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| ID | Type | Description | Link |
|---|---|---|---|
| MR/T006161/1 | Other Grant/Funding Number | Medical Research Council [MRC] |
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Malaria remains one of the leading causes of morbidity and mortality worldwide. Plasmodium falciparum is a complex pathogen with numerous immune evasion mechanisms which has added layers of complexity to the development of safe and protective vaccines. There remains an urgent need to identify and develop more protective and more affordable vaccine candidates that could achieve the World Health Organization (WHO) goal of 75% efficacy against clinical malaria.
R21 is a novel pre-erythrocytic candidate malaria vaccine. R21 includes Hepatitis B surface antigen (HBsAg) fused to the C-terminus and central repeats of the circumsporozoite protein of P. falciparum (CSP), which self-assemble into virus-like particles in yeast. R21 lacks the excess HBsAg found and comprises only fusion protein moieties.
R21/MatrixM (MM) had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the serious adverse events were attributed to the vaccine. At one year, vaccine efficacy remained high, at 77%. Participants vaccinated with R21/MM showed high titres of malaria-specific anti- Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the primary series of vaccinations after a fourth dose administered one year later.
Currently, there are no safety and immunogenicity data for the use of R21/MatrixM in Asian populations. This trial will generate the required data for the use of this vaccine in Asia. For integration with the current targeted malaria elimination (TME) activities, which provide mass drug administrations at months M0, M1, and M2, it would be most efficient and practical to provide the vaccine at the same intervals.
In summary: The investigators propose to conduct a safety and immunogenicity trial of R21/MatrixM in Thai adults. The major aims of this study are to 1) assess the safety and immunogenicity of R21/MatrixM in Thai adults 2) confirm that the co-administration of antimalarial drugs with the malaria vaccine R21/MatrixM does not reduce the immunogenicity of the vaccine and 3) assess the absorption and pharmacokinetics of antimalarial drugs piperaquine, and a single low dose of primaquine (SLDPQ) when co-administered with R21/MatrixM.
This is a randomized, open label, single centre, Phase 2 study. 120 healthy non-pregnant Thai adults, aged 18-55 years, inclusive, will be recruited.
Each participant will be randomized into one of the following study arms in a ratio of 5:5:2, as follows:
This is a randomized, open label, single centre, Phase 2 study.
Screening and eligibility assessment (Screening visit) All potential volunteers will have a screening visit, which may take place up to 7 days prior to enrolment. Once informed consent is given, a screening number will be assigned in sequential order. Screening numbers will be issued consecutively (e.g. R21-001, R21-002, R21-003, …)
Enrolment, baseline assessment, regimen allocation, and first vaccination (Month 0 / Day 0 visit; Baseline visit) All inclusion and exclusion criteria will be checked before enrolment in the study. Physical examination will be performed. Any new medical issues or symptoms that have arisen will be assessed. Blood will be collected for baseline P. falciparum testing, haemoglobin and biochemistry. Participants with parasitaemia or anaemia will be treated according to national guidelines. Blood will be collected and stored for measurement of antibodies against P. falciparum circumsporozoite (anti-circumsporozoite antibody) until shipment to the reference laboratory. Urine will be collected from women of child-bearing age for immediate pregnancy test.
Enrolment, baseline assessment, regimen allocation, and first vaccination (Month 0 / Day 0 visit; Baseline visit)
All inclusion and exclusion criteria will be checked before enrolment in the study. Physical examination will be performed. Any new medical issues or symptoms that have arisen will be assessed. Blood will be collected for baseline P. falciparum testing, haemoglobin and biochemistry. Blood will be collected and stored for measurement of antibodies against P. falciparum circumsporozoite (anti-circumsporozoite antibody) until shipment to the reference laboratory. Urine will be collected from women of child-bearing age for immediate pregnancy test.
If all inclusion criteria are fulfilled and none of the exclusion criteria apply, the patient will be enrolled into the study and a case record form (CRF) specific to each participant completed. Regimen allocation and administration of the vaccine(s) will be on Day 0. The randomization lists will be prepared by Mahidol-Oxford Tropical Medicine Research Unit (MORU).
Randomization numbers will be generated in blocks, for the 3 study arms in a ratio of 5:5:2, as follows:
Study participants will be assigned the next available randomization number on the list, and thus will be randomly allocated to Group 1, 2, or 3. This is an open-label study. Participants and clinical investigators will not be blinded to group allocation.
Subjects (in group 1 and 2) will then be vaccinated by intramuscular (IM) needle injection into the deltoid region of the arm. Subjects in Groups 1 and 3 will also receive anti-malarial medications.
The study participants will be observed closely for at least 30 minutes following the administration of each study vaccine, with appropriate medical treatment readily available in case of an anaphylactic reaction.
Subsequent vaccination visits (Month 1 / Day 0 and Month 2 / Day 0 visits)
Physical examination will be performed. Any new medical issues or symptoms that have arisen will be assessed. Blood will be collected for P. falciparum testing. Participants with parasitaemia or anaemia will be treated according to national guidelines. Blood will be collected and stored for measurement of antibodies against P. falciparum circumsporozoite (anti-circumsporozoite) until shipment to the reference laboratory. Urine will be collected from women of child-bearing age for immediate pregnancy test.
Before vaccination, the on-going eligibility of the volunteer will be reviewed. All participants will attend the clinic for vaccination visits, will be observed closely for at least 30 minutes following the administration of each study vaccine.
Follow up assessments
Follow-up assessments (visits not involving vaccination) will be done at month 3 and month 6 after the first vaccination.
Blood tests
Blood will be drawn at the time points indicated in the schedule of procedures and the following laboratory assays performed:
At screening:
At M0, D0: P. falciparum testing, Haematology: Hb, WBC, PLT, Biochemistry: ALT, AST, CREA, anti-circumsporozoite antibody; Pharmacokinetics (piperaquine and primaquine drug levels will be assessed if additional data are required) At M0, D1: Pharmacokinetics (piperaquine and primaquine drug levels) At M0, D2: Pharmacokinetics (piperaquine drug levels) At M0, D7: Haematology: Hb, WBC, PLT; Biochemistry: ALT, AST, CREA; Pharmacokinetics (piperaquine drug levels) At M1, D0: P. falciparum testing, anti-circumsporozoite antibody; Pharmacokinetics (piperaquine drug levels) At M1, D1: Pharmacokinetics (piperaquine and primaquine drug levels) At M1, D2: Pharmacokinetics (piperaquine drug levels) At M1, D7: Haematology: Hb, WBC, PLT; Biochemistry: ALT, AST, CREA; Pharmacokinetics (piperaquine drug levels) At M2, D0: P. falciparum testing, anti-circumsporozoite antibody; Pharmacokinetics (piperaquine drug levels) At M2, D1: Pharmacokinetics (piperaquine and primaquine drug levels) At M2, D2: Pharmacokinetics (piperaquine drug levels) At M2, D7: Haematology: Hb, WBC, PLT; Biochemistry: ALT, AST, CREA; Pharmacokinetics (piperaquine drug levels) At M3: P. falciparum testing, Haematology: Hb, WBC, PLT; Biochemistry: ALT, AST, CREA; anti-circumsporozoite antibody At M6: P. falciparum testing, anti-circumsporozoite antibody
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| R21/Matrix-M + DHA-PIP+PQ | Experimental | The R21/Matrix-M vaccine (IM injection) + co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine |
|
| R21/Matrix-M only | Experimental | The R21/Matrix-M vaccine (IM injection) only |
|
| DHA-PIP+PQ only | Active Comparator | Co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| R21/Matrix-M vaccination | Biological | R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2. |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Unsolicited Adverse Events (AEs), According to the Medical Dictionary for Regulatory Activities (MedRA) Classification. | From the date of the first vaccination to 28 days after the last vaccination (up to approximately 1 month) | |
| Occurrence of Serious Adverse Events (SAEs), According to the MedRA Classification. | During the whole study period, i.e. during a 6-month follow-up period from the receipt of first vaccination | |
| Occurrence of Solicited Adverse Event Within 7 Days of Each Vaccination | Within 7 days of each vaccination. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Seroconversions in C-Term | Number of Participants with Seroconversions in C-Term | at study Month 1 |
| Number of Participants With Seroconversions in C-Term | Number of Participants with Seroconversions in C-Term |
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Inclusion Criteria
The participant is eligible to enter the study if all of the following apply:
Exclusion criteria
The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study:
Pregnancy or breastfeeding, or planned pregnancy during the course of the study.
Presence of any medical condition (physical or mental) which, may place the participant at undue risk or interfere with the results of the study*. Including: serious cardiac, renal, hepatic or neurological disease, severe malnutrition
Any confirmed or suspected immunosuppressive or immunodeficient condition. Including: history of splenectomy, human immunodeficiency virus (HIV) infection
Chronic administration (>14 days in total) of immunosuppressants or other immune-modifying drugs within six months of enrollment. Including: oral corticosteroids equivalent to prednisone > 20 mg/day (a)
History of an autoimmune disease
Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody(b) detected in serum.
Screening electrocardiogram (ECG) demonstrating a QTc interval ≥ 450 ms
Seropositivity for hepatitis C virus (antibodies to HCV) at screening (b)
Finding on safety laboratory values as defined below:
Abnormalities of examination or investigations at screening. Including: hepatomegaly, right upper quadrant abdominal pain or tenderness, abnormal blood tests (as defined in the protocol which are not listed above)
Positive malaria parasitaemia (RDT) at screening or baseline (Month 0, Day 0).
Receipt or planned receipt of an investigational medical product or participation in an interventional clinical trial during the study period
Contraindications to the use of artemisinins, piperaquine or primaquine*. Including: use of medications with known potential interactions, prior allergic reactions to one or more components of the drug regimen.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. egg products)
History of clinically significant contact dermatitis.
Contraindication to intramuscular (IM) injection*
Administration of a vaccine not included in the study protocol within 30 days of a study vaccine (c).
History of anaphylaxis post-vaccination.
Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.
Exceptions:
a Inhaled and topical steroids. b Participation in hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study c The following vaccinations may be administered more than 7 days before or after a study vaccination: polio, diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, Bacillus Calmette-Guérin (BCG vaccine), measles, influenza, pneumococcal disease, COVID-19 or yellow fever
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| Name | Affiliation | Role |
|---|---|---|
| Lorenz von Seidlein, MD | Mahidol Oxford Tropical Medicine Research Unit | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University | Bangkok | 10400 | Thailand |
All personal details of participants will be de-identified. These data including laboratory investigation results will be stored and may be shared with other researchers to apply in their research in accordance with the MORU data sharing policy.
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After completion of trial activities and reporting
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| ID | Title | Description |
|---|---|---|
| FG000 | R21/Matrix-M + DHA-PIP+PQ | The R21/Matrix-M vaccine (IM injection) + co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine R21/Matrix-M vaccination: R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2. DHA-PIP: Dihydroartemisinin/piperaquine tablets for adult patients 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. Participants 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. PQ: Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered. |
| FG001 | R21/Matrix-M Only | The R21/Matrix-M vaccine (IM injection) only R21/Matrix-M vaccination: R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2. |
| FG002 | DHA-PIP+PQ Only | Co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine DHA-PIP: Dihydroartemisinin/piperaquine tablets for adult patients 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. Participants 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. PQ: Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | R21/Matrix-M + DHA-PIP+PQ | The R21/Matrix-M vaccine (IM injection) + co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine R21/Matrix-M vaccination: R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2. DHA-PIP: Dihydroartemisinin/piperaquine tablets for adult patients 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. Participants 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. PQ: Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Occurrence of Unsolicited Adverse Events (AEs), According to the Medical Dictionary for Regulatory Activities (MedRA) Classification. | Posted | Count of Participants | Participants | From the date of the first vaccination to 28 days after the last vaccination (up to approximately 1 month) |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | R21/Matrix-M + DHA-PIP+PQ | The R21/Matrix-M vaccine (IM injection) + co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine R21/Matrix-M vaccination: R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2. DHA-PIP: Dihydroartemisinin/piperaquine tablets for adult patients 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. Participants 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. PQ: Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Community-acquired pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Malaise | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Lorenz von Seidlein | Mahidol-Oxford Tropical Medicine Research Unit (MORU) | +66-(0)2-3549170 | Lorenz@tropmedres.ac |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 9, 2022 | Mar 19, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 10, 2023 | Mar 17, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
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|
| DHA-PIP | Drug | Dihydroartemisinin/piperaquine tablets for adult patients 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. Participants 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. |
|
| PQ | Drug | Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered. |
|
| at study Month 2 |
| Number of Participants With Seroconversions in C-Term | Number of Participants with Seroconversions in C-Term | at study Month 3 |
| Number of Participants With Seroconversions in C-Term | Number of Participants with Seroconversions in C-Term | at study Month 6 |
| Number of Participants With Seroconversions in NANP | Number of Participants with Seroconversions in NANP | at study Month 1 |
| Number of Participants With Seroconversions in NANP | Number of Participants with Seroconversions in NANP | at study Month2 |
| Number of Participants With Seroconversions in NANP | Number of Participants with Seroconversions in NANP | at study Month 3 |
| Number of Participants With Seroconversions in NANP | Number of Participants with Seroconversions in NANP | at study Month 6 |
| Number of Participants With Seroconversions in R21 | Number of Participants with Seroconversions in R21 | at study Month 1 |
| Number of Participants With Seroconversions in R21 | Number of Participants with Seroconversions in R21 | at study Month 2 |
| Number of Participants With Seroconversions in R21 | Number of Participants with Seroconversions in R21 | at study Month 3 |
| Number of Participants With Seroconversions in R21 | Number of Participants With Seroconversions in R21 | at study Month 6 |
| Number of Participants With Seroconversions in HBsAg | Number of Participants with Seroconversions in HBsAg | at study Month 1 |
| Number of Participants With Seroconversions in HBsAg | Number of Participants with Seroconversions in HBsAg | at study Month 2 |
| Number of Participants With Seroconversions in HBsAg | Number of Participants with Seroconversions in HBsAg | at study Month 3 |
| Number of Participants With Seroconversions in HBsAg | Number of Participants with Seroconversions in HBsAg | at study Month 6 |
| For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (Cmax) following the administration of the antimalarials with or without vaccine | Study month 0 |
| For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (AUC) following the administration of the antimalarials with or without vaccine | Study month 0 |
| For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (Cmax) following the administration of the antimalarials with or without vaccine | Study month 1 |
| For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (AUC) following the administration of the antimalarials with or without vaccine | Study month 1 |
| For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (Cmax) following the administration of the antimalarials with or without vaccine | Study month 2 |
| For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (AUC) following the administration of the antimalarials with or without vaccine | Study month 2 |
| BG001 | R21/Matrix-M Only | The R21/Matrix-M vaccine (IM injection) only R21/Matrix-M vaccination: R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2. |
| BG002 | DHA-PIP+PQ Only | Co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine DHA-PIP: Dihydroartemisinin/piperaquine tablets for adult patients 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. Participants 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. PQ: Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Weight | Median | Inter-Quartile Range | Kg. |
|
| the heart rate-corrected QT (QTc) interval | Median | Inter-Quartile Range | Millisecond |
|
| Hemoglobin (Hb) | Mean | Standard Deviation | g/dL |
|
| White Blood Cell (WBC) | Mean | Inter-Quartile Range | 10^3 cells/Microliter |
|
| Platelets | Median | Inter-Quartile Range | 10^6 cells/Microliter |
|
| Creatinine | Median | Inter-Quartile Range | mg/dL |
|
| Aspartate Aminotransferase (AST) | Median | Inter-Quartile Range | U/L |
|
| Alanine Aminotransferase (ALT) | Median | Inter-Quartile Range | U/L |
|
| Temperature | Mean | Standard Deviation | ºC |
|
| OG001 | R21/Matrix-M Only | The R21/Matrix-M vaccine (IM injection) only R21/Matrix-M vaccination: R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2. |
| OG002 | DHA-PIP+PQ Only | Co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine DHA-PIP: Dihydroartemisinin/piperaquine tablets for adult patients 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. Participants 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. PQ: Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered. |
|
|
| Primary | Occurrence of Serious Adverse Events (SAEs), According to the MedRA Classification. | Posted | Count of Participants | Participants | During the whole study period, i.e. during a 6-month follow-up period from the receipt of first vaccination |
|
|
|
| Primary | Occurrence of Solicited Adverse Event Within 7 Days of Each Vaccination | Posted | Count of Participants | Participants | Within 7 days of each vaccination. |
|
|
|
| Secondary | Number of Participants With Seroconversions in C-Term | Number of Participants with Seroconversions in C-Term | Posted | Count of Participants | Participants | at study Month 1 |
|
|
|
| Secondary | Number of Participants With Seroconversions in C-Term | Number of Participants with Seroconversions in C-Term | Posted | Count of Participants | Participants | at study Month 2 |
|
|
|
| Secondary | Number of Participants With Seroconversions in C-Term | Number of Participants with Seroconversions in C-Term | Posted | Count of Participants | Participants | at study Month 3 |
|
|
|
| Secondary | Number of Participants With Seroconversions in C-Term | Number of Participants with Seroconversions in C-Term | Posted | Count of Participants | Participants | at study Month 6 |
|
|
|
| Secondary | Number of Participants With Seroconversions in NANP | Number of Participants with Seroconversions in NANP | Posted | Count of Participants | Participants | at study Month 1 |
|
|
|
| Secondary | Number of Participants With Seroconversions in NANP | Number of Participants with Seroconversions in NANP | Posted | Count of Participants | Participants | at study Month2 |
|
|
|
| Secondary | Number of Participants With Seroconversions in NANP | Number of Participants with Seroconversions in NANP | Posted | Count of Participants | Participants | at study Month 3 |
|
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|
| Secondary | Number of Participants With Seroconversions in NANP | Number of Participants with Seroconversions in NANP | Posted | Count of Participants | Participants | at study Month 6 |
|
|
|
| Secondary | Number of Participants With Seroconversions in R21 | Number of Participants with Seroconversions in R21 | Posted | Count of Participants | Participants | at study Month 1 |
|
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|
| Secondary | Number of Participants With Seroconversions in R21 | Number of Participants with Seroconversions in R21 | Posted | Count of Participants | Participants | at study Month 2 |
|
|
|
| Secondary | Number of Participants With Seroconversions in R21 | Number of Participants with Seroconversions in R21 | Posted | Count of Participants | Participants | at study Month 3 |
|
|
|
| Secondary | Number of Participants With Seroconversions in R21 | Number of Participants With Seroconversions in R21 | Posted | Count of Participants | Participants | at study Month 6 |
|
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| Secondary | Number of Participants With Seroconversions in HBsAg | Number of Participants with Seroconversions in HBsAg | Posted | Count of Participants | Participants | at study Month 1 |
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| Secondary | Number of Participants With Seroconversions in HBsAg | Number of Participants with Seroconversions in HBsAg | Posted | Count of Participants | Participants | at study Month 2 |
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| Secondary | Number of Participants With Seroconversions in HBsAg | Number of Participants with Seroconversions in HBsAg | Posted | Count of Participants | Participants | at study Month 3 |
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| Secondary | Number of Participants With Seroconversions in HBsAg | Number of Participants with Seroconversions in HBsAg | Posted | Count of Participants | Participants | at study Month 6 |
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| Secondary | For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (Cmax) following the administration of the antimalarials with or without vaccine | Posted | Median | Inter-Quartile Range | ng/mL | Study month 0 |
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| Secondary | For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (AUC) following the administration of the antimalarials with or without vaccine | Posted | Median | Inter-Quartile Range | ng*h/mL | Study month 0 |
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| Secondary | For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (Cmax) following the administration of the antimalarials with or without vaccine | Posted | Median | Inter-Quartile Range | ng/mL | Study month 1 |
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| Secondary | For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (AUC) following the administration of the antimalarials with or without vaccine | Posted | Median | Inter-Quartile Range | ng*h/mL | Study month 1 |
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| Secondary | For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (Cmax) following the administration of the antimalarials with or without vaccine | Posted | Median | Inter-Quartile Range | ng/mL | Study month 2 |
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| Secondary | For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine | For Arms 1 and 3, Piperaquine levels (AUC) following the administration of the antimalarials with or without vaccine | Posted | Median | Inter-Quartile Range | ng*h/mL | Study month 2 |
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| 0 |
| 52 |
| 1 |
| 52 |
| 38 |
| 52 |
| EG001 | R21/Matrix-M Only | The R21/Matrix-M vaccine (IM injection) only R21/Matrix-M vaccination: R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2. | 0 | 53 | 0 | 53 | 39 | 53 |
| EG002 | DHA-PIP+PQ Only | Co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine DHA-PIP: Dihydroartemisinin/piperaquine tablets for adult patients 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. Participants 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. PQ: Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered. | 0 | 22 | 1 | 22 | 5 | 22 |
| Optic neuritis with neuromyelitis optica (NMO) right eye | Eye disorders | Systematic Assessment |
|
| Fever | Infections and infestations | Systematic Assessment |
|
| ALT increased | Hepatobiliary disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Somnolence | Nervous system disorders | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Common cold | Infections and infestations | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | Non-systematic Assessment |
|
| Early menstruation | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Hepatobiliary disorders | Systematic Assessment |
|
| Allergic rhinitis | Immune system disorders | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| COVID-19 infection | Infections and infestations | Systematic Assessment |
|
| Community-acquired Pneumonia | Infections and infestations | Non-systematic Assessment |
|
| Cough | Infections and infestations | Non-systematic Assessment |
|
| Dysmenorrhea | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Dysplasia | General disorders | Non-systematic Assessment |
|
| Dysuria | Infections and infestations | Non-systematic Assessment |
|
| Eyebrow pain | General disorders | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Non-systematic Assessment |
|
| Insomnia | General disorders | Systematic Assessment |
|
| Lack of communication | General disorders | Systematic Assessment |
|
| Lack of concentration | General disorders | Systematic Assessment |
|
| Left/right jaw pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Neoplasm, Ovarian | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash at right little finger | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | Non-systematic Assessment |
|
| Running nose | Infections and infestations | Non-systematic Assessment |
|
| Sputum | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Stuffy nose | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Urticarial rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Anorexia | Gastrointestinal disorders | Systematic Assessment |
|
| optic neuritis | Nervous system disorders | Non-systematic Assessment |
|
| Sneeze | Infections and infestations | Non-systematic Assessment |
|
| viral infection | Infections and infestations | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Muscle pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Joint pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
|
| Pain | General disorders | Non-systematic Assessment |
|
| Redness | General disorders | Non-systematic Assessment |
|
| Swelling | General disorders | Non-systematic Assessment |
|
| Bruising | General disorders | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D000096724 |
| Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| Male |
|