Blood-Stage Plasmodium Vivax Cell Bank

Malaria Clinical Trial

Official title: Induced Blood-Stage Plasmodium Vivax Infection With HMPBS02-Pv Challenge Agent in Healthy Malaria-Naive Adults to Produce a Plasmodium Vivax Parasite Cell Bank for Future Studies

Status Completed

Clinical Trial Summary

Background:

Malaria is caused by a parasite (a type of germ called P. vivax) that is carried by mosquitoes. The disease is transmitted to people when they are bitten by infected mosquitoes. To make drugs and vaccines for malaria, researchers need malaria-infected blood. Plasmodium vivax cell cultures are currently not cultured in vivo, and thus establishing a blood bank from P. vivax infections will be vital for future research.

Objective:

The goal of this study is to infect people with early-stage malaria, then collect infected blood samples to store in a cell bank for future use.

Eligibility:

Healthy adults ages 18-50 who will not be living alone during the study period.

Design:

Participants will be screened with a physical exam, heart health test, and medical history. They will have blood and urine tests. They will take a mental health survey. They must pass an exam to prove they understand the study.

Participants will have red blood cells infected with P. vivax injected into an arm vein. They will be observed for side effects. They will get a thermometer to measure their temperature at home.

For the next 3 days, they will be monitored via phone call or text. Starting on day 4 after the infection, they will have daily study visits to give blood samples. They will likely develop symptoms of malaria, such as fever, chills, headache, and muscle pain.

Participants will be admitted to the hospital for 2-3 days when either they develop symptoms or the daily blood tests detect a certain amount of parasites. Once malaria is confirmed, a sample of their blood will be collected for the cell bank. Then they will be treated for malaria with oral medication that will cure the infection. Those who do not develop malaria will begin treatment after 15 days.

Participants will have follow-up visits 28 and 90 days after infection.

Participation will last for 3-5 months.

Clinical Trial Description

This is a single-center, open-label study using induced blood-stage malaria (IBSM) to produce a human malaria parasite (HMP) bank for use in future studies. This study will be conducted in up to two participants. Participants will be inoculated intravenously (IV) with human malaria parasite blood stage P. vivax (HMPBS02-Pv) parasite-infected erythrocytes (day 0) and then monitored closely via outpatient clinic visits, phone visits, and while inpatient at the NIH Clinical Center (CC) for symptoms and signs of malaria to characterize the safety, tolerability, and infectivity in healthy malaria-naive participants inoculated with P. vivax. Blood sampling will be done periodically to measure parasitemia via quantitative polymerase chain reaction (qPCR) targeting the P. vivax 18S rRNA gene.

The threshold for the commencement of collection of blood for production of the HMP bank and subsequent antimalarial rescue treatment with artemether/lumefantrine will occur when the Malaria Clinical Score is >6 (admission within 24 hours of notification), or parasitemia is >20,000 parasites/mL, or at the investigator s discretion. When this threshold is reached, the participant will be admitted to the NIH CC for further safety assessments before undergoing the blood collection procedure.

After blood collection, the first dose of artemether/lumefantrine will be administered and the participant will remain inpatient for 48-72 hours to monitor for safety and tolerability of rescue therapy, and to ensure adequate clinical and parasitological response to treatment. In the unlikely and unprecedented event that artemether/lumefantrine fails to clear parasitemia, participants will be treated with chloroquine. If oral administration of either artemether/lumefantrine or chloroquine is not possible (e.g., the participant is vomiting), the participant will receive IV treatment with artesunate. After discharge, participants will be followed on an outpatient basis for monitoring of safety and parasite clearance. Follow-up for safety assessments will be performed on day 28 plus or minus 3, day 56 plus or minus 7 (phone call only), and day 90 plus or minus 7 (End of Study).

Participants may also be evaluated for the presence of sexual parasite stages (gametocytes) and other parasite lifecycle stages in the blood during the study using quantitative reverse transcriptase PCR (qRT-PCR).

Objectives: Primary Objective: The collection of blood from healthy participants experimentally infected with P. vivax isolate HMPBS02-Pv for the production of a P. vivax blood-stage parasite bank for use in future studies.

Secondary Objective: To assess the safety and tolerability of the P.vivax IBSM model following inoculation of healthy malaria-naive participants with P. vivax.

Exploratory Objective: To further characterize blood- and sexual stage parasite growth profiles following inoculation with P. vivax isolate and treatment with artemether/lumefantrine.

Endpoints: Primary Endpoint: Collection of blood for the production of a P.vivax blood-stage parasite bank from study participants following experimental infection with P. vivax isolate HMPBS02-Pv.

Secondary Endpoint: Occurrence of solicited and unsolicited adverse events (AEs) following P. vivax inoculation prior to the initiation of antimalarial treatment.

Exploratory Endpoint: The rate of growth of blood- and sexual-stage P. vivax isolate following inoculation and treatment with artemether/lumefantrine as determined by blood smear and/or qPCR. ;

Related Conditions & MeSH terms

• Malaria

• NCT number: NCT05095272
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: February 15, 2022
• Completion date: September 15, 2022