Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

This Phase 1 trial will include 16 subjects in Study Arms 1 and 2 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 for at least 60 minutes 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 (six months) 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. The secondary objectives are: 1) To assess the efficacy of GAP3KO vaccine given on a five dose schedule and GAP3KO vaccine given on a three dose schedule against malaria challenge four weeks after last vaccination, and re-challenge 26 weeks (six months) after the first challenge, using standard controlled human malaria infection (CHMI) procedures, 2) To assess humoral and cell-mediated immune responses to malaria antigens induced by GAP3KO administration and by CHMI. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03168854
Study type Interventional
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact
Status Completed
Phase Phase 1
Start date July 26, 2017
Completion date August 16, 2019

See also
  Status Clinical Trial Phase
Recruiting NCT05400655 - Anti-malaria MAb in Kenyan Children Phase 2
Completed NCT02773979 - PfSPZ Challenge in Healthy Malaria-Naïve Adults in the United States Phase 1
Completed NCT03660839 - Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria Phase 2
Terminated NCT00988507 - Dose Ranging Study of Ferroquine With Artesunate in African Adults and Children With Uncomplicated Plasmodium Falciparum Malaria Phase 2
Recruiting NCT05750459 - Pharmacokinetic Study of IV Artesunate to Treat Children With Severe Malaria Phase 4
Completed NCT02020330 - Optimising Operational Use of Artemether-lumefantrine Comparing 3 Day Versus 5 Day Phase 3
Completed NCT05816330 - L9LS MAb in Malian Adults Phase 2
Completed NCT02353494 - Efficacy and Safety of Dihydroartemisinin-piperaquine (DHP) for the Treatment of Uncomplicated Malaria N/A
Completed NCT00744133 - Malaria Challenge With NF54 Strain Phase 1
Active, not recruiting NCT05304611 - Anti-malaria MAb in Malian Children Phase 2
Completed NCT03014258 - A Systems Biology Approach to Malaria Immunity Phase 1
Terminated NCT02497612 - To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine and Artefenomel in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria Phase 2
Completed NCT00371189 - Adenovirus Vaccine for Malaria Phase 1
Not yet recruiting NCT05025761 - Reducing Malaria Transmission in Forest-going Mobile and Migrant Populations in Myanmar N/A
Completed NCT00379821 - Chloroquine Alone or in Combination for Malaria in Children in Malawi Phase 3
Completed NCT04329104 - Safety and Efficacy of CIS43LS Anti-malaria mAb in Mali Phase 2
Completed NCT03589794 - rCSP/AP10-602 [GLA-LSQ] Vaccine Trial Phase 1
Completed NCT02780154 - PfSPZ Challenge in Non-immune Adults in Baltimore, USA Phase 1
Completed NCT02143934 - Effect of Liver and Blood-stage Treatment on Subsequent Plasmodium Reinfection and Morbidity Phase 4
Completed NCT02663700 - Safety and Immunogenicity of Sanaria's Irradiated Sporozoite Vaccine (PfSPZ Vaccine) in Malaria-Experienced Adults in Burkina Faso Phase 1