Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1

NCT04201431 | Completed Phase 1 Results DMC

• 1 other identifier: VAC079
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is an Open label, first-in-human, Phase I/IIa, blood-stage P. vivax malaria vaccine trial to assess the safety, immunogenicity and efficacy of the blood-stage Plasmodium vivax malaria vaccine candidate PvDBPII in Matrix M1 in healthy adults living in the UK.

Conditions

Malaria, Vivax

Keywords

PvDBPII

Outcome Measures

Primary Outcomes (2)

• Safety of the PvDBPII-Matrix M1 Vaccine Candidate, Assessed Through Collection of Data on the Frequency, Duration and Severity of Solicited and Unsolicited Adverse Events.

  Number of volunteers reporting a grade 3 solicited or unsolicited adverse event within 28 days post-vaccination or serious adverse event throughout the study period

  12 months

• Establish Whether the PvDBPII-Matrix M1 Vaccine Can Demonstrate a Reduced Parasite Multiplication Rate in Vaccinated Subjects Compared to Infectivity Controls in a Blood-stage Controlled Human Malaria Infection Model

  Assessed by quantitative PCR-derived parasite multiplication rate (PMR). The PMR of the volunteers vaccinated with PvDBPII-Matrix M1 will be compared to the PMR of the malaria-naïve controls partaking in parallel primary CHMI in study VAC069.

  12 months

Secondary Outcomes (4)

• Assessment of the Humoral Immunogenicity of the PvDBPII-Matrix M1 Vaccine Candidate.

  12 months

• Assessment of the Cellular Immunogenicity of the PvDBPII-Matrix M1 Vaccine Candidate.

  12 months

• Immunological Readouts for Association With a Reduced Parasite Multiplication Rate

  12 months

• Assess the Durability of Any Reduction in PMR in Group 3 Volunteers Undergoing a Fourth Vaccination and Rechallenge

  12 months

Study Arms (3)

Group 1

EXPERIMENTAL

Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.

Biological: PvDBPII/Matrix-M1

Group 2

EXPERIMENTAL

If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.

Biological: PvDBPII/Matrix-M1

Group 3

EXPERIMENTAL

Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.

Biological: PvDBPII/Matrix-M1

Interventions

PvDBPII/Matrix-M1 BIOLOGICAL

50ug PvDBPII in 50ug Matrix M1

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult aged 18 to 45 years.
• Red blood cells positive for the Duffy antigen/chemokine receptor (DARC).
• Normal serum levels of Glucose-6-phosphate dehydrogenase (G6PD).
• Negative haemoglobinopathy screen
• 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 highly effective contraception\* for the duration of the study
• Agreement to permanently refrain from blood donation
• 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-malarial regimen following CHMI.
• Willing to reside in Oxford for the post-challenge period, until antimalarials have been completed.
• Answer all questions on the informed consent quiz correctly at first or second attempt
• Female volunteers are required to use a highly effective form of contraception during the course of the study as malaria challenge could pose a serious risk to both maternal health and the unborn foetus.

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).
• Use of anti-malarials within 30 days of CHMI
• Weight less than 50kg, as measured at the screening visit
• Receipt of immunoglobulins within the three months prior to planned administration of the vaccine candidate.
• Receipt of blood products (e.g., blood transfusion) at any time in the past.
• Peripheral venous access unlikely to allow twice daily blood testing (as determined by the Investigator).
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
• Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days preceding or following each study vaccination, with the exception of licensed COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination
• Planned receipt of a COVID-19 vaccine between 2 weeks before the day of CHMI until completion of antimalarial treatment
• Concurrent involvement in another clinical trial or planned involvement 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 any component of the vaccine e.g. egg products, Kathon

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

CCVTM, University of Oxford, Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Hou MM, Barrett JR, Themistocleous Y, Rawlinson TA, Diouf A, Martinez FJ, Nielsen CM, Lias AM, King LDW, Edwards NJ, Greenwood NM, Kingham L, Poulton ID, Khozoee B, Goh C, Mac Lochlainn DJ, Salkeld J, Guilotte-Blisnick M, Huon C, Mohring F, Reimer JM, Chauhan VS, Mukherjee P, Biswas S, Taylor IJ, Lawrie AM, Cho JS, Nugent FL, Long CA, Moon RW, Miura K, Silk SE, Chitnis CE, Minassian AM, Draper SJ. Impact of a blood-stage vaccine on Plasmodium vivax malaria. medRxiv [Preprint]. 2022 May 30:2022.05.27.22275375. doi: 10.1101/2022.05.27.22275375.

  PMID: 35664997 DERIVED

MeSH Terms

Conditions

Malaria, Vivax

Interventions

Matrix-M

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Angela Minassian
• Organization: University of Oxford

angela.minassian@ndm.ox.ac.uk

01865611425

Study Officials

• Angela M Minassian, Dr

  Jenner Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Group 2 is optional to be added only if fewer than 8 volunteers complete in Group 1. Up to 6 volunteers from Group 1 will be invited to join Group 3.

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: December 17, 2019
• Study Start: January 24, 2020
• Primary Completion: July 14, 2022
• Study Completion: July 14, 2022
• Last Updated: November 25, 2024
• Results First Posted: November 25, 2024

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)