Back to resultsA Study to Test Experimental Blood Stage Malaria Vaccine in Burkina Faso.
Primary Purpose
Malaria,Falciparum
Status
Recruiting
Phase
Phase 1
Locations
Burkina Faso
Study Type
Interventional
Intervention
Rabies vaccine
RH5.1 10μg adjuvated with 50μg Matrix-M
RH5.2 5μg adjuvated with 50μg Matrix-M
Sponsored by
About this trial
This is an interventional prevention trial for Malaria,Falciparum
Eligibility Criteria
Inclusion Criteria: Healthy infant aged 5-17 months at the time of first study vaccination Parent/guardian provides signed/thumb-printed informed consent Infant and parent/guardian resident in the study area villages and anticipated to be available for vaccination and follow-up for 12 months following last dose of vaccination. Exclusion Criteria: Clinically significant congenital abnormalities as judged by the PI or other delegated individual. Clinically significant skin disorder (psoriasis, contact dermatitis etc.), cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness as judged by the PI or other delegated individual. Weight-for-age Z score of less than -3 or other clinical signs of malnutrition. History of allergic reaction, significant IgE-mediated event, or anaphylaxis to immunization. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Sickle cell disease. Clinically significant laboratory abnormality as judged by the study clinician. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. Receipt of any vaccine in the 7 days preceding enrolment, or planned receipt of any other vaccine within 7 days following each study vaccination. History of vaccination with another malaria vaccine. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. Known maternal HIV infection (no testing will be done by the study team). Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (for corticosteroids, this will mean prednisone, or equivalent, ≥0.5 mg/kg/day; inhaled and topical steroids are allowed). Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
Sites / Locations
- Institut de Recherche en Sciences de la SantéRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Arm Label
Group 1 (Control group)
Group 2
Group 3 (Control Group)
Group 4
Group 5
Arm Description
n= 60. Age= 5-17 months Rabies Vaccine administered on Days 0, 28 and 152.
n=120 Age= 5-17 months First vaccination of RH5.1 10μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 152.
n= 60. Age= 5-17 months Rabies Vaccine administered on Days 0, 28 and 56.
n=120 Age= 5-17 months First vaccination of RH5.1 10μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 56.
n=120 Age= 5-17 months First vaccination of RH5.2-VLP 5μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 56.
Outcomes
Primary Outcome Measures
To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area for 6 months after the last vaccination.
Time to first episode of clinical malaria (defined as the presence of axillary temperature higher than 37.5 degree celsius and P. Falciparum parasite density >5000 asexual forms/µL)
To assess the safety and reactogenicity of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area.
Occurrence of solicited systemic reactogenicity signs and symptoms via clinic and home visits
Secondary Outcome Measures
To assess the humoral immunogenicity of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area.
The following measures will be assessed
Serum ELISA response:
1. Quantitative antigen-specific IgG antibody levels (µg/mL readout) over time - analysis of peak responses and longevity; 2. Antigen-specific antibody subclass/isotype measurement; 3. Antigen-specific antibody avidity measurement; In vitro GIA against 3D7 clone P. falciparum parasites using purified total IgG and a single-cycle pLDH readout assay
Purified IgG ELISA versus GIA titration "Quality Analysis"
To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area for 3 months after the last vaccination.
Time to first episode of clinical malaria (defined as the presence of axillary temperature ≥37.5°C and P. falciparum parasite density >5000 asexual forms/µL).
To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area
Occurrence of solicited local reactogenicity signs and symptoms via clinic and home visits
To assess the protective efficacy against asymptomatic P. falciparum infection of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area, by qPCR.
Efficacy tested by conducting qPCR analysis
To assess the protective efficacy against asymptomatic P. falciparum infection against gametocytaemia of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area, by qPCR.
The proportion of participants in each study arm that show presence of parasite density >5000 asexual forms/µL as measured by quantitative reverse-transcriptase PCR PLUS presence of axillary temperature <37.5°C and absence of history of fever within the last 24 hours. The proportion of participants in each study arm that show presence of parasite density >0 asexual forms/µL as measured by quantitative reverse-transcriptase PCR PLUS presence of axillary temperature <37.5°C and absence of history of fever within the last 24 hours.
To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-M and RH5.2-VLP in Matrix-M in 5-17 months old children living in a malaria-endemic area for 12 months after the last vaccination.
Time to first episode of clinical malaria (defined as the presence of axillary temperature ≥37.5°C and P. falciparum parasite density >5000 asexual forms/µL).
To assess the protective efficacy against gametocytaemia of RH5.1 in Matrix-M and RH5.2-VLP in Matrix-M in 5-17 months old children living in a malaria-endemic area, by qPCR at 2 and 6 months after administration of the final dose of vaccine
The proportion of participants in each study arm that show presence of gametocytes >0 gametocytes/μL as measured by quantitative reverse-transcriptase PCR.
Efficacy against incident severe anaemia and blood transfusion requirement
The proportion of participants in each study arm with documented Hb <5.0 g/dL identified at clinical presentation in association with P. falciparum asexual parasitaemia > 5000 parasites/µL. The proportion of participants in each study arm with documented Hb <5.0 g/dL identified at clinical presentation and requirement for a blood transfusion.
Full Information
NCT ID
NCT05790889
First Posted
January 16, 2023
Last Updated
October 19, 2023
Sponsor
University of Oxford
1. Study Identification
Unique Protocol Identification Number
NCT05790889
Brief Title
A Study to Test Experimental Blood Stage Malaria Vaccine in Burkina Faso.
Official Title
A Phase IIb Randomised Controlled Trial of the Safety, Immunogenicity and Efficacy of the Blood-stage Malaria Vaccine Candidates RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in Infants Aged 5-17 Months in Burkina Faso.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 3, 2023 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase IIb randomised controlled trial of the safety, immunogenicity and efficacy of the blood-stage malaria vaccine candidates RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in infants aged 5-17 months in Burkina Faso
Detailed Description
During the initial recruitment to Groups 1 and 2, participants will be randomised 1:2 to receive vaccination with the rabies control vaccination or RH5.1/Matrix-M.
During recruitment to Groups 3, 4 and 5, participants will be randomised 1:2:2 to receive vaccination with rabies control vaccination, RH5.1/Matrix-M or RH5.2-VLP/Matrix-M Efficacy of vaccination will be assessed by comparing the incidence of malaria cases in the pooled control groups (Groups 1 and 3) to the incidence of malaria in each investigational vaccine group (Groups 2,4 and 5).
There are three study vaccines: the IMP, 10μg RH5.1 adjuvanted with Matrix-M; 5μg RH5.2-VLP and Rabies Vaccine. Participants will receive the first vaccination of RH5.1 10μg with 50μg Matrix-M (Groups 2 and 4) or RH5.2 5μg with 50μg Matrix-M (Group 5). After approximately 4 weeks, a second dose will be administered, followed by a third and final vaccination approximately 4 weeks later (Groups 3-5) or approximately 4 months later (Groups 1-2). Second and third vaccinations will be administered at the same dose of both vaccine and adjuvant as at the initial vaccination and will be given within the window period of 5 months. Volunteers will be followed for 12 months from final vaccination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria,Falciparum
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
480 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group 1 (Control group)
Arm Type
Placebo Comparator
Arm Description
n= 60. Age= 5-17 months Rabies Vaccine administered on Days 0, 28 and 152.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
n=120 Age= 5-17 months First vaccination of RH5.1 10μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 152.
Arm Title
Group 3 (Control Group)
Arm Type
Placebo Comparator
Arm Description
n= 60. Age= 5-17 months Rabies Vaccine administered on Days 0, 28 and 56.
Arm Title
Group 4
Arm Type
Experimental
Arm Description
n=120 Age= 5-17 months First vaccination of RH5.1 10μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 56.
Arm Title
Group 5
Arm Type
Experimental
Arm Description
n=120 Age= 5-17 months First vaccination of RH5.2-VLP 5μg with 50μg Matrix-M will be administered on day 0, followed by a second dose administered on Day 28, followed by a third and final dose at Day 56.
Intervention Type
Biological
Intervention Name(s)
Rabies vaccine
Intervention Description
Vaccine
Intervention Type
Biological
Intervention Name(s)
RH5.1 10μg adjuvated with 50μg Matrix-M
Intervention Description
Vaccine
Intervention Type
Biological
Intervention Name(s)
RH5.2 5μg adjuvated with 50μg Matrix-M
Intervention Description
Vaccine
Primary Outcome Measure Information:
Title
To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area for 6 months after the last vaccination.
Description
Time to first episode of clinical malaria (defined as the presence of axillary temperature higher than 37.5 degree celsius and P. Falciparum parasite density >5000 asexual forms/µL)
Time Frame
From 14 days after the third study vaccination until 6 months after the third study vaccination.
Title
To assess the safety and reactogenicity of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area.
Description
Occurrence of solicited systemic reactogenicity signs and symptoms via clinic and home visits
Time Frame
The month following each vaccination and at 6 and 12 months after administration of the final dose of vaccine.
Secondary Outcome Measure Information:
Title
To assess the humoral immunogenicity of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area.
Description
The following measures will be assessed
Serum ELISA response:
1. Quantitative antigen-specific IgG antibody levels (µg/mL readout) over time - analysis of peak responses and longevity; 2. Antigen-specific antibody subclass/isotype measurement; 3. Antigen-specific antibody avidity measurement; In vitro GIA against 3D7 clone P. falciparum parasites using purified total IgG and a single-cycle pLDH readout assay
Purified IgG ELISA versus GIA titration "Quality Analysis"
Time Frame
Immunology blood samples will be collected at screening, day of vaccination (V) 1, 14 & 28 days post V2, day of V3, 14 days post V3, 2, 6 and 12 months post V3.
Title
To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area for 3 months after the last vaccination.
Description
Time to first episode of clinical malaria (defined as the presence of axillary temperature ≥37.5°C and P. falciparum parasite density >5000 asexual forms/µL).
Time Frame
From 14 days after the third study vaccination until 3 months after the third study vaccination
Title
To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area
Description
Occurrence of solicited local reactogenicity signs and symptoms via clinic and home visits
Time Frame
For 12 months after the last vaccination
Title
To assess the protective efficacy against asymptomatic P. falciparum infection of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area, by qPCR.
Description
Efficacy tested by conducting qPCR analysis
Time Frame
At 6 and 12 months after administration of the final dose of vaccine.
Title
To assess the protective efficacy against asymptomatic P. falciparum infection against gametocytaemia of RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in 5-17 months old children living in a malaria-endemic area, by qPCR.
Description
The proportion of participants in each study arm that show presence of parasite density >5000 asexual forms/µL as measured by quantitative reverse-transcriptase PCR PLUS presence of axillary temperature <37.5°C and absence of history of fever within the last 24 hours. The proportion of participants in each study arm that show presence of parasite density >0 asexual forms/µL as measured by quantitative reverse-transcriptase PCR PLUS presence of axillary temperature <37.5°C and absence of history of fever within the last 24 hours.
Time Frame
At 6 and 12 months post third study vaccination.
Title
To assess the protective efficacy against clinical malaria of RH5.1 in Matrix-M and RH5.2-VLP in Matrix-M in 5-17 months old children living in a malaria-endemic area for 12 months after the last vaccination.
Description
Time to first episode of clinical malaria (defined as the presence of axillary temperature ≥37.5°C and P. falciparum parasite density >5000 asexual forms/µL).
Time Frame
From 14 days after the third study vaccination until 12 months after the third study vaccination
Title
To assess the protective efficacy against gametocytaemia of RH5.1 in Matrix-M and RH5.2-VLP in Matrix-M in 5-17 months old children living in a malaria-endemic area, by qPCR at 2 and 6 months after administration of the final dose of vaccine
Description
The proportion of participants in each study arm that show presence of gametocytes >0 gametocytes/μL as measured by quantitative reverse-transcriptase PCR.
Time Frame
At 2 and 6 months post third study vaccination.
Title
Efficacy against incident severe anaemia and blood transfusion requirement
Description
The proportion of participants in each study arm with documented Hb <5.0 g/dL identified at clinical presentation in association with P. falciparum asexual parasitaemia > 5000 parasites/µL. The proportion of participants in each study arm with documented Hb <5.0 g/dL identified at clinical presentation and requirement for a blood transfusion.
Time Frame
From 14 days after the third study vaccination until 6 months after the third study vaccination.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Months
Maximum Age & Unit of Time
17 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy infant aged 5-17 months at the time of first study vaccination
Parent/guardian provides signed/thumb-printed informed consent
Infant and parent/guardian resident in the study area villages and anticipated to be available for vaccination and follow-up for 12 months following last dose of vaccination.
Exclusion Criteria:
Clinically significant congenital abnormalities as judged by the PI or other delegated individual.
Clinically significant skin disorder (psoriasis, contact dermatitis etc.), cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness as judged by the PI or other delegated individual.
Weight-for-age Z score of less than -3 or other clinical signs of malnutrition.
History of allergic reaction, significant IgE-mediated event, or anaphylaxis to immunization.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
Sickle cell disease.
Clinically significant laboratory abnormality as judged by the study clinician.
Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
Receipt of any vaccine in the 7 days preceding enrolment, or planned receipt of any other vaccine within 7 days following each study vaccination.
History of vaccination with another malaria vaccine.
Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
Known maternal HIV infection (no testing will be done by the study team).
Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (for corticosteroids, this will mean prednisone, or equivalent, ≥0.5 mg/kg/day; inhaled and topical steroids are allowed).
Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jee-Sun Cho
Phone
+44 (0)1865 611418
Email
vaccinetrials@ndm.ox.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angela Minassian
Organizational Affiliation
Honorary Consultant and Chief Investigator - Project clinical trials
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut de Recherche en Sciences de la Santé
City
Sigle
State/Province
Boulkiemdé Province
ZIP/Postal Code
BP 7192 OUAGADOUGOU 03, BF
Country
Burkina Faso
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Athanase M. Somé, Doctorat en médecine
Phone
25446249
Ext
+226
Email
athanasesome@crun.bf
First Name & Middle Initial & Last Name & Degree
Dr Hermann Sorgho
First Name & Middle Initial & Last Name & Degree
Dr Ousmane Traoré
First Name & Middle Initial & Last Name & Degree
Dr Salou Diallo
First Name & Middle Initial & Last Name & Degree
Dr Toussaint Rouamba
12. IPD Sharing Statement
Learn more about this trial
A Study to Test Experimental Blood Stage Malaria Vaccine in Burkina Faso.
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