NCT03797989

VAC069: A Study of Blood-stage Controlled Human P. Vivax Infection

Completed EARLY_PHASE1 Results posted Last updated 25 April 2025

What this trial tests

EARLY_PHASE1 trial testing P. vivax infected inoculum (parasitised red blood cells) in Malaria, Vivax in 19 participants. Completed in 20 December 2022.

Timeline

10 January 2019

Primary endpoint
20 December 2022

20 December 2022

Quick facts

Lead sponsor	University of Oxford
Phase	EARLY_PHASE1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	other
Enrollment	19
Start date	10 January 2019
Primary completion	20 December 2022
Estimated completion	20 December 2022
Sites	1 location across United Kingdom

Drugs / interventions tested

• P. vivax infected inoculum (parasitised red blood cells) — full drug profile →

Conditions studied

• Malaria, Vivax — all drugs for Malaria, Vivax →

Sponsor

University of Oxford

Who can join

Adults 18 to 50, any sex, with Malaria, Vivax. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Serious Adverse Events Primary · 36 months

Group	Value	95% CI
Primary P. Vivax CHMI	1

Number of Participants Who Developed Infection/Reached Diagnosis Criteria, Used to Select the Optimal Inoculation Dose to Take Forward to Future P. Vivax CHMI Studies Based on a Protocol-specified Algorithm Primary · 3 months

Choosing the optimal inoculation dose to take forward to future P. vivax CHMI studies will be decided based on the following algorithm: Ideal choice = the first group (2/2 volunteers) to reach diagnosis criteria (within 21 days). N.B. If both volunteers in Group 1 develop infection AND both volunteers in Group 2 (or 3) reliably develop infection within 5 days of Group 1 (and within the 21-day window) then the lowest dose group should be chosen.

Group	Value	95% CI
Phase A: Group 1	2
Phase A: Group 2	2
Phase A: Group 3	2

Feasibility of Primary P. Vivax Blood-stage CHMI as Measured by Successful Infection (Development of Detectable Persistent Parasitaemia by Thick Film and qPCR +/- Clinical Symptoms) Primary · 36 months

Number of participants developing detectablable parasitaemia during primary CHMI with P. vivax (PvW1 clone)

Group	Value	95% CI
Primary P. Vivax CHMI	19

Safety of Secondary and Tertiary P. Vivax Controlled Blood-stage CHMI as Measured by (S)AE Occurrences Secondary · 36 months

Group	Value	95% CI
Secondary P. Vivax CHMI	0
Tertiary P. Vivax CHMI	0
VAC069E - P. Falciparum CHMI	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from day of malaria challenge (CHMI) until 3 months after each challenge.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Primary P. Vivax CHMI

Serious: 1/19 (5%)

Deaths: 0/19

Secondary P. Vivax CHMI

Serious: 0/12 (0%)

Deaths: 0/12

Tertiary P. Vivax CHMI

Serious: 0/2 (0%)

Deaths: 0/2

VAC069E - P. Falciparum CHMI

Serious: 0/6 (0%)

Deaths: 0/6

Serious adverse events (1 terms)

Reaction	System	Primary P. Vivax CHMI	Secondary P. Vivax CHMI	Tertiary P. Vivax CHMI	VAC069E - P. Falciparum CHMI
Upper limb fracture	Musculoskeletal and connective tissue disorders	—	—	—	—

Other adverse events (15 terms — click to expand)

Reaction	System	Primary P. Vivax CHMI	Secondary P. Vivax CHMI	Tertiary P. Vivax CHMI	VAC069E - P. Falciparum CHMI
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Tooth infection	Gastrointestinal disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Tonsillitis	Infections and infestations	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—
Stress	Psychiatric disorders	—	—	—	—
Dry throat	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—

Most-reported serious reactions: Upper limb fracture.

Data from ClinicalTrials.gov NCT03797989 adverse events section.

Sponsor's own description

This is a clinical study to assess the safety and feasibility of Plasmodium vivax (P. vivax) controlled blood-stage human malaria infection (CHMI), by inoculation using a newly created source of P. vivax malaria-infected blood.

25 healthy malaria-naïve UK volunteers, aged 18 - 50, will be recruited through the five phases of the study at the CCVTM, Oxford. Volunteers will undergo primary, secondary and tertiary P. vivax blood-stage challenges, which will be induced by injection of P. vivax infected blood. After the first challenge, the optimal dose for blood-stage CHMI will be selected and used for the second and third challenges. Through each challenge period, volunteers will have blood taken at regular intervals to measure the parasite growth, quantify the sexual parasite forms and assess the immune response to P. vivax infection. Transmission of P. vivax from volunteers to the Anopheline mosquito vectors will also be assessed.

In each challenge, following diagnosis, volunteers will be treated with a standard antimalarial course of oral artemether-lumefantrine (Riamet), given over 60 hours. Volunteers who take part in this study will be involved in the trial for approximately 2 years, receiving each of the three challenges at intervals of approximately 5 (and up to 9) months. Volunteers will be followed for 3 months after their last challenge.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cell therapies in the clinic.
   Wang LL, Janes ME, Kumbhojkar N, Kapate N, et al · · 2021 · cited 99× · PMID 34027097 · DOI 10.1002/btm2.10214
2. Structural basis for inhibition of Plasmodium vivax invasion by a broadly neutralizing vaccine-induced human antibody.
   Rawlinson TA, Barber NM, Mohring F, Cho JS, et al · · 2019 · cited 58× · PMID 31133755 · DOI 10.1038/s41564-019-0462-1
3. Vaccination with <i>Plasmodium vivax</i> Duffy-binding protein inhibits parasite growth during controlled human malaria infection.
   Hou MM, Barrett JR, Themistocleous Y, Rawlinson TA, et al · · 2023 · cited 31× · PMID 37437014 · DOI 10.1126/scitranslmed.adf1782
4. Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly.
   Minassian AM, Themistocleous Y, Silk SE, Barrett JR, et al · · 2021 · cited 27× · PMID 34609964 · DOI 10.1172/jci.insight.152465
5. Malaria therapeutics: are we close enough?
   Tripathi H, Bhalerao P, Singh S, Arya H, et al · · 2023 · cited 12× · PMID 37060004 · DOI 10.1186/s13071-023-05755-8
6. A systematic analysis of the human immune response to Plasmodium vivax.
   Bach FA, Muñoz Sandoval D, Mazurczyk M, Themistocleous Y, et al · · 2023 · cited 11× · PMID 37616070 · DOI 10.1172/jci152463
7. The challenges of <i>Plasmodium vivax</i> human malaria infection models for vaccine development.
   Roobsoong W, Yadava A, Draper SJ, Minassian AM, et al · · 2022 · cited 6× · PMID 36685545 · DOI 10.3389/fimmu.2022.1006954
8. Plasmodium falciparum infection induces T cell tolerance that is associated with decreased disease severity upon re-infection.
   Muñoz Sandoval D, Bach FA, Ivens A, Harding AC, et al · · 2025 · cited 4× · PMID 40214640 · DOI 10.1084/jem.20241667