MSP3-CRM-Vac4All/ Alhydrogel® Vaccine
- 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
- Short 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
- Control arm
- Active comparator
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Unknown
- Phase
- Phase 1/Phase 2
- Study type
- Interventional
- Completion date
- 2024-08-31
- First posted
- 2023-03-20
- Registry last updated
- 2023-04-26
- Primary completion date
- 2023-12-31
- Start date
- 2023-03-27
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Vac4All
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05776017
- ClinicalTrials.gov ID
- NCT05776017
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Parallel groups
- Purpose
- Prevention
- Masking
- Quadruple masking
- 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.
- Masked roles
- Participants, Care providers, Investigators, Outcome assessors
Protective Efficacy against Clinical Malaria
Timeframe: The timeline for assessment will be from 14 days to 6 months after Dose 3.
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
Efficacy- different definitions of malaria fever and parasite thresholds on microscopy
Timeframe: For 12 months after first vaccination
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
Timeframe: For 12 months following the first vaccination
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
Timeframe: 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
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)
Timeframe: For the 6 months following boost vaccination
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)
Timeframe: For the 12 months following boost vaccination
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
Timeframe: During the month following each vaccination, and 6 months and 12 months after first vaccination.
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
Timeframe: At one month, 6 month and 12 months following boost vaccination
Safety and reactogenicity of boost vaccination doses of MSP3-CRM-Vac4All/Alhydrogel® in healthy young children
Immune response
Timeframe: 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
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
Timeframe: A month after dose 3
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
Timeframe: From vaccination to up to 6 months after last dose and 12 months after first dose.
To measure effect on parasitemia by comparing parasite densities in malaria episodes occurring in vaccinees compared to control
- Sex
- All
- Age groups
- Children
- Minimum age
- 12 Months
- Maximum age
- 59 Months
- Healthy volunteers
- Yes
- 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
-
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
- Malaria Research and Training Center (MRTC), University of Sciences Techniques and Technologies of Bamako, MaliBamako, MaliRecruiting
Related records
Drugs (2)
Collaborators (1)
- Malaria Research and Training Center, Bamako, Mali
Lead sponsors (1)
Conditions (2)
- Malaria
- Plasmodium falciparum malaria Primary condition