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

Primary Purpose

Malaria

Status
Completed
Phase
Phase 2
Locations
Gabon
Study Type
Interventional
Intervention
PfSPZ Vaccine
Normal Saline
Sponsored by
Sanaria Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria focused on measuring Plasmodium falciparum, PfSPZ Vaccine

Eligibility Criteria

1 Year - 12 Years (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Centre de Recherches Médicales de Lambaréné (CERMEL)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Group 1- PfSPZ-Vaccine

Group 2

Group 3

Group 4

Group 5

Group 6

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
The occurrence and frequency of adverse events (AEs)
The occurrence and frequency of Grade 3 solicited adverse AEs (related or unrelated) after vaccination
The occurrence and frequency of AEs
The occurrence and frequency of Grade 3 unsolicited adverse AEs (related or unrelated) after vaccination
The occurrence and frequency of serious adverse events (SAEs)
The occurrence and frequency of SAEs (related or unrelated) after vaccination

Secondary Outcome Measures

The occurrence of all related solicited AE
The occurrence of all related solicited AE after vaccination
The occurrence of all related unsolicited AEs
The occurrence of all related unsolicited AE after vaccination

Full Information

First Posted
April 26, 2018
Last Updated
October 6, 2021
Sponsor
Sanaria Inc.
Collaborators
Centre de Recherches Médicales de Lambaréné (CERMEL), German Center for Infection Research
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1. Study Identification

Unique Protocol Identification Number
NCT03521973
Brief Title
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

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
June 14, 2018 (Actual)
Primary Completion Date
May 18, 2021 (Actual)
Study Completion Date
August 3, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanaria Inc.
Collaborators
Centre de Recherches Médicales de Lambaréné (CERMEL), German Center for Infection Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Plasmodium falciparum, PfSPZ Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1- PfSPZ-Vaccine
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Group 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 4
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Group 5
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 6
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
PfSPZ Vaccine
Intervention Description
Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)
Intervention Type
Other
Intervention Name(s)
Normal Saline
Other Intervention Name(s)
NS
Intervention Description
0.9% Sodium chloride
Primary Outcome Measure Information:
Title
Proportion of volunteers who become parasitemic will be recorded, detected by Thick Blood Smear (TBS) microscopy
Description
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.
Time Frame
From 2 weeks to 6 months after the third PfSPZ Vaccine immunization
Title
Proportion of volunteers who become parasitemic with temperature ≥37.5°C or history of fever
Description
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.
Time Frame
From 2 weeks to 6 months after the third PfSPZ Vaccine immunization
Title
The occurrence and frequency of adverse events (AEs)
Description
The occurrence and frequency of Grade 3 solicited adverse AEs (related or unrelated) after vaccination
Time Frame
From the time of each PfSPZ Vaccine immunization until 7 days after each dose
Title
The occurrence and frequency of AEs
Description
The occurrence and frequency of Grade 3 unsolicited adverse AEs (related or unrelated) after vaccination
Time Frame
From the time of first PfSPZ Vaccine immunization until 28 days after the last dose
Title
The occurrence and frequency of serious adverse events (SAEs)
Description
The occurrence and frequency of SAEs (related or unrelated) after vaccination
Time Frame
Around 27 months (from day of first immunization through study completion)
Secondary Outcome Measure Information:
Title
The occurrence of all related solicited AE
Description
The occurrence of all related solicited AE after vaccination
Time Frame
From the time of each PfSPZ Vaccine immunization until 7 days after each dose
Title
The occurrence of all related unsolicited AEs
Description
The occurrence of all related unsolicited AE after vaccination
Time Frame
From the time of first PfSPZ Vaccine immunization until 28 days after the last dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Selidji Agnandji, MD
Organizational Affiliation
Centre de Recherches Médicales de Lambaréné (CERMEL)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre de Recherches Médicales de Lambaréné (CERMEL)
City
Lambaréné
State/Province
Moyen-Ogooué
Country
Gabon

12. IPD Sharing Statement

Learn more about this trial

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

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