Study of Controlled Human Plasmodium Vivax Infection

NCT03377296 | Completed

• 2 other identifiers: VAC068228948
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

This is a sporozoite-challenge clinical study with the primary aim of assessing the safety and feasibility of controlled human P. vivax malaria infection in two healthy volunteers. The investigators will also assess the growth of and the immune response to P. vivax infection, and assess the induction of sexual gametocytaemia post-CHMI via the natural route of malaria infection (mosquito bite). A secondary objective is to develop a blood inoculum of P. vivax-infected blood for future testing of candidate vaccines.

Conditions

Malaria, Vivax

Outcome Measures

Primary Outcomes (5)

• Incidence of (Serious) Adverse Events following P. vivax CHMI

  Safety of P. vivax CHMI, as measured by incidence of (Serious) Adverse Events (Safety and Tolerability)

  Up to 21 days post challenge

• Clinical symptoms of malaria infection post CHMI

  Measure of successful infection (development of clinical symptoms of malaria)

  Up to 21 days post challenge

• Parasitaemia post CHMI

  Measure of successful infection (development of detectable persistent parasitaemia) symptoms).

  Up to 90 days post challenge

• Immune response to P. vivax

  Immune response to P. vivax, as measured by antibody, B cell and T cell responses.

  Up to 90 days post challlenge

• Gametocytaemia

  Gametocytaemia, as measured by qPCR

  Up to 90 days post challenge

Secondary Outcomes (1)

• Collection and freezing down of P. vivax-infected blood.

  Collected between day 8 and day 14 post challenge, determined by symptoms and parasitaemia

Study Arms (1)

Plasmodium Vivax infection

EXPERIMENTAL

Both volunteers will be infected with Plasmodium Vivax (as described below in full in "Interventions"). i.e., there is only one arm to this study.

Other: Plasmodium vivax infection; Procedure: Collection of 250mL blood from each volunteer (N=2)

Interventions

Plasmodium vivax infection OTHER

Two healthy human volunteers are exposed to the bites of five infectious mosquitoes per participant (by placing their forearms over the pot containing mosquitoes) for 5-10 minutes. Fed mosquitoes (as indicated by the presence of a blood meal in the abdomen) are individually dissected and assessed for sporozoite load (graded 0 to +4; a gland rating of +2 or more, representing 10 or more observed sporozoites, qualifies as being infectious). If, by this method the volunteer is found to have been inoculated by less than five infected mosquitoes, further mosquitoes are allowed to feed on the volunteer until a total of 5 appropriately infected mosquitoes have fed. The bite-challenge procedure continues until the subject has been bitten by 5 infectious mosquitoes.

Plasmodium Vivax infection

Collection of 250mL blood from each volunteer (N=2) PROCEDURE

Collection of 250mL of P. vivax-infected blood from each volunteer when a threshold parasitaemia/ symptoms are met

Plasmodium Vivax infection

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult aged 18 to 50 years.
• Blood group O, Rhesus negative.
• Red blood cells positive for the Duffy antigen/chemokine receptor (DARC).
• High metaboliser of primaquine (as determined by CYP2D6 genotype).
• Normal serum levels of Glucose-6-phosphate dehydrogenase (G6PDH).
• Satisfactory serum levels of Primaquine (when administered as test dose).
• Able and willing (in the Investigator's opinion) to comply with all study requirements.
• Willing to allow the Investigators to discuss the volunteer's medical history with their General Practitioner.
• Women only: Must practice continuous effective contraception\* for the duration of the clinic visits (first 3 months post-CHMI).
• Agreement to refrain from blood donation during the course of the study and for at least 5 years after the end of their involvement in the study.
• Written informed consent to participate in the trial.
• Reachable (24/7) by mobile phone during the period between CHMI and completion of all antimalarial treatment.
• Willing to take a curative anti-malaria regimen following CHMI.
• Willing to be admitted to the research bay on the John Warin ward at the Churchill Hospital for blood donation and clinical monitoring, until antimalarial treatment is underway and their symptoms are settling.
• Willing to reside in Oxford for the duration of the study, until all antimalarials have been completed.

You may not qualify if:

• History of clinical malaria (any species).
• Travel to a clearly malaria endemic locality during the study period or within the preceding six months.
• Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
• Blood group A/B and/or Rhesus positive.
• Red blood cells negative for the Duffy antigen/chemokine receptor (DARC).
• Glucose-6-phosphate dehydrogenase (G6PDH) deficient.
• Inadequate serum levels of Primaquine (when administered as test dose).
• Current anaemia (Haemoglobin \< 9 g/dL).
• Use of immunoglobulins or blood products (e.g., blood transfusion) at any time in the past.
• History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
• Venepuncture unlikely to allow a 250 mL blood donation (as determined by the Investigator).
• Receipt of an investigational product in the 30 days preceding enrolment, 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; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
• History of allergic disease or reactions likely to be exacerbated by malaria infection.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (2)

Centre for Clinical Vaccinology & Tropical Medicine

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

John Warin Ward, Oxford University NHS Foundation Trust

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Minassian AM, Themistocleous Y, Silk SE, Barrett JR, Kemp A, Quinkert D, Nielsen CM, Edwards NJ, Rawlinson TA, Ramos Lopez F, Roobsoong W, Ellis KJ, Cho JS, Aunin E, Otto TD, Reid AJ, Bach FA, Labbe GM, Poulton ID, Marini A, Zaric M, Mulatier M, Lopez Ramon R, Baker M, Mitton CH, Sousa JC, Rachaphaew N, Kumpitak C, Maneechai N, Suansomjit C, Piteekan T, Hou MM, Khozoee B, McHugh K, Roberts DJ, Lawrie AM, Blagborough AM, Nugent FL, Taylor IJ, Johnson KJ, Spence PJ, Sattabongkot J, Biswas S, Rayner JC, Draper SJ. Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly. JCI Insight. 2021 Dec 8;6(23):e152465. doi: 10.1172/jci.insight.152465.

  PMID: 34609964 DERIVED

MeSH Terms

Conditions

Malaria, Vivax

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Angela M Minassian

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 19, 2017
• Study Start: March 3, 2018
• Primary Completion: April 13, 2023
• Study Completion: April 13, 2023
• Last Updated: June 29, 2023

Record last verified: 2023-06

Locations

GB (2)