Blood-Stage Plasmodium Vivax Cell Bank

NCT05095272 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 10000212000212-I
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria

Keywords

Malaria; Parasitemia; IBSM; inoculation; Challenge

Outcome Measures

Primary Outcomes (1)

• P. Vivax Blood Collection

  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.

  Time of enrollment until blood collection for blood-stage parasite bank (10-11 days post-infection)

Study Arms (1)

Healthy malaria-naive US adults

EXPERIMENTAL

A single dose of cryopreserved inoculum containing blood-stage P. vivax will be administered IV

Biological: HMPBS02-Pv

Interventions

HMPBS02-Pv BIOLOGICAL

The blood-stage P. vivax master cell bank HMPBS02-Pv was also produced using blood collected from a consenting patient with naturally acquired malaria infection. The malaria infection was confirmed to be P. vivax by species-specific PCR at Pathology Queensland (accredited by the Australian National Association of Testing Authorities) and further confirmed by deep sequencing at the Sanger Institute. The clinical response to antimalarial chemotherapy was also demonstrated with this donor, who was successfully cured with artemether/lumefantrine.

Healthy malaria-naive US adults

Eligibility Criteria

• Age: 18 Years - 50 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 participate in this trial:
• Age \>=18 and \<=50 years.
• In good general health and without clinically significant medical history.
• Does not live alone from study Day 0 until the end of the antimalarial drug treatment.
• Malaria comprehension exam completed, passed (a score of \>=80% or per investigator s discretion) and reviewed prior to enrollment.
• Reliable access to the NIH CC and availability to participate for duration of study.
• Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to study Day 0 to 28 days following IBSM.
• Sign written informed consent prior to undertaking any study-related procedure.

You may not qualify if:

• A participant will be excluded from participating in this trial if any one of the following criteria is fulfilled:
• Currently breastfeeding (if female).
• Pregnant as determined by a positive urine or serum human choriogonadotropin (Beta-hCG) test (if female).
• Planned travel to a malaria-endemic area during the study period and up to 2 weeks following the EOS visit.
• History of recent travel to or residence in a P. vivax malaria-endemic region for more than 2 weeks during the past 5 years.
• Planned travel to a malaria-endemic region during the course of the study (for endemic regions, see www.cdc.gov/malaria/travelers/country\_table).
• Any history of confirmed malaria diagnosis on peripheral blood smear or by clinical history
• Participation in a previous malaria challenge study.
• Screening laboratory parameters outside of local lab normal range, to include serum-corrected calcium, creatinine, hepatic transaminase enzymes (ALT, AST), total bilirubin (unless the participant has documented Gilbert syndrome), and hemoglobin. Participants may be included at the investigator s discretion for not clinically significant values outside of normal range.
• Abnormal urinalysis as defined by positive urine glucose, protein, and hemoglobin. Participant can be included if investigator determine the abnormality is not clinically significant.
• Duffy blood group negative (male or female).
• ABO blood type other than O (male or female).
• Rh blood group negative (females of childbearing potential).
• Anticipated use during the study period, or use within the following periods prior to enrollment of any of the following: Investigational malaria vaccine within the last 2 years; Malaria chemoprophylaxis within the past 6 months; Chronic systemic immunosuppressive medications (\>14 days) within 6 months; Blood products or immunoglobulins within the previous 6 months; Systemic antibiotics or medications with potential antimalarial effects within the past 6 weeks; Investigational or non-registered product or vaccine within 30 days; Receipt of any vaccination within 28 days prior to P. vivax IBSM; Medications known to interact with artemether/lumefantrine; Anticoagulants within the past 28 days.
• History of:

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

Location

Related Publications (3)

• Griffin P, Pasay C, Elliott S, Sekuloski S, Sikulu M, Hugo L, Khoury D, Cromer D, Davenport M, Sattabongkot J, Ivinson K, Ockenhouse C, McCarthy J. Safety and Reproducibility of a Clinical Trial System Using Induced Blood Stage Plasmodium vivax Infection and Its Potential as a Model to Evaluate Malaria Transmission. PLoS Negl Trop Dis. 2016 Dec 8;10(12):e0005139. doi: 10.1371/journal.pntd.0005139. eCollection 2016 Dec.

  PMID: 27930652 BACKGROUND

• McCarthy JS, Griffin PM, Sekuloski S, Bright AT, Rockett R, Looke D, Elliott S, Whiley D, Sloots T, Winzeler EA, Trenholme KR. Experimentally induced blood-stage Plasmodium vivax infection in healthy volunteers. J Infect Dis. 2013 Nov 15;208(10):1688-94. doi: 10.1093/infdis/jit394. Epub 2013 Aug 1.

  PMID: 23908484 BACKGROUND

• Collins KA, Wang CY, Adams M, Mitchell H, Robinson GJ, Rampton M, Elliott S, Odedra A, Khoury D, Ballard E, Shelper TB, Lucantoni L, Avery VM, Chalon S, Moehrle JJ, McCarthy JS. A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions. J Clin Invest. 2020 Jun 1;130(6):2920-2927. doi: 10.1172/JCI134923.

  PMID: 32045385 BACKGROUND

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

Results Point of Contact

• Title: Dr. Patrick E. Duffy; Lab Chief
• Organization: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health

patrick.duffy@nih.gov

240.381.1317

Study Officials

• Patrick E Duffy, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: October 27, 2021
• Study Start: February 15, 2022
• Primary Completion: June 24, 2022
• Study Completion: September 15, 2022
• Last Updated: July 11, 2023
• Results First Posted: July 11, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)