Ignite Creation Date:
2025-12-24 @ 7:37 PM
Ignite Modification Date:
2026-01-03 @ 8:06 PM
Study NCT ID:
NCT06607003
Status:
RECRUITING
Last Update Posted:
2025-12-17
First Post:
2024-09-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
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:
National Institute of Allergy and Infectious Diseases (NIAID)
Organization:
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:
RECRUITING
Status Verified Date:
2025-07-30
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
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 627,000 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 627,000 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-CCE001 and 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 host responses to P. vivax IBSM.
* To optimize mosquito infectivity in feeding assays, and study human to mosquito transmission and generate mosquito stages of the parasite.
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 and/or 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) and/or microscopy.
* Antibody responses: Antibody levels elicited following IBSM as measured by enzyme-linked immunosorbent assay (ELISA) (e.g., antibodies against Pvs230, Pvs25, Pvs44/45 sexual stage antigens, or PvMSP3, MSP9, and AMA1 asexual stage antigens), cellular responses, biomarkers, 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-CCE001 and 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 host responses to P. vivax IBSM.
* To optimize mosquito infectivity in feeding assays, and study human to mosquito transmission and generate mosquito stages of the parasite.
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 and/or 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) and/or microscopy.
* Antibody responses: Antibody levels elicited following IBSM as measured by enzyme-linked immunosorbent assay (ELISA) (e.g., antibodies against Pvs230, Pvs25, Pvs44/45 sexual stage antigens, or PvMSP3, MSP9, and AMA1 asexual stage antigens), cellular responses, biomarkers, 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?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 001970-I | None | None | View |