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

NCT06607003 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001970001970-I
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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....

Conditions

Malaria

Keywords

IBSM; Challenge; inoculation; Parasitemia; Mosquito Feeding Assay; Malaria Transmission

Outcome Measures

Primary Outcomes (1)

• To assess the safety of the P. vivax IBSM model following inoculation of healthy participants.

  Incidence and severity of local and systemic AEs or SAEs.

  Time of inoculation with the challenge agent until at least 21 days after inpatient discharge

Secondary Outcomes (3)

• To establish a dataset that may be used as a historical control in future interventional IBSM studies.

  From the time of inpatient admission to the time of discharge.

• To evaluate transmission of P. vivax to vector mosquitoes in the IBSM model by mosquito feeding assays.

  From the time of inpatient admission to the time of discharge.

• To establish an appropriate challenge agent dose for use in P. vivax IBSM studies.

  From the time of inoculation until the time of inpatient admission. Expected to be approximately day 9.

Study Arms (2)

P. vivax challenge agent derived from PvHMB-CCE001 Main Arm

EXPERIMENTAL

Up to 50 participants will undergo IBSM to further establish safety of the P. vivax challenge agent derived from PvHMB-CCE001 and evaluate transmission to mosquitoes using feeding assays and assess the host response to P. vivax infection.

Biological: P. vivax challenge agent derived from PvHMB-CCE001

P. vivax challenge agent derived from PvHMB-CCE001 Pilot Arm

EXPERIMENTAL

2 participants will undergo IBSM to establish the safety and infectivity of the P. vivax challenge agent derived from PvHMB-CCE001.

Biological: P. vivax challenge agent derived from PvHMB-CCE001

Interventions

P. vivax challenge agent derived from PvHMB-CCE001 BIOLOGICAL

P. vivax challenge agent derived from PvHMB-CCE001 consists of infected and uninfected erythrocytes stabilized in glycerolyte. Challenge agent derived from this bank consists of thawed, washed, infected and uninfected erythrocytes suspended in injectable-grade normal saline.

P. vivax challenge agent derived from PvHMB-CCE001 Main Arm; P. vivax challenge agent derived from PvHMB-CCE001 Pilot Arm

Eligibility Criteria

• Age: 18 Years - 54 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All of the following criteria must be fulfilled for a participant to undergo IBSM:
• Age \>=18 and \<=54 years.
• RBCs positive for Duffy antigen/chemokine receptor.
• Malaria comprehension exam passed prior to study activities.
• Suitable accommodation and reliable access to the NIHCC for the duration of the study in the opinion of the investigator.
• Persons of childbearing potential must be willing to use reliable contraception from 28 days prior to challenge agent administration to the end of study.
• Signing of the informed consent form.
• Agreement to not live alone from challenge agent administration until the completion of antimalarial treatment.
• Agreement to long-term storage of study samples for future research.

You may not qualify if:

• A participant will be excluded from participating in this trial if any 1 of the following criteria is fulfilled:
• Planned travel to a P. vivax-endemic area during the study period (see https://www.cdc.gov/malaria/travelers/country\_table/a.html).
• History of travel to or residence in a P. vivax malaria-endemic region for more than 2 weeks during the past 2 years.
• Prior confirmed P. vivax malaria diagnosis or clinical history consistent with likely P. vivax infection. At the investigator's discretion, participants may be enrolled if the exposure was remote, e.g., \> 5 years ago.
• Poor peripheral venous access, at the discretion of the investigator.
• For persons of childbearing potential:
• Currently pregnant or breastfeeding, or planning on becoming pregnant or breastfeeding until the end of study.
• Rh blood group negative.
• Being a current or former study team member or clinical trial staff with direct involvement of the trial, or being an employee supervised by a study team member.
• Unwillingness to defer blood donations for at least 3 years.
• Use of any of the following within the specified periods:
• Investigational P. vivax vaccine within the last 2 years.
• Malaria chemoprophylaxis within 3 months of Day 0.
• Chronic systemic immunosuppressive medications (\>14 days) within 6 months (e.g., cytotoxic medications, adrenocorticotrophic hormone, or oral/parental corticosteroids equivalent to \>0.5 mg/kg/day of prednisone). Corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are allowed.
• Prior receipt of packed red cells or other blood products or immunoglobulins within the previous 6 months.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Malaria; Parasitemia

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Joel A Goldberg, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joel A Goldberg, M.D.

CONTACT

(240) 292-4138; joel.goldberg@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: September 23, 2024
• Study Start: November 26, 2024
• Primary Completion (Estimated): November 26, 2027
• Study Completion (Estimated): November 26, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-02-26

Locations

US (1)