A Controlled Human Vivax Malaria Infection Study Through Inoculation of Infected Erythrocytes

NCT05071079 | Recruiting DMC

• 1 other identifier: MAL21001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to assess the safety and feasibility of blood-stage controlled human P. vivax malaria infection (CHMI) in healthy adult Thai volunteers through experimental injection of cryopreserved P. vivax infected erythrocytes, and to choose the optimal inoculation dose for future P. vivax CHMI studies. In this study, blood-stage CHMI will be conducted in 8 volunteers per inoculum stock who will each be infected with P. vivax by experimental injection with cryopreserved P. vivax infected erythrocytes, which were collected from the controlled human Plasmodium vivax malaria infection model through experimental sporozoite infection in Thai adults (NCT04083508) . There are currently 4 stocks of inocula from 6 volunteers in the NCT04083508 study, which have differing quantities and stages of parasites. The total number of volunteers of this study will be up to 48 (8 volunteers per inocula stock). The volunteers will be monitored closely as in-patients in the Hospital for Tropical Diseases, and will be treated according to the Research Proposal. This study is funded by the UK Wellcome Trust. The grant reference number are Oxford/MORU: 212336/Z/18/Z and 212336/Z/18/A, and Mahidol University: 212336/A/18/Z and 212336/A/18/A.

Conditions

Plasmodium Vivax Infection

Keywords

controlled human malaria infection; Plasmodium Vivax Infection

Outcome Measures

Primary Outcomes (3)

• Incident of treatment-emergent adverse events of blood-stage controlled human P. vivax malaria infection

  Measured by (serious) adverse event (AE) occurrences

  Through study completion, over one year

• Choosing the optimal inoculation dose for future P. vivax CHMI studies, which will be the lowest concentration that produces a reliable infection within a comparable timeframe as compare to the highest concentration.

  The optimal inoculation dose for future P. vivax CHMI studies, which will be the lowest concentration that produces a reliable infection within a comparable timeframe as compare to the highest concentration

  Through study completion, over one year

• Feasibility of primary P. vivax blood-stage CHMI, as measured by successful infection (development of detectable persistent parasitaemia by thick blood film +/- clinical symptoms)

  Through study completion, over one year

Secondary Outcomes (4)

• Geometric mean and standard deviation/error of Pvs25 gene transcript copy number/microL at each time point

  Challenge day; day 1 to 5 or up to day of treatment and during subsequent days of follow-up through study completion, over one year

• Transmissibility of gametocytes from the infected volunteer to Anopheles mosquito vector

  Through study completion, over one year

• Cellular Immune response to primary P. vivax infection (frequencies, percentages (%), and expression level of mononuclear cells)

  Day-1, Day 2, Day 5, Day of blood donation, DayRx7, DayRx28, DayRx90, DayRx1 year

• Level of antibodies and cytokines responses to primary P. vivax infection during different phase of infection

  Day-1, Day 2, Day 5, Day of blood donation, DayRx7, DayRx28, DayRx90, DayRx1 year

Study Arms (4)

Challenge with whole dose blood-stage inoculum (neat)

EXPERIMENTAL

Whole dose: one whole vial, containing approximately 0.5 mL of red blood cells, will be reconstituted in 0.9% saline, to a total volume of 5 mL

Biological: An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculum

Challenge with 1:5 dilution blood-stage inoculum

EXPERIMENTAL

1:5 dilution: one fifth of a vial (containing approximately 0.1 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL.

Biological: An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum

Challenge with 1:10 dilution blood-stage inoculum

EXPERIMENTAL

1:10 dilution: one tenth of a vial (containing approximately 0.05 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL.

Biological: An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum

Challenge with 1:20 dilution blood-stage inoculum

EXPERIMENTAL

1:20 dilution: one twenties of a vial (containing approximately 0.025 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL.

Biological: An inoculum of malaria parasitised red blood cells with 1:20 dilution blood-stage inoculum

Interventions

An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculum BIOLOGICAL

An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with whole dose blood-stage inoculum (neat)

Challenge with whole dose blood-stage inoculum (neat)

An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum BIOLOGICAL

An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:5 dilution blood-stage inoculum

Challenge with 1:5 dilution blood-stage inoculum

An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum BIOLOGICAL

An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:10 dilution blood-stage inoculum

Challenge with 1:10 dilution blood-stage inoculum

An inoculum of malaria parasitised red blood cells with 1:20 dilution blood-stage inoculum BIOLOGICAL

An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:20 dilution blood-stage inoculum

Challenge with 1:20 dilution blood-stage inoculum

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The volunteer must meet all of the following criteria to be eligible for the study:
• Healthy Thai adult aged 20 to 55 years with weight at least 50 kg.
• Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
• Women only: Must practice continuous effective contraception for the duration of study period until 3 months post-challenge.
• COVID-19 vaccination at least two doses of COVID-19 vaccines approved by WHO.
• Agreement to refrain from blood donation during the course of the study and for 1 year after the initiation of antimalarial treatment.
• Willing to be admitted in the Hospital for Tropical Diseases for clinical monitoring, until antimalarial treatment is completed and their symptoms are settling.
• Willing to take a curative antimalarial treatment following CHMI.
• Willing to reside in Bangkok and its vicinity for 2 months after malarial treatment initiation.
• Able to read and write in Thai.
• Provide written informed consent to participate in the trial
• Answer all questions on the informed consent quiz correctly
• Educational level: has at least an undergraduate degree

You may not qualify if:

• The volunteer must NOT enter the study if any of the following apply:
• Positive malaria qPCR OR malaria film
• Presence of any medical condition (either physical or psychological) which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition)
• Presence of chronic disease or chronically use of medication
• Use of systemic antibiotics with known antimalarial activity in the 30 days before challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
• Use of immunoglobulins or blood products (e.g. blood transfusion) at any time in the 1 year preceding enrolment
• Receipt of an investigational product, any vaccine in the 30 days preceding enrolment (D0), or planned receipt during the study period
• Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data or the P. vivax parasite as assessed by the Investigator.
• Any confirmed, or suspected immunosuppressive, or immunodeficient state, including HIV infection, asplenia, history of splenectomy, recurrent, severe infections, and chronic infection
• Immunosuppressant medication within the past 6 months preceding enrolment (D0) (inhaled and topical steroids are allowed)
• History of allergic disease or reactions likely to be exacerbated by malaria infection
• Female participant who is pregnant as evidenced by positive beta-human chorionic gonadotropin (β-HCG) test, lactating, or planning pregnancy during the course of the study
• Contraindications to the use of antimalarial treatment (e.g. chloroquine, atovaquone / proguanil or dihydroartemisinin/piperaquine)
• Use of medications known to have a potentially clinically significant interaction with the antimalarial drug that will be used in this study (chloroquine, atovaquone / proguanil or dihydroartemisinin/piperaquine)
• Known existing positive family history in both 1st AND 2nd degree relatives \< 50 years old for cardiac disease

Sponsors & Collaborators

• University of Oxford: lead
• Wellcome Trust: collaborator

Study Sites (1)

Faculty of Tropical Medicine

Bangkok, 10400, Thailand

RECRUITING

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Study Officials

• Nicholas Day, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas Day, MD

CONTACT

+66 (0)2 354 9170; nickd@tropmedres.ac

Jetsumon Sattabongkot Prachumsri, Ph.D

CONTACT

+66 (0)2 354 9100; jetsumon.pra@mahidol.ac.th

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a double-blinded study; volunteers, clinical investigators, and study staff who perform laboratory study endpoint will be blinded to inoculation arm allocation.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Controlled Plasmodium vivax human malaria infection through experimental inoculation of cryopreserved infected erythrocytes in healthy Thai adults, with a randomized double blind design.

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: October 7, 2021
• Study Start: May 23, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)