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

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

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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Other: Normal Saline; Biological: PfSPZ Vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Gabon
  • Moyen-Ogooué
    • Lambaréné, Moyen-Ogooué, Gabon
      • Centre de Recherches Médicales de Lambaréné (CERMEL)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 12 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: PfSPZ Vaccine; Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)
Placebo Comparator: 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.	Other: Normal Saline; 0.9% Sodium chloride; Other Names: NS
Experimental: 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.	Biological: PfSPZ Vaccine; Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)
Placebo Comparator: 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.	Other: Normal Saline; 0.9% Sodium chloride; Other Names: NS
Experimental: 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.	Biological: PfSPZ Vaccine; Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)
Placebo Comparator: 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.	Other: Normal Saline; 0.9% Sodium chloride; Other Names: NS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of volunteers who become parasitemic will be recorded, detected by Thick Blood Smear (TBS) microscopy	Time to event and proportional analysis of episodes of P. falciparum parasitemia, detected actively or passively by TBS microscopy. Vaccine efficacy will be measured in the mITT population.	From 2 weeks to 6 months after the third PfSPZ Vaccine immunization
Proportion of volunteers who become parasitemic with temperature ≥37.5°C or history of fever	Time to event and proportional analysis of episodes of P. falciparum parasitemia with temperature ≥37.5°C or history of fever within the last 24 hours (P. falciparum malaria with clinical manifestations). Vaccine efficacy against P. falciparum malaria with clinical manifestations will be measured in the mITT population using hierarchical testing; the secondary will only be tested when the primary endpoint shows a significant difference.	From 2 weeks to 6 months after the third PfSPZ Vaccine immunization
The occurrence and frequency of adverse events (AEs)	The occurrence and frequency of Grade 3 solicited adverse AEs (related or unrelated) after vaccination	From the time of each PfSPZ Vaccine immunization until 7 days after each dose
The occurrence and frequency of AEs	The occurrence and frequency of Grade 3 unsolicited adverse AEs (related or unrelated) after vaccination	From the time of first PfSPZ Vaccine immunization until 28 days after the last dose
The occurrence and frequency of serious adverse events (SAEs)	The occurrence and frequency of SAEs (related or unrelated) after vaccination	Around 27 months (from day of first immunization through study completion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of all related solicited AE	The occurrence of all related solicited AE after vaccination	From the time of each PfSPZ Vaccine immunization until 7 days after each dose
The occurrence of all related unsolicited AEs	The occurrence of all related unsolicited AE after vaccination	From the time of first PfSPZ Vaccine immunization until 28 days after the last dose

Collaborators and Investigators

• Sponsor: Sanaria Inc.
• Collaborators: Centre de Recherches Médicales de Lambaréné (CERMEL), German Center for Infection Research
• Investigators: Principal Investigator: Selidji Agnandji, MD, Centre de Recherches Médicales de Lambaréné (CERMEL)

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2018
• Primary Completion (Actual): May 18, 2021
• Study Completion (Actual): August 3, 2021

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 9, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): October 7, 2021
• Last Update Submitted That Met QC Criteria: October 6, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: PfSPZ Vaccine; Plasmodium falciparum
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: LaSPZV1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No