Back to resultsMSP3-CRM-Vac4All/ Alhydrogel® Vaccine
Primary Purpose
Malaria,Falciparum
Status
Recruiting
Phase
Phase 1
Locations
Mali
Study Type
Interventional
Intervention
MSP3-CRM-Vac4All/ Alhydrogel®
Anti-Rabies Vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Malaria,Falciparum focused on measuring malaria, malaria vaccine, vaccine efficacy
Eligibility Criteria
Inclusion Criteria: Children aged 12-59 months years old Healthy by medical history, physical examination and laboratory investigation Signed/thumb printed informed Consent by guardian/parent Resident in the study area villages during the whole trial period Exclusion Criteria: Symptoms, physical signs of disease that could interfere with the interpretation of the trial results or compromising the health of the participants Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior recruitment. (For corticosteroids, this will mean prednisone, or equivalent, more or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.) Cannot be followed for any social, psychological or geographical reasons. Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose. Suspected or known hypersensitivity to any of the vaccine components or to previous vaccine. Clinically significant laboratory abnormalities on screened blood samples. Planned administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine. An exception, is the receipt of an childhood immunization program or licensed vaccine (measles, oral polio, Hib, meningococcal and combined diphtheria/pertussis/tetanus vaccines) which may be given before or after vaccination*. Evidence of chronic or active hepatitis B or C infection Presence of chronic illness that, in the judgment of the investigator, would interfere with the study outcomes or pose a threat to the participant's health. Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period History of surgical splenectomy. Moderate or severe malnutrition at screening based on clinical judgement. o (Weight-for-age Z score of less than -3 or other clinical signs of malnutrition). Previous participation to a malaria vaccine trial Known history of HIV infection
Sites / Locations
- Malaria Research and Training Center (MRTC), University of Sciences Techniques and Technologies of Bamako, MaliRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Test Vaccine
Control Vaccine
Arm Description
MSP3-CRM-Vac4All/ Alhydrogel®
Anti-rabies vaccine
Outcomes
Primary Outcome Measures
Protective Efficacy against Clinical Malaria
To assess the efficacy of 30 µg MSP3-CRM-Vac4All/Alhydrogel® vaccine in children ages 12-60 months old, against clinical malaria occurring over one transmission season.
The primary efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
Secondary Outcome Measures
Efficacy- different definitions of malaria fever and parasite thresholds on microscopy
To compare efficacy against clinical malaria for different case definitions using
Fever thresholds that are higher than 37.5ºC, such as 38.5ºC and 39.5ºC
History of fever instead of measured fever
Different parasitemia by microscopy thresholds [any parasitemia, 1000, 10,000 and 20,000/µL]
Efficacy outcomes
clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 38.5ºC with P. falciparum parasitemia ≥5000/µL or ≥ 39.5ºC with P. falciparum parasitemia ≥5000/µL or
clinical malaria episodes defined as history of fever with P. falciparum parasitemia of the following levels: any parasitemia, 1000, 10,000 and 20,000/µL clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 38.5ºC with or ≥ 39.5ºC with P. falciparum parasitemia of the following levels: any parasitemia, 1000, 10,000 and 20,000/µL
Efficacy duration
To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring during the 12 months following dose 3.
Efficacy against first malaria episodes
To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against first clinical malaria episodes occurring from over the 6 month period 14 days after 2nd and 3rd vaccination and up to the end of study follow-up (12 months after first vaccination).
The efficacy outcome is first episode of clinical malaria, with the case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
Efficacy (conditional boost)
To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring The efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
Efficacy (conditional boost)
To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring.
The efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
Number of adverse events
To assess the safety and reactogenicity of 3 doses of 30 µg MSP3-CRM-Vac4All/Alhydrogel® given at D0, D28 and D56 in healthy young children
Number of adverse events for conditional boost vaccination
Safety and reactogenicity of boost vaccination doses of MSP3-CRM-Vac4All/Alhydrogel® in healthy young children
Immune response
To examine the duration of immune responses of a 3-dose regimen of during periods corresponding to that used for primary and other secondary efficacy endpoints as measured through a > 5-fold decrease of MSP3-specific serum IgG antibody titers after each vaccination in comparison to baseline levels (14 days post last dose)
Immune response
To determine immunogenicity in terms of the proportion with titres either more than 3SD above the median for negative controls (positive) or at least 50% of the positive controls (strongly positive) after dose 3.
Parasite densities
To measure effect on parasitemia by comparing parasite densities in malaria episodes occurring in vaccinees compared to control
Full Information
NCT ID
NCT05776017
First Posted
February 25, 2023
Last Updated
April 24, 2023
Sponsor
Vac4All
Collaborators
Malaria Research and Training Center, Bamako, Mali
1. Study Identification
Unique Protocol Identification Number
NCT05776017
Brief Title
MSP3-CRM-Vac4All/ Alhydrogel® Vaccine
Official Title
A Phase 1b/2b Double Blind, Randomized, Controlled Study of the Safety, Immunogenicity, and Efficacy of Malaria Vaccine Candidate MSP3-CRM-Vac4All/ Alhydrogel® in Young Children in Mali
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 27, 2023 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vac4All
Collaborators
Malaria Research and Training Center, Bamako, Mali
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
Two-arm, randomized, double-blinded and controlled clinical trial to first assess the safety and tolerability of the vaccine in a Phase 1b trial and proceed to assess its efficacy against clinical malaria in young children living in highly seasonal malaria areas of Mali
Detailed Description
This study is designed to be executed in two steps to achieve the primary efficacy objective:
The first step is a Phase 1b safety study, involving injections in a small safety subgroup for each dose before age-de-escalation into the younger age group and then proceeding to the second step of dosing the corresponding injection in the larger Phase 2b efficacy cohort.
Vaccination of the Phase 2b cohort will require an acceptable reactogenicity data over the first week following the corresponding vaccination of the older and younger age groups in the Phase 1 subgroup. The study DSMB will be charged with this review and ensuring that vaccination proceeds only if the reactogenicity profile meet study "go" criteria (Table 1).
The objectives of each phase are:
Phase 1b: The primary objective is to assess the safety and tolerability of the vaccine for each injection. The secondary objective is to evaluate the immune response to the vaccine and safety for up to 12 months after the first dose.
Phase 2b: The primary objective is to assess the efficacy in young children* against clinical malaria** during one transmission season. The timeline for the primary analysis assessment is from 14 days to 6 months after Dose 3.
Should the primary analysis data demonstrate that the vaccine gives good efficacy, a boost vaccination will be programmed to be administered to willing subjects before the start of the subsequent transmission season. The study protocol will be amended with the precise details in this event.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria,Falciparum
Keywords
malaria, malaria vaccine, vaccine efficacy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Vaccine recipients and their parent(s)/guardian(s) as well as all investigators and study personnel responsible for the vaccination, evaluation of safety and immunogenicity endpoints will all be unaware to the exact treatment given to the participant. Randomization will be programmed into the eCRF, as subjects are confirmed to be eligible for enrollment and to be vaccinated. A password protected electronic randomized vaccination allocation list will be sent to the designated vaccine pharmacist. The investigator will send a request for vaccination to the pharmacy using the subject randomization number (which will be the subject unique ID number) assigned by the eCRF. For each child, eligibility will have to be counter checked and signed by a second person before allocation of study ID number.
Allocation
Randomized
Enrollment
465 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Test Vaccine
Arm Type
Experimental
Arm Description
MSP3-CRM-Vac4All/ Alhydrogel®
Arm Title
Control Vaccine
Arm Type
Active Comparator
Arm Description
Anti-rabies vaccine
Intervention Type
Biological
Intervention Name(s)
MSP3-CRM-Vac4All/ Alhydrogel®
Intervention Description
30 microgram MSP3-CRM-Vac4All protein extemporaneously formulated with Alhydrogel® adjuvant
Intervention Type
Biological
Intervention Name(s)
Anti-Rabies Vaccine
Intervention Description
Control vaccine
Primary Outcome Measure Information:
Title
Protective Efficacy against Clinical Malaria
Description
To assess the efficacy of 30 µg MSP3-CRM-Vac4All/Alhydrogel® vaccine in children ages 12-60 months old, against clinical malaria occurring over one transmission season.
The primary efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
Time Frame
The timeline for assessment will be from 14 days to 6 months after Dose 3.
Secondary Outcome Measure Information:
Title
Efficacy- different definitions of malaria fever and parasite thresholds on microscopy
Description
To compare efficacy against clinical malaria for different case definitions using
Fever thresholds that are higher than 37.5ºC, such as 38.5ºC and 39.5ºC
History of fever instead of measured fever
Different parasitemia by microscopy thresholds [any parasitemia, 1000, 10,000 and 20,000/µL]
Efficacy outcomes
clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 38.5ºC with P. falciparum parasitemia ≥5000/µL or ≥ 39.5ºC with P. falciparum parasitemia ≥5000/µL or
clinical malaria episodes defined as history of fever with P. falciparum parasitemia of the following levels: any parasitemia, 1000, 10,000 and 20,000/µL clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 38.5ºC with or ≥ 39.5ºC with P. falciparum parasitemia of the following levels: any parasitemia, 1000, 10,000 and 20,000/µL
Time Frame
For 12 months after first vaccination
Title
Efficacy duration
Description
To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring during the 12 months following dose 3.
Time Frame
For 12 months following the first vaccination
Title
Efficacy against first malaria episodes
Description
To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against first clinical malaria episodes occurring from over the 6 month period 14 days after 2nd and 3rd vaccination and up to the end of study follow-up (12 months after first vaccination).
The efficacy outcome is first episode of clinical malaria, with the case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
Time Frame
From 14 days post 2nd or 3rd vaccination to 6 months following and up to the end of study follow-up (12 months after first vaccination
Title
Efficacy (conditional boost)
Description
To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring The efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
Time Frame
For the 6 months following boost vaccination
Title
Efficacy (conditional boost)
Description
To assess the efficacy of MSP3-CRM-Vac4All/Alhydrogel® in young children against clinical malaria occurring.
The efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
Time Frame
For the 12 months following boost vaccination
Title
Number of adverse events
Description
To assess the safety and reactogenicity of 3 doses of 30 µg MSP3-CRM-Vac4All/Alhydrogel® given at D0, D28 and D56 in healthy young children
Time Frame
During the month following each vaccination, and 6 months and 12 months after first vaccination.
Title
Number of adverse events for conditional boost vaccination
Description
Safety and reactogenicity of boost vaccination doses of MSP3-CRM-Vac4All/Alhydrogel® in healthy young children
Time Frame
At one month, 6 month and 12 months following boost vaccination
Title
Immune response
Description
To examine the duration of immune responses of a 3-dose regimen of during periods corresponding to that used for primary and other secondary efficacy endpoints as measured through a > 5-fold decrease of MSP3-specific serum IgG antibody titers after each vaccination in comparison to baseline levels (14 days post last dose)
Time Frame
From 14 days post last dose to up to a month after last dose, 6 months after last dose and 12 months after first dose
Title
Immune response
Description
To determine immunogenicity in terms of the proportion with titres either more than 3SD above the median for negative controls (positive) or at least 50% of the positive controls (strongly positive) after dose 3.
Time Frame
A month after dose 3
Title
Parasite densities
Description
To measure effect on parasitemia by comparing parasite densities in malaria episodes occurring in vaccinees compared to control
Time Frame
From vaccination to up to 6 months after last dose and 12 months after first dose.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
59 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Children aged 12-59 months years old
Healthy by medical history, physical examination and laboratory investigation
Signed/thumb printed informed Consent by guardian/parent
Resident in the study area villages during the whole trial period
Exclusion Criteria:
Symptoms, physical signs of disease that could interfere with the interpretation of the trial results or compromising the health of the participants
Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior recruitment. (For corticosteroids, this will mean prednisone, or equivalent, more or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
Cannot be followed for any social, psychological or geographical reasons.
Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose.
Suspected or known hypersensitivity to any of the vaccine components or to previous vaccine.
Clinically significant laboratory abnormalities on screened blood samples.
Planned administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine. An exception, is the receipt of an childhood immunization program or licensed vaccine (measles, oral polio, Hib, meningococcal and combined diphtheria/pertussis/tetanus vaccines) which may be given before or after vaccination*.
Evidence of chronic or active hepatitis B or C infection
Presence of chronic illness that, in the judgment of the investigator, would interfere with the study outcomes or pose a threat to the participant's health.
Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period
History of surgical splenectomy.
Moderate or severe malnutrition at screening based on clinical judgement.
o (Weight-for-age Z score of less than -3 or other clinical signs of malnutrition).
Previous participation to a malaria vaccine trial
Known history of HIV infection
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zarifah H Reed, MD, MPH
Phone
+33695695786
Email
zahussain22@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manamadou Thera, MD
Organizational Affiliation
MRTC, University of Sciences Techniques and Technologies of Bamako, Mali Locations:
Official's Role
Study Director
Facility Information:
Facility Name
Malaria Research and Training Center (MRTC), University of Sciences Techniques and Technologies of Bamako, Mali
City
Bamako
ZIP/Postal Code
1805
Country
Mali
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mahamadou Thera, MD
Phone
+223 66 74 09 61
Email
mthera@icermali.org
First Name & Middle Initial & Last Name & Degree
Karim Traore
Phone
+223 66 72 50 63
Email
Karim@icermali.org
First Name & Middle Initial & Last Name & Degree
Drissa Coulibaly, MD
First Name & Middle Initial & Last Name & Degree
Moctar Coulibaly, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
MSP3-CRM-Vac4All/ Alhydrogel® Vaccine
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