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Trial to Evaluate the Safety, Immunogenicity and Protective Efficacy of Three or Five Administrations of GAP3KO Sporozoites

NCT03168854 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 26

Last updated 2025-02-24

No results posted yet for this study

Summary

This Phase 1 trial will include 16 subjects who will receive the Genetically-attenuated p52-/p36-/sap1- Plasmodium falciparum Parasites (GAP3KO) vaccine administered by the bite of approximately 200 infected Anopheles stephensi Mosquitoes in a controlled clinical environment and 12 Controlled Human Malaria Infection (CHMI) infectivity controls (six for each of the two CHMIs). Subjects will be observed for adverse events after each GAP3KO administration. Solicited local and systemic Adverse Events (AEs) will be recorded on a memory aid beginning of the day of first vaccine administration and continuing through 28 days after the last administration. During the vaccination phase clinical laboratory evaluations for safety will be performed on venous blood. Unsolicited AEs will be collected from the day of first vaccination through 28 days after last vaccination and serious adverse events (SAEs) will be collected from the day of first GAP3KO administration through the end of study follow-up. Subjects will be monitored for possible breakthrough peripheral parasitemia with qRT-PCR testing. Four weeks after the last GAP3KO administration, all subjects who completed the immunization phase (up to 16) and a group of six malaria-naïve infectivity controls will be challenged on the same day with wild-type Plasmodium falciparum NF54 sporozoites. Approximately twenty-six weeks after that challenge, all of the protected subjects in Arms 1 and 2 (up to 16) and another six malaria-naïve infectivity controls will receive five infectious A. stephensi mosquito bites on the same day using standard CHMI procedures. For subjects in Study Arms 1 and 2 without documented parasitemia additional post-CHMI follow-ups will occur. For subjects in Study Arms 1 and 2 with documented parasitemia after the first CHMI or who are discontinued for other reasons after the first CHMI, and for the infectivity controls, additional follow ups will occur. Serious Adverse Events (SAEs) will be recorded from the day of CHMI through the end of study follow up and clinical laboratory evaluations for safety will be performed on Day 29 and as clinically indicated (all subjects) and, for subjects with documented parasitemia, on the day malaria treatment is initiated and three days after malaria treatment is initiated. The primary objectives are: 1) To assess the safety and reactogenicity of candidate GAP3KO malaria vaccine when administered by the bite of approximately 200 infected mosquitoes on a five dose schedule, with the first four vaccinations given four weeks apart and the fifth vaccination given eight weeks after the fourth vaccination, and on a three dose schedule, with the second vaccination given four weeks after the first vaccination and the third vaccination given eight weeks after the second vaccination, to healthy malaria-naïve adults aged 18 through 50 years , 2) To confirm attenuation of GAP3KO parasites by assessing the occurrence of breakthrough peripheral parasitemia from the time of first GAP3KO administration through 28 days after last GAP3KO administration.

Conditions

  • Plasmodium Falciparum Infection

Interventions

BIOLOGICAL

Genetically-attenuated p52-/p36-/sap1- Plasmodium falciparum parasite (GAP3KO) strain

Genetically attenuated parasite created by triple deletion (GAP3KO) by deleting the P52, P36, and SAP1 genes in the NF54 wild-type (WT) strain of Plasmodium falciparum (Pf p52(-)/p36(-)/sap1(-) GAP).

OTHER

Malaria challenge

Exposure to mosquitoes infected with P. falciparum.

Sponsors & Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)

    lead NIH

Study Design

Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
50 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2017-07-26
Primary Completion
2019-08-16
Completion
2019-08-16
FDA Drug
Yes

Countries

  • United States

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03168854 on ClinicalTrials.gov