Clinical trial NCT05776017: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Malaria,Falciparum
Keywords: malaria
malaria vaccine
vaccine efficacy
Lead sponsor: Vac4All
Sponsor class: INDUSTRY
Collaborators: name: Malaria Research and Training Center, Bamako, Mali
First posted: 2023-03-20
Enrollment: 465
Sex: ALL
Minimum age (years): 12
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Protective Efficacy against Clinical Malaria
timeFrame: The timeline for assessment will be from 14 days to 6 months after Dose 3.
Secondary outcomes:
measure: Efficacy- different definitions of malaria fever and parasite thresholds on microscopy
timeFrame: For 12 months after first vaccination
measure: Efficacy duration
timeFrame: For 12 months following the first vaccination
measure: 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
measure: Efficacy (conditional boost)
timeFrame: For the 6 months following boost vaccination
measure: Efficacy (conditional boost)
timeFrame: For the 12 months following boost vaccination
measure: Number of adverse events
timeFrame: During the month following each vaccination, and 6 months and 12 months after first vaccination.
measure: Number of adverse events for conditional boost vaccination
timeFrame: At one month, 6 month and 12 months following boost vaccination
measure: 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
measure: Immune response
timeFrame: A month after dose 3
measure: Parasite densities
timeFrame: From vaccination to up to 6 months after last dose and 12 months after first dose.
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: Malaria Research and Training Center (MRTC), University of Sciences Techniques and Technologies of Bamako, Mali
Study officials:
affiliation: MRTC, University of Sciences Techniques and Technologies of Bamako, Mali Locations:
name: Manamadou Thera, MD
role: STUDY_DIRECTOR
References: