Mass Vaccine and Drug Administration, Bangladesh

NCT06068530 | Recruiting Phase 4 DMC

• 1 other identifier: MAL23002
• Study Type: interventional
• Target: 10,000
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open i.e. not blinded, cluster-randomised, controlled intervention study. The study will use a factorial design to estimate the protective effectiveness of mass drug administrations, mass vaccinations, combined mass vaccinations and drug administrations versus the current standard of care.

Conditions

Plasmodium Falciparum Malaria

Keywords

Plasmodium Falciparum Malaria; Malaria Vaccine; Malaria Drug Administrations

Outcome Measures

Primary Outcomes (3)

• Falciparum malaria incidence by study groups

  Falciparum malaria incidence will be determined by the number of clinical falciparum malaria cases confirmed by Rapid diagnostic test (RDT) or microscopy to determine the overall protective efficacy against clinical falciparum malaria among study groups. The investigators will look for the presence of axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy as a primary case definition of clinical falciparum malaria.

  Data will be collected for two years following baseline intervention (Month 0 to Month 24)

• Falciparum malaria prevalence by study groups

  Falciparum malaria prevalence will be determined by the number of positive falciparum confirmed by dried blood spots (DBS) polymerase chain reaction (PCR) malaria detection method during cross-sectional surveys to determine the overall protective efficacy against subclinical P. falciparum among study groups. * The investigators will collect dried blood spots to detect malaria during cross-sectional surveys from the healthy participants. * Those who have axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy will receive treatment according to national treatment guidelines.

  PCR for malaria detection from DBS will be collected at 6th month intervals until two years following baseline intervention (Month 0, Month 6, Month 12, Month 18 and Month 24)

• Overall percentage of falciparum malaria positivity by study groups

  The percentage of falciparum malaria positivity will be determined by the number of falciparum positives detected by PCR, RDT or microscopy to determine overall protective efficacy against clinical and subclinical falciparum malaria among study groups. Dried blood spots to detect malaria from by PCR will be collected at baseline and every six months until two years. Clinical malaria data detected by rapid diagnostic test or microscopy will be collected for two years following intervention. * The investigators will look for the presence of axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy as a primary case definition of clinical malaria. * The investigators will collect dried blood spots to detect malaria during cross-sectional surveys from the healthy participants.

  DBS: Month 0, Month 6, Month 12, Month 18 and Month 24 and Clinical malaria data for two year following intervention

Secondary Outcomes (17)

• The incidence of Deaths related to falciparum malaria among study groups

  Data will be collected for two years following baseline intervention (Month 0 to Month 24)

• The incidence of severe malaria disease among study groups

  Data will be collected for two years following baseline intervention (Month 0 to Month 24)

• The incidence of severe anaemia among study groups

  Data will be collected for two years following baseline intervention (Month 0 to Month 24)

• Vivax malaria incidence by study groups

  Data will be collected for two years following baseline intervention (Month 0 to Month 24)

• Vivax malaria prevalence by study groups

  PCR for malaria detection from DBS will be collected at 6th month intervals until two years following baseline intervention (Month 0, Month 6, Month 12, Month 18 and Month 24)

Study Arms (4)

MDA + Vaccine

ACTIVE COMPARATOR

The participants in MVDA villages will receive R21/Matrix M at M0, M1, M2, and a booster M12 plus DHA/piperaquine and a SLD-PQ at M0, M1, and M2

Drug: DHA/piperaquine and a SLD-PQ; Biological: Study vaccine R21/Matrix-M™

MDA only

ACTIVE COMPARATOR

The participants in MDA only villages will receive DHA/piperaquine and a SLD-PQ at M0, M1, and M2

Drug: DHA/piperaquine and a SLD-PQ

Vaccine only

ACTIVE COMPARATOR

The participants in vaccine only villages will receive R21/Matrix M at M0, M1, M2, and a booster M12

Biological: Study vaccine R21/Matrix-M™

Control

NO INTERVENTION

The participants in control will receive MVDA at the end of the 24th month assuming that MVDA is found to be safe and effective. During M0 to M24, the comparison villages will receive the standard of care as per national malaria treatment guidelines.

Interventions

DHA/piperaquine and a SLD-PQ DRUG

Participants in Arms 1 and 2 will receive three rounds of antimalarial drugs - each round starting on the day of vaccination (Day 0) at Study Months 0, 1, and 2. Each round consists of three daily doses of co-formulated dihydroartemisinin/piperaquine on Day 0, 1, and 2 (i.e. the day of vaccination and each day for 2 days after). The drug dose is based on the weight of the participant at the first visit (M0D0). Dihydroartemisinin/piperaquine tablets (Shanghai Fosun Pharmaceutical Co., Ltd.) for adult participants each contain 40 mg dihydroartemisinin and 320 mg piperaquine with a therapeutic dose range between 2-10 mg/kg/day dihydroartemisinin and 16-26 mg/kg/dose piperaquine. In addition, each participant will receive a single low dose primaquine on the day of vaccination (Day 0; Table 4). One single low dose primaquine of approximately 0.25 mg/kg (Thai Government Pharmaceutical Organisation) will be administered. Children under 10kg do not receive PQ.

MDA + Vaccine; MDA only

Study vaccine R21/Matrix-M™ BIOLOGICAL

The mixing prior to administration strategy will involve withdrawal of 0.5 mL antigen from one vial of R21 Malaria vaccine and adding it to Matrix-M1 vial. 0.5 mL of R21 antigen shall be withdrawn from another vial of R21 Malaria vaccine and be added to the same Matrix-M1 vial. The total volume in Matrix-M1 vial will be 1.5 mL. After addition the content will be mixed gently, and 0.75 mL of the mixture will be withdrawn and administered to participants. Each dose of 0.75mL (after mixing of R21 with Matrix-M1) will contain 10 µg of R21 and 50 µg for participants 14 years and older. In children up to 14 years a 5 μg will be used.

MDA + Vaccine; Vaccine only

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Current residence in a study village irrespective of permanence
• Age 6 months and above (no upper age limit)
• Written informed consent provided by participants (or a parent/guardian in case the participant is under 18 years old)

You may not qualify if:

• Pregnancy, plan to get pregnant, or breastfeeding.
• Acute illness requiring intervention
• A history of an adverse reaction to study drugs/vaccine and prior receipt of any other malaria vaccine or enrolment in another intervention trial.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (2)

Alikadam Upazila Health Complex

Bāndarban, 4650, Bangladesh

RECRUITING

Lama Upazila Health Complex

Lāma, 4641, Bangladesh

RECRUITING

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

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

Study Officials

• Lorenz von Seidlein

  Mahidol University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorenz von Seidlein

CONTACT

+66926486322; Lorenz@tropmedres.ac

Rupam Tripura

CONTACT

+8801572288558; Rupam@tropmedres.ac

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: August 22, 2023
• First Posted: October 5, 2023
• Study Start: February 15, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

BA (2)