VAC071: A Study to Assess Efficacy of the ChAd63/MVA PvDBP Vaccines

NCT04009096 | Completed Phase 2 Results DMC

• 1 other identifier: VAC071
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, Phase IIa, controlled human malaria infection (CHMI) study aimed to assess whether the new vivax malaria vaccines ChAd63 PvDBP and MVA PvDBP can protect against malaria infection. The participants will receive one or two doses of ChAd63 PvDBP followed by one dose of MVA PvDBP 8 weeks later. Approximately 4 weeks after the second vacccination, the volunteers will be challenged (deliberately infected) with malaria by intravenous injection blood-stage

Conditions

Malaria, Vivax

Keywords

PvDBP; efficacy

Outcome Measures

Primary Outcomes (1)

• Efficacy of the ChAd63 and MVA PvDBP Vaccines, Administered in a Heterologous Prime-boost Regimen, Assessed by a Reduced Parasite Multiplication Rate in Vaccinated Subjects

  Quantitative PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint and a comparison of the endpoint between Groups 1, 2 and 3 (pooled data) and malaria-naïve controls partaking in simultaneous CHMI, under identical conditions, will constitute the primary analysis for efficacy.

  3 months post CHMI

Secondary Outcomes (4)

• Safety of the ChAd63 and MVA PvDBP Vaccines Andidates, Administered in a Heterologous Prime-boost Regimen in a CHMI Study in Healthy Volunteers

  Within 28 days following each vaccination. Vaccinations occurred at 0 and 2 months in Groups 1 and 3 (ChAd63, MVA PvDBP); and at 0, 17 and 19 months in Group 2 (ChAd63, ChAd63, MVA PvDBP).

• The Humoral Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen

  14 days after the final vaccination. Final vaccinations (MVA PvDBP) occurred at 2 months in Groups 1 and 3; and at 19 months in Group 2.

• The Cellular Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen

  14 days after the final vaccination. Final vaccinations (MVA PvDBP) occurred at 2 months in Groups 1 and 3 ; and at 19 months in Group 2.

• Immunological Readouts for Association With a Reduced Parasite Multiplication Rate

  3 months post CHMI

Study Arms (3)

Group 1

EXPERIMENTAL

3 volunteers receiving 5 x 10\^10 vp ChAd63 PvDBP and 2 x 10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.

Biological: ChAd63 PvDBP and MVA PvDBP

Group 2

EXPERIMENTAL

Up to 10 volunteers receiving one dose of 5 x 10\^10 vp ChAd63 PvDBP, 12-18 months later receiving a second dose of 5 x 10\^10 vp ChAd63 PvDBP and 8 weeks later 2 x 10\^8 pfu MVA PvDBP, followed by blood-stage CHMI 2-4 weeks later.

Biological: ChAd63 PvDBP and MVA PvDBP

Group 3

EXPERIMENTAL

If fewer than 6 volunteers complete the study in Group 2, then new volunteers will be recruited into Group 3, to make up a total of 6 volunteers between Groups 2 and 3 who complete all vaccinations and CHMI. Volunteers in Group 3 will receive 5 x 10\^10 vp ChAd63 PvDBP and 2 x10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.

Biological: ChAd63 PvDBP and MVA PvDBP

Interventions

ChAd63 PvDBP and MVA PvDBP BIOLOGICAL

one dose of 5 x 10\^10 vp ChAd63 PvDBP and one dose of 2 x 10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen.

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).
• 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 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 duration of the study, until antimalarials have been completed.
• Answer all questions on the informed consent quiz correctly.
• Female volunteers are required to use an 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.
• Current or planned treatment with long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Chronic use of antibiotics with antimalarial effects (e.g. tetracyclines for dermatologic patients, trimethoprim-sulfamethoxazole for recurrent urinary tract infections, etc.).
• 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 within 14 days before or 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.
• History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
• 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).

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Centre for Clinical Vaccinology & Tropical Medicine

Oxford, Oxfordshire, 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

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, MBBS MA DPhil MRCP FRCPath

  University of Oxford

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 5, 2019
• Study Start: July 18, 2019
• Primary Completion: July 7, 2022
• Study Completion: July 7, 2022
• Last Updated: April 12, 2024
• Results First Posted: April 12, 2024

Record last verified: 2022-09

Locations

GB (1)