Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06607003
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-20
Brief Title:
Induced Blood-Stage Malaria in Healthy Malaria-Naive Adults to Assess the Safety and Infectivity of Plasmodium Vivax Challenge Agent and Evaluate Transmission in Mosquito Feeding Assays
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Phase 1 Study of Induced Blood-Stage Malaria in Healthy Malaria-Naive Adults to Assess the Safety and Infectivity of Plasmodium Vivax Challenge Agent and Evaluate Transmission in Mosquito Feeding Assays
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09-18
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Malaria is a disease caused by parasites transmitted to people by mosquitoes Around the world there were 241 million cases and 627000 deaths from malaria in 2020 Researchers are working to develop vaccines and treatments for this disease
Objective
To learn how malaria develops in people how the body s immune system reacts to malaria and how malaria spreads from people to mosquitoes
Eligibility
Healthy people in the Washington DC area aged 18 to 54 years They cannot live alone during parts of the study
Design
Participants will be infected with a parasite that causes malaria The parasite will be in donated blood it will be given through an IV
Participants will likely develop symptoms within a week after the injection Researchers will call daily to check on their health After about 6 days participants will come to the NIH clinic each day for blood tests
Participants will check in to the NIH clinic around 10 days after the injection They will stay in the clinic 3 to 6 days They will have multiple blood tests every day
Participants will be bitten by mosquitoes up to 4 times Cups containing mosquitoes will be held against their skin for 15 minutes
Participants will begin taking chloroquine close to the end of their clinic stay Chloroquine is a pill taken by mouth once or twice a day for 3 days It is FDA-approved to treat malaria
Participants will have follow-up visits 1 and 3 weeks after discharge
Malaria is a disease caused by parasites transmitted to people by mosquitoes Around the world there were 241 million cases and 627000 deaths from malaria in 2020 Researchers are working to develop vaccines and treatments for this disease
Objective
To learn how malaria develops in people how the body s immune system reacts to malaria and how malaria spreads from people to mosquitoes
Eligibility
Healthy people in the Washington DC area aged 18 to 54 years They cannot live alone during parts of the study
Design
Participants will be infected with a parasite that causes malaria The parasite will be in donated blood it will be given through an IV
Participants will likely develop symptoms within a week after the injection Researchers will call daily to check on their health After about 6 days participants will come to the NIH clinic each day for blood tests
Participants will check in to the NIH clinic around 10 days after the injection They will stay in the clinic 3 to 6 days They will have multiple blood tests every day
Participants will be bitten by mosquitoes up to 4 times Cups containing mosquitoes will be held against their skin for 15 minutes
Participants will begin taking chloroquine close to the end of their clinic stay Chloroquine is a pill taken by mouth once or twice a day for 3 days It is FDA-approved to treat malaria
Participants will have follow-up visits 1 and 3 weeks after discharge
Detailed Description:
Study Description Single-center open-label phase 1 study to characterize the safety and infectivity of Plasmodium vivax P vivax challenge agent for induced blood-stage malaria IBSM in malaria-naive participants at the NIH Clinical Center NIHCC Challenge agent derived from 2 cell banks of cryopreserved blood-stage P vivax PvHMB-CCE001 and PvHMB-CCE002 will be administered intravenously A minimum of 2 participants per bank will undergo IBSM to establish the safety and infectivity of the challenge agent Additional participants with a ceiling of 16 per bank undergoing IBSM will be enrolled to further develop the model including to evaluate transmission to mosquitoes using feeding assays and assess the host response to P vivax infection All participants who receive challenge agent will undergo antimalarial treatment Qualification of the IBSM model in transmission assays is a requisite goal in supporting future studies of transmission-blocking vaccines TBVs
Challenge agent derived from each of the 2 banks PvHMB-CCE001and PvHMB-CCE002 will be assessed first in a pilot group of at least 2 participants then subsequently in a main group with participants receiving inoculations in cohorts of up to 10 individuals based on logistical considerations including the capacity of clinic resources The dose of the challenge agent may be adjusted if needed to generate reliable IBSM
Objectives
Primary Objective
--To assess the safety of the P vivax IBSM model following inoculation of healthy participants
Secondary Objectives
To establish an appropriate challenge agent dose for use in P vivax IBSM studies
To evaluate transmission of P vivax to vector mosquitoes in the IBSM model by mosquito feeding assays
To establish a dataset that may be used as a historical control in future interventional IBSM transmission studies
Exploratory Objectives
To further characterize blood and sexual stage parasite growth profiles following blood-stage P vivax challenge and treatment
To assess the immune responses to P vivax IBSM
To optimize mosquito infectivity in feeding assays including the generation of mosquito stages of the parasite lifecycle
Endpoints
Primary Endpoint
--Incidence and severity of local and systemic adverse events AEs or serious adverse events SAEs
Secondary Endpoints
A suitable dose of challenge agent that generates parasitemia in a reliable and timely manner as determined by the investigator
Transmission of P vivax to Anopheles spp using mosquito feeding assays including direct feeding assays andor membrane feeding assays as determined by the detection of oocysts following midgut dissection Additional optional measures may include salivary gland dissection or detection by molecular methods
Demonstration of transmission in mosquito feeding assays among a requisite number of participants
Exploratory Endpoints
Asexual blood-stage and sexual stage parasite growth profiles by quantitative polymerase chain reaction qPCR andor microscopy
Antibody responses Antibody levels elicited following IBSM as measured by enzyme-linked immunosorbent assay ELISA eg antibodies against Pvs230 Pvs25 Pvs4445 sexual stage antigens or PvMSP3 MSP9 and AMA1 asexual stage antigens cellular immune responses and transcriptional profiling at various timepoints
Collection of gametocyte-containing blood and study in mosquito transmission assays
Challenge agent derived from each of the 2 banks PvHMB-CCE001and PvHMB-CCE002 will be assessed first in a pilot group of at least 2 participants then subsequently in a main group with participants receiving inoculations in cohorts of up to 10 individuals based on logistical considerations including the capacity of clinic resources The dose of the challenge agent may be adjusted if needed to generate reliable IBSM
Objectives
Primary Objective
--To assess the safety of the P vivax IBSM model following inoculation of healthy participants
Secondary Objectives
To establish an appropriate challenge agent dose for use in P vivax IBSM studies
To evaluate transmission of P vivax to vector mosquitoes in the IBSM model by mosquito feeding assays
To establish a dataset that may be used as a historical control in future interventional IBSM transmission studies
Exploratory Objectives
To further characterize blood and sexual stage parasite growth profiles following blood-stage P vivax challenge and treatment
To assess the immune responses to P vivax IBSM
To optimize mosquito infectivity in feeding assays including the generation of mosquito stages of the parasite lifecycle
Endpoints
Primary Endpoint
--Incidence and severity of local and systemic adverse events AEs or serious adverse events SAEs
Secondary Endpoints
A suitable dose of challenge agent that generates parasitemia in a reliable and timely manner as determined by the investigator
Transmission of P vivax to Anopheles spp using mosquito feeding assays including direct feeding assays andor membrane feeding assays as determined by the detection of oocysts following midgut dissection Additional optional measures may include salivary gland dissection or detection by molecular methods
Demonstration of transmission in mosquito feeding assays among a requisite number of participants
Exploratory Endpoints
Asexual blood-stage and sexual stage parasite growth profiles by quantitative polymerase chain reaction qPCR andor microscopy
Antibody responses Antibody levels elicited following IBSM as measured by enzyme-linked immunosorbent assay ELISA eg antibodies against Pvs230 Pvs25 Pvs4445 sexual stage antigens or PvMSP3 MSP9 and AMA1 asexual stage antigens cellular immune responses and transcriptional profiling at various timepoints
Collection of gametocyte-containing blood and study in mosquito transmission assays
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None