Safety, Tolerability and Protective Efficacy of PfSPZ Vaccine in Gabonese Children

NCT ID: NCT03521973

Last Updated: 2021-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-14
• Study Completion Date: 2021-08-03

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1- PfSPZ-Vaccine

Children aged 7-12 years (inclusive) of age will be enrolled in this group.

N=44 will receive PfSPZ Vaccine; three doses of 9x10^6 PfSPZ of PfSPZ Vaccine administered by direct venous inoculation (DVI) given at 0, 7 and 28 day intervals.

Group Type: EXPERIMENTAL

PfSPZ Vaccine

Intervention Type: BIOLOGICAL

Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)

Group 2

Children aged 7-12 years (inclusive) of age will be enrolled in this group.

N=22 will receive normal saline; three doses of NS administered by DVI given at 0, 7 and 28 day intervals.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: OTHER

0.9% Sodium chloride

Group 3

Children aged 3-6 years (inclusive) of age will be enrolled in this group.

N=44 will receive PfSPZ Vaccine; three doses of 9x10^6 PfSPZ of PfSPZ Vaccine administered by direct venous inoculation (DVI) given at 0, 7 and 28 day intervals; given 2 weeks after the first immunization of Group 1.

Group Type: EXPERIMENTAL

PfSPZ Vaccine

Intervention Type: BIOLOGICAL

Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)

Group 4

Children aged 3-6 years (inclusive) of age will be enrolled in this group.

N=22 will receive normal saline; three doses of NS administered by DVI given at 0, 7 and 28 day intervals; given 2 weeks after the first dose of NS of Group 2.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: OTHER

0.9% Sodium chloride

Group 5

Children aged 1-2 years (inclusive) of age will be enrolled in this group.

N=44 will receive PfSPZ Vaccine; three doses of 9x10^6 PfSPZ of PfSPZ Vaccine administered by direct venous inoculation (DVI) given at 0, 7 and 28 day intervals; given 2 weeks after the first immunization of Group 3.

Group Type: EXPERIMENTAL

PfSPZ Vaccine

Intervention Type: BIOLOGICAL

Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)

Group 6

Children aged 1-2 years (inclusive) of age will be enrolled in this group.

N=22 will receive normal saline; three doses of NS administered by DVI given at 0, 7 and 28 day intervals; given 2 weeks after the first dose of NS of Group 4.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: OTHER

0.9% Sodium chloride

Interventions

PfSPZ Vaccine

Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)

Intervention Type: BIOLOGICAL

Normal Saline

0.9% Sodium chloride

Intervention Type: OTHER

Other Intervention Names

NS

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centre de Recherches Médicales de Lambaréné (CERMEL), German Center for Infection Research

UNKNOWN

Sponsor Role: collaborator

Sanaria Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Selidji Agnandji, MD

Role: PRINCIPAL_INVESTIGATOR

Centre de Recherches Médicales de Lambaréné (CERMEL)

Locations

Centre de Recherches Médicales de Lambaréné (CERMEL)

Lambaréné, Moyen-Ogooué Province, Gabon

Countries

Gabon

References

Agnandji ST, Bok J, Alabi A, Kabwende AL, Mbouna A, Bie J, Moukiti E, Lalremruata A, Esen M, Kreidenweiss A, Kc N, Sim BKL, Richie TL, Preston Church LW, McCall MBB, Hoffman SL, Kremsner PG, Mordmuller B. Safety, tolerability, and protective efficacy of a radiation-attenuated, whole sporozoite malaria vaccine in children in Gabon: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2025 Sep 16:S1473-3099(25)00434-7. doi: 10.1016/S1473-3099(25)00434-7. Online ahead of print.

Reference Type: DERIVED

PMID: 40972633 (View on PubMed)

Other Identifiers

LaSPZV1

Identifier Type: -

Identifier Source: org_study_id