age group. The RTS,S/AS01 malaria vaccine has recently been recommended for vaccination of young children (\< 24 months) by the World health organization (WHO) after a Phase 3 trial and an implementation trial showed that the vaccine had moderate but significant efficacy to prevent clinical and severe malaria in young children. Previous randomized trials suggest that the vaccine is safe for older children. However, efficacy of the vaccine has never been assessed in school age children. Kamuzu University of Health Sciences in partnership with the Malawian Ministry of Health seeks to evaluate the efficacy of the newly introduced RTSS/AS01 malaria vaccine in school aged children. The study hypothesizes that vaccination will decrease the morbidity and transmission of malaria, as well as improve school absenteeism and educational outcomes.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (2)

• Proportion of enrolled school children with clinical malaria incident events throughout the study period (PCD).

  Based on symptoms of malaria plus a positive malaria rapid diagnostic test. A bood slide will also be collected for future assessment for malaria parasites

  During 18 months of follow up, when the child presents with symptoms of malaria within 48 hours at the leaner treatment kit (LTK) program which is run by teachers

• Proportion of enrolled school children that are daily absent from class throughout the study period (using electronic classroom registers)

  This will be based on electronic classroom registers

  During 18 months of follow up, a daily register will be administered to record school attendance

Secondary Outcomes (6)

• Proportion of enrolled school children who pass their examinations at the end of the year and proceed to the next class (Pupil's passing fraction based on classroom records)

  During 18 months of follow up, classroom records will record children passing end of year examinations

• Proportion of enrolled school children with clinical malaria incident events throughout the study period (ACD)

  During 18 months of follow up, clinical malaria will be assessed during sick visits (PCD) and during active case detection

• Proportion of enrolled school children with P. falciparum infections during the study period (ACD).

  During 18 months of follow up, malaria infection will be assessed during the ACD visits

• Proportion of children with low levels of hemoglobin levels (hb<11g/dl) during the study period (ACD).

  At baseline, midline, endline and during ACD visits, hemoglobin levels will be measured during the 18 months follow up period

• Proportion of siblings of enrolled children with P. falciparum infections at the beginning and end of the study period (indirect or "spill over" effect) (ACD)

  During 18 months of follow up, malaria infection will be assessed during the ACD visits

Study Arms (4)

RTS,S/AS01 Vaccine

EXPERIMENTAL

Three doses of the vaccine will be administered, each with one month interval. RTS,S is a subunit vaccine that includes a portion of the circumsporozoite protein (CSP) co-expressed with Hepatitis B surface antigen. The adjuvant is AS01.

Biological: Mosquirixs

RTS,S/AS01 Vaccine plus artemether-lumefantrine

EXPERIMENTAL

RTS,S/AS01 Vaccine will be provided with a therapeutic dose of artemether-lumefantrine (20 mg of artemether and 120 mg of lumefantrine). Artemether-lumefantrine will be given twice a day for 3 days based on the weight of the child as per treatment guidelines.

Biological: Mosquirixs; Drug: artemether-lumefantrine

Artemether-lumefantrine only

EXPERIMENTAL

A therapeutic dose of artemether-lumefantrine will be given twice a day for 3 days based on the weight of the child as per treatment guidelines.

Drug: artemether-lumefantrine

Vitamin A

NO INTERVENTION

This is the control group where Vitamin A will be given.

Interventions

Mosquirixs BIOLOGICAL

RTS,S is a subunit vaccine that includes a portion of the circumsporozoite protein (CSP) co-expressed with Hepatitis B surface antigen. The adjuvant is AS01. Three doses of the vaccine will be administered, each with one month interval.

RTS,S/AS01 Vaccine; RTS,S/AS01 Vaccine plus artemether-lumefantrine

artemether-lumefantrine DRUG

A therapeutic dose of artemether-lumefantrine (20 mg of artemether and 120 mg of lumefantrine) will be given twice a day for 3 days based on the weight of the child as per treatment guidelines.

Artemether-lumefantrine only; RTS,S/AS01 Vaccine plus artemether-lumefantrine

Eligibility Criteria

• Age: 6 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Pupils aged approximately 6 years to 15 years and enrolled in Standard 1 - 8 in the participating schools
• Planning to remain in the study area for 1 year
• Parental/guardian consent for child's participation and child assent if the child is 13 years of age or older

You may not qualify if:

• Pregnancy, defined based on menstrual history. Pupils who had their last menstrual period more than 6 weeks before enrollment will be excluded. This threshold was chosen considering that menstrual cycles are irregular in this age group
• Viral infections resulting in fever, chills, new loss of taste/smell and sore throat
• Known allergy or history of adverse reaction to antimalarial treatment or vaccines
• Chronic use of anti-malarial medication, azithromycin, or cotrimoxazole
• Enrollment in any other study
• Evidence of heart disease, HIV, or epilepsy
• Severe disability

Sponsors & Collaborators

• Kamuzu University of Health Sciences: lead
• Ministry of Health, Malawi: collaborator
• Boston University: collaborator
• Michigan State University: collaborator

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Don P Mathanga, PhD

  Kamuzu University of Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Don P Mathanga, PhD

CONTACT

+2651871911; dmathang@mac.kuhes.ac.mw

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: May 21, 2024
• Study Start: June 1, 2024
• Primary Completion: December 20, 2024
• Study Completion: December 30, 2024
• Last Updated: May 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: At the end of the study
• Access Criteria: Access will be based on requests and review of the request. As per NIH policy, data will be shared through approved links.