Clinical trial NCT03521973: Safety, Tolerability and Protective Efficacy of PfSPZ Vaccine in Gabonese Children
Official title: Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess Safety, Tolerability and Protective Efficacy of PfSPZ Vaccine in 1-12 Year-old Gabonese Children Naturally Exposed to Malaria Parasites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: Plasmodium falciparum
PfSPZ Vaccine
Lead sponsor: Sanaria Inc.
Sponsor class: INDUSTRY
Collaborators: name: Centre de Recherches Médicales de Lambaréné (CERMEL), German Center for Infection Research
First posted: 2018-05-11
Enrollment: 200
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a single site, randomized, double-blind, placebo-controlled trial. The trial will assess the safety, tolerability, immunogenicity and vaccine efficacy (VE) of PfSPZ Vaccine in Gabonese children that are naturally exposed to malaria parasites. Healthy children aged 1- 12 years living in the surrounding areas of Lambaréné and/or Fougamou Province in Gabon will be eligible for participation.

Detailed description: The trial will be performed in 200 healthy Gabonese children, recruited across three age-strata: 7-12, 3-6 and 1-2 years (12-35 months). Within each age-stratum, volunteers will be randomized in a 2:1 ratio to receive three doses via direct venous inoculation (DVI) of either PfSPZ Vaccine (0.9x10\^6) or normal saline (NS) on days 0, 7 and 28 respectively; a minimum of 40 and a maximum of 100 volunteers are included in each of these age-strata.

In total, approximately 133 children will receive PfSPZ Vaccine and approximately 67 children will receive placebo. Randomization will be stratified by age-stratum, using permuted blocks of randomized size (3, 6, or 9). The start of inclusion into each age-stratum will be staggered, such that immunization of the first 3-6-year-olds will not commence until two weeks after start of immunization in the first 7-12-year-olds, and immunizations in the first 1-2-year-olds will not commence until two weeks after start of immunization in the first 3-6-year-olds. All volunteers will receive presumptive treatment with artemether-lumefantrine two weeks prior to final immunization (day 14). All volunteers will receive presumptive treatment with age-standardized 3-day course of oral artemether-lumefantrine (AL) \~two weeks prior to first immunization and again two weeks prior to final immunization.

Eligibility criteria: Inclusion Criteria:

* Healthy children aged 1 to 12 years
* Provision of written informed consent of a legal representative of age 18 or above and provision of informed assent by participants in concordance with Gabonese national guidelines.
* Able and willing to comply with all study requirements
* Residence in the area throughout the study period
* Household member reachable by mobile phone during the immunization phase

Exclusion Criteria:

* Receipt of an investigational product in the 30 days preceding enrollment
* Prior receipt of a malaria vaccine
* Immunization with more than 3 other vaccines or at least on elive vaccine within the past four weeks
* Use of immunoglobulins or blood products within 3 months prior to immunization with the investigational product
* Known or suspected HIV infection or any other immunosuppressive state
* Positive for hepatitis B surface antigen (HBs-antigen)
* Seropositive for hepatitis C virus (antibodies to HCV)
* A hemoglobin concentration \<9 g/dl (applies at enrollment only)
* History of non-febrile or atypical febrile seizures
* Pregnancy or lactation
* Any other significant disease, disorder or finding which, in the opinion of the investigator, may significantly increase the risk to the child because of participation in the study or impair interpretation of the study data

Primary outcomes:
measure: Proportion of volunteers who become parasitemic will be recorded, detected by Thick Blood Smear (TBS) microscopy
timeFrame: From 2 weeks to 6 months after the third PfSPZ Vaccine immunization
measure: Proportion of volunteers who become parasitemic with temperature ≥37.5°C or history of fever
timeFrame: From 2 weeks to 6 months after the third PfSPZ Vaccine immunization
measure: The occurrence and frequency of adverse events (AEs)
timeFrame: From the time of each PfSPZ Vaccine immunization until 7 days after each dose
measure: The occurrence and frequency of AEs
timeFrame: From the time of first PfSPZ Vaccine immunization until 28 days after the last dose
measure: The occurrence and frequency of serious adverse events (SAEs)
timeFrame: Around 27 months (from day of first immunization through study completion)
Secondary outcomes:
measure: The occurrence of all related solicited AE
timeFrame: From the time of each PfSPZ Vaccine immunization until 7 days after each dose
measure: The occurrence of all related unsolicited AEs
timeFrame: From the time of first PfSPZ Vaccine immunization until 28 days after the last dose
Other outcomes:
Locations:
city: Lambaréné
country: Gabon
facility: Centre de Recherches Médicales de Lambaréné (CERMEL)
state: Moyen-Ogooué
Study officials:
affiliation: Centre de Recherches Médicales de Lambaréné (CERMEL)
name: Selidji Agnandji, MD
role: PRINCIPAL_INVESTIGATOR
References: