Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202607921693996 Date of Registration: 27/07/2026
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Post-Discharge malaria chemoprevention (PDMC) plus R21/Matrix-M™ vaccination
Official scientific title A Phase IIb open-label randomized trial to assess the immunogenicity and safety of the malaria vaccine R21/Matrix-M™ combined with post-discharge malaria chemoprevention (PDMC) with dihydroartemisinin-piperaquine (DHA-PPQ) in children 6-60 months of age at high risk for re-admission and death in Ghana.
Brief summary describing the background and objectives of the trial Children hospitalized with severe malaria or severe anemia in sub-Saharan Africa face a disproportionate share of post-discharge deaths, with the highest risk in the first 2 months after discharge, yet the standard post-discharge malaria chemoprevention (PDMC) regimen only protects for about 3 months, and the R21/Matrix-M malaria vaccine currently excludes exactly this highest-risk group (severely ill children admitted between 6 and 60 months). PDMCVac is designed to bridge both gaps by combining the two interventions, R21/Matrix-M vaccine co-administered with DHA-PPQ chemoprevention in children recovering from severe malaria or anemia, to extend protection across the vulnerable post-discharge window rather than relying on either intervention alone. The study aims to evaluate the immunogenicity and safety of R21/Matrix-M™ combined with PDMC (DHA-PPQ) in children aged 6 and 60 months hospitalized with severe anaemia or severe malaria in Ghana, and to establish anti-NANP IgG as a correlate of protection in this high-risk population.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PDMCVAC
Disease(s) or condition(s) being studied Haematological Disorders,Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/12/2026
Actual trial start date
Anticipated date of last follow up 31/12/2028
Actual Last follow-up date
Anticipated target sample size (number of participants) 150
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group R21Matrix vaccine and Dihydroartemisinin piperaquine DHAPPQ Group A: PDMC monthly (DHA-PPQ for 3 months) plus three primary monthly doses of R21/Matrix MTM (0.5 mL IM) on days 0, 28 and 56 (+/- 3 days) plus a Booster vaccine on Day 421 (+/- 14 days). Group A : on days 0, 28 and 56 (+/- 3 days) plus a Booster vaccine on Day 421 (+/- 14 days). R21/Matrix-MTM vaccine evaluation of safety and immunogenicity in children that had been admitted to hospital will help to provide valuable data for licensing extension and vaccine use as a global malaria control strategy to reduce the burden of malaria in endemic regions. R21/Matrix-M™ malaria vaccine, developed through collaboration between the Jenner Institute at Oxford University and the Serum Institute of India leveraging by Novavax’s saponin-based adjuvant technology, received support from the European and Developing Countries Clinical Trials Partnership (EDCTP), the Wellcome Trust, and the European Investment Bank (EIB). Dihydroartemisinin-piperaquine (DHA-PPQ) is a fixed-dose artemisinin-based combination therapy (ACT) consisting of dihydroartemisinin, a fast-acting artemisinin derivative, and piperaquine, a long-acting bisquinoline antimalarial. It is approved for medical use in Europe (since 2011) and is included on the WHO Model List of Essential Medicines. DHA-PPQ is licensed in Ghana as a recommended second-line treatment for uncomplicated Plasmodium falciparum malaria and has been evaluated for safety across all three major ecological zones in Ghana through post-licensure surveillance studies. 50
Control Group Dihydroartemisinin piperaquine Group B: DHA-PPQ cycle only (3-day course, weight-based) 3 months Dihydroartemisinin-piperaquine (DHA-PPQ) is a fixed-dose artemisinin-based combination therapy (ACT) consisting of dihydroartemisinin, a fast-acting artemisinin derivative, and piperaquine, a long-acting bisquinoline antimalarial. It is approved for medical use in Europe (since 2011) and is included on the WHO Model List of Essential Medicines. DHA-PPQ is licensed in Ghana as a recommended second-line treatment for uncomplicated Plasmodium falciparum malaria and has been evaluated for safety across all three major ecological zones in Ghana through post-licensure surveillance studies. 50 Active-Treatment of Control Group
Control Group R21Matrix vaccine Group C: Three primary monthly doses of R21/Matrix-M only (0.5 mL IM), (+/- 3 days) plus a Booster vaccine on Day 421 (+/- 14 days). Days 0, 28 and 56 (+/- 3 days) plus a Booster vaccine on Day 421 (+/- 14 days). R21/Matrix-MTM vaccine evaluation of safety and immunogenicity in children that had been admitted to hospital will help to provide valuable data for licensing extension and vaccine use as a global malaria control strategy to reduce the burden of malaria in endemic regions. R21/Matrix-M™ malaria vaccine, developed through collaboration between the Jenner Institute at Oxford University and the Serum Institute of India leveraging by Novavax’s saponin-based adjuvant technology, received support from the European and Developing Countries Clinical Trials Partnership (EDCTP), the Wellcome Trust, and the European Investment Bank (EIB). 50 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. for Group A and B: The child will be 6 – 60 months of age at the time of first vaccination, has been admitted to the children`s ward of Saint Francis Xavier Hospital (SFXH) with severe anaemia (haemoglobin level <7.0 g/dL) or with severe P. falciparum malaria (WHO criteria for severe disease) 2. for Group C: healthy children aged 6 – 60 months of age at the time of first vaccination and from the same community irrespective of their hb level. 3. Signed informed consent/thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child to join the trial. 4. The investigator believes that the parents/guardians can and will comply with the requirements of the protocol if the child is enrolled in the study. 5. The child is a permanent resident of the study area and likely to remain a resident for the duration of the trial. 1. The child has previously received a malaria vaccine. 2. The child has received an investigational drug or vaccine other than the study vaccines within 30 days preceding the first dose of study vaccine or planned use during the study period. 3. The child is currently participating in another malaria intervention trial or any other clinical intervention trial likely to affect data interpretation of this trial. 4. The child has a history of allergic disease or reactions likely to be exacerbated by any component of the malaria or control vaccine. 5. The child has a history of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunizations or the study drug DHA-PPQ. 6. The child has a family history of sudden death or of congenital prolongation of the QTc interval, or takes concomitant medication known to prolong QTc interval, or has a prolonged QTc interval >440 ms in the baseline ECG. 7. Pathological biochemistry results (renal and liver function) of more than Grade 1 according to DAIDS Toxicity Scale for the Groups A and B (no biochemistry required for Group C). 8. The child has major congenital defects. 9. The child has severe anaemia associated with clinical signs or symptoms of decompensation, or a haemoglobin of ≤ 5.0 g/dL with indication of blood transfusion. 10. The child has had a blood transfusion or any other blood product within three months of enrolment. 11. The child has been administered immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. 12. The child has severe malnutrition requiring hospital admission, taking into consideration weight-for-length/height and/or mid-upper arm circumference, presence of oedema (kwashiorkor) with or without severe wasting. 13. The child has a known severe acute or chronic disease, resulting in clinically significant pulmonary, cardiovascular and gastrointestinal Infant: 1 Month(s)-12 Month(s),Preschool Child: 2 Year-5 Year 6 Month(s) 5 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 14/08/2026 Ghana Health Service Ethics Review Comittee
Ethics Committee Address
Street address City Postal code Country
Adenta Pantang Accra MB 190 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary outcome Anti-NANP IgG GMT at Day 84 - the sole primary endpoint. It's tested two ways, hierarchically ordered: Superiority - Group A (R21/Matrix-M + DHA-PPQ) vs. Group B (DHA-PPQ alone), on anti-NANP IgG GMT at Day 84 (±3 days), as the correlate of protection. Non-inferiority - Group A vs. Group C (age-/sex-matched healthy vaccinated controls), same timepoint. Day 84
Secondary Outcome Immunogenicity (booster durability and response)- Anti-NANP IgG GMT in Groups A and C at Day 421 (pre-booster, ~12 months post-primary series) and Day 449 (28 days post-booster); booster response reported as GMT ratio (Day 449 ÷ Day 421)." Day 421 and Day 449
Secondary Outcome Safety - solicited local/systemic AEs, unsolicited AEs, SAEs, and SUSARs, monitored continuously from Day 0 (first dose) through Day 449 (28 days post-booster), across Groups A, B, and C Continuous surveillance from Day 0 to Day 449, with active assessments at each scheduled visit
Secondary Outcome Clinical outcomes - death, hospital readmission, clinical malaria, and severe anaemia, tracked from Day 0 (enrolment) to Day 449 (study end), across Groups A, B, and C. Cumulative incidence from Day 0 to Day 449 ascertained via continuous passive surveillance and confirmed at scheduled visits
Secondary Outcome Haemoglobin concentration (g/dL) at Day 0 (pre-intervention baseline), Day 84 (post-primary series), Day 421 (pre-booster, ~12 months post-primary series), and Day 449 (post-booster), across Groups A, B, and C. Day 0, Day 84, Day 421, Day 449
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
St Francis Xavier Hospital Assin Foso Cape Coast 43 Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
Pharmavax GIZ Dag-Hammarskjold-Weg 1-5 Frankfurt Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Kumasi Center for Collaborative Research in Tropical Medicine AK-312-1059 Kumasi Ghana Research Institution
COLLABORATORS
Name Street address City Postal code Country
Bernhard Nocht Institute for Tropical Medicine 20359 Hamburg Germany
Jenner Institute Laboratories Oxford OX3 7DQ London United Kingdom
University of Hamburg Christoph-Probst-Weg 1, D-20251 Hamburg Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Oumou Maiga maiga@kccr.de +233322060351 South End Asuogya Road
City Postal code Country Position/Affiliation
Kumasi Ghana Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Robin Kobbe robin.kobbe@bnitm.de 004904042818535 Bernhard-Nocht-Strasse 74 D-20359 Hamburg
City Postal code Country Position/Affiliation
Hamburg Germany Co Principal Investigator
Role Name Email Phone Street address
Public Enquiries Isaac Agyiri id.agyiri@kccr.de +233548168511 South-end Asuogya Road
City Postal code Country Position/Affiliation
Kumasi Ghana Study Coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes For each enrolled participant (Groups A, B, and C), individual-level data will be collected across the following domains: Demographic and baseline data: age, sex, site of enrolment, index diagnosis (severe malaria, severe anaemia, severe pneumonia, sepsis), date of admission, date of discharge Intervention data: study group assignment (A: R21/Matrix-M + DHA-PPQ; B: DHA-PPQ alone; C: healthy vaccinated controls), vaccine dose dates, DHA-PPQ dosing dates and adherence Immunogenicity data: anti-NANP IgG titers at Day 0, Day 84, Day 421, and Day 449 (Groups A and C) Haematological data: haemoglobin concentration (g/dL) at Day 0, Day 84, Day 421, and Day 449 (all groups) Safety data: solicited local and systemic adverse events, unsolicited adverse events, SAEs, and SUSARs, with onset date, severity grade, relatedness assessment, and outcome, recorded through Day 449 Clinical outcome data: death, hospital readmission, clinical malaria episodes, and severe anaemia episodes, with event dates, through Day 449 Household/care-seeking data (if linked to the household CRF sub-study): care-seeking pathway, delay interval, informal antimicrobial exposure Informed Consent Form,Statistical Analysis Plan,Study Protocol De-identified individual participant data will be made available beginning 12 months after publication of the primary study results, and will remain available for 5 years thereafter Requests for access to de-identified IPD will be considered from qualified researchers with a scientifically sound proposal, subject to approval by the KCCR/PADMME-PDMCVac Study Steering Committee and execution of a data access/use agreement. Requests should be directed to the corresponding author/study PI. Data will be shared for the purpose of individual participant data meta-analysis or secondary analyses consistent with the original informed consent obtained from participants' caregivers.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Immunogenicity (booster durability and response)- Anti-NANP IgG GMT in Groups A and C at Day 421 (pre-booster, ~12 months post-primary series) and Day 449 (28 days post-booster); booster response reported as GMT ratio (Day 449 ÷ Day 421).", Day 421 and Day 449
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Clinical outcomes - death, hospital readmission, clinical malaria, and severe anaemia, tracked from Day 0 through Day 449, across Groups A, B, and C., Day 0 through Day 449
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Clinical outcomes - death, hospital readmission, clinical malaria, and severe anaemia, tracked from Day 0 through Day 449, across Groups A, B, and C., Day 0 through Day 449 Secondary Outcome, Clinical outcomes - death, hospital readmission, clinical malaria, and severe anaemia, tracked from Day 0 - first dose through Day 449 - study end, across Groups A, B, and C., Continuous surveillance from Day 0 to Day 449, with active assessment at each scheduled visit
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Safety - solicited local/systemic AEs, unsolicited AEs, SAEs, and SUSARs, monitored continuously from Day 0 (enrolment/first dose) through Day 449 (28 days post-booster), across Groups A, B, and C, Day 0 through Day 449
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Safety - solicited local/systemic AEs, unsolicited AEs, SAEs, and SUSARs, monitored continuously from Day 0 (enrolment/first dose) through Day 449 (28 days post-booster), across Groups A, B, and C, Day 0 through Day 449 Secondary Outcome, Safety - solicited local/systemic AEs, unsolicited AEs, SAEs, and SUSARs, monitored continuously from Day 0 (enrolment/first dose) through Day 449 (28 days post-booster), across Groups A, B, and C, Continuous surveillance from Day 0 to Day 449, with active assessments at each scheduled visit
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Safety - solicited local/systemic AEs, unsolicited AEs, SAEs, and SUSARs, monitored continuously from Day 0 (enrolment/first dose) through Day 449 (28 days post-booster), across Groups A, B, and C, Continuous surveillance from Day 0 to Day 449, with active assessments at each scheduled visit Secondary Outcome, Safety - solicited local/systemic AEs, unsolicited AEs, SAEs, and SUSARs, monitored continuously from Day 0 (first dose) through Day 449 (28 days post-booster), across Groups A, B, and C, Continuous surveillance from Day 0 to Day 449, with active assessments at each scheduled visit
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Haemoglobin concentration (g/dL) at Day 0 (pre-intervention baseline), Day 84 (post-primary series), Day 421 (pre-booster, ~12 months post-primary series), and Day 449 (post-booster), across Groups A, B, and C, Day 0, Day 84, Day 421, Day 449
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Clinical outcomes - death, hospital readmission, clinical malaria, and severe anaemia, tracked from Day 0 (enrolment) to Day 449 (study end), across Groups A, B, and C., Cumulative incidence from Day 0 to Day 449 ascertained via continuous passive surveillance and confirmed at scheduled visits
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 20/07/2026 To clarify and revise as per reviewer recommendation Secondary Outcome, Haemoglobin concentration (g/dL) at Day 0 (pre-intervention baseline), Day 84 (post-primary series), Day 421 (pre-booster, ~12 months post-primary series), and Day 449 (post-booster), across Groups A, B, and C., Day 0, Day 84, Day 421, Day 449