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NCT04009096

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

Completed Phase 2 Results posted Last updated 12 April 2024
What this trial tests

Phase 2 trial testing ChAd63 PvDBP and MVA PvDBP in Malaria, Vivax in 16 participants. Completed in 7 July 2022.

Timeline
18 July 2019
Primary endpoint
7 July 2022
7 July 2022

Quick facts

Lead sponsorUniversity of Oxford
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposeprevention
Enrollment16
Start date18 July 2019
Primary completion7 July 2022
Estimated completion7 July 2022
Sites1 location across United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

University of Oxford

Who can join

Adults 18 to 45, 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.

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 Primary · 3 months post CHMI

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.

GroupValue95% CI
Groups 1, 2 and 3 Volunteers Completing CHMI5.44.0 – 7.3
Safety of the ChAd63 and MVA PvDBP Vaccines Andidates, Administered in a Heterologous Prime-boost Regimen in a CHMI Study in Healthy Volunteers Secondary · 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).

No of participants reporting adverse event

Any grade 3 solicited adverse event
GroupValue95% CI
Following ChAd63 PvDBP Vaccination1
Following MVA PvDBP Vaccination2
Any grade 3 unsolicited adverse event
GroupValue95% CI
Following ChAd63 PvDBP Vaccination0
Following MVA PvDBP Vaccination0
Any grade 3 laboratory adverse event
GroupValue95% CI
Following ChAd63 PvDBP Vaccination1
Following MVA PvDBP Vaccination0
The Humoral Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen Secondary · 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.

Total IgG antibody response to the P. vivax Duffy-binding protein (PvDBP)

GroupValue95% CI
Groups 1, 2 and 3 Volunteers299 – 85
The Cellular Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen Secondary · 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.

PvDBPII-specific CD4+ CD45RA- CCR7- effector memory T cells producing IFN-γ

GroupValue95% CI
Groups 1, 2 and 3 Volunteers0.68250.09500 – 1.951

Adverse events — posted to ClinicalTrials.gov

Time frame: Data on solicited adverse events were collected for 7 days after vaccination and unsolicited adverse events for 28 days post-vaccination. Serious adverse events were collected for the study duration: up to 12 months for Group 1 and 3 participants, and up to 29 months for Group 2 participants.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Following ChAd63 PvDBP Vaccination
Serious: 0/16 (0%)
Deaths: 0/16
Following MVA PvDBP Vaccination
Serious: 0/8 (0%)
Deaths: 0/8
Other adverse events (3 terms — click to expand)

ReactionSystemFollowing ChAd63 PvDBP Vac…Following MVA PvDBP Vaccin…
DysmenorrhoeaReproductive system and breast disorders
FeverishGeneral disorders
FeverGeneral disorders

Data from ClinicalTrials.gov NCT04009096 adverse events section.

Sponsor's own description

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

Publications & conference data

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

  1. 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
  2. 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
  3. Recent Advances in the Development of Adenovirus-Vectored Vaccines for Parasitic Infections.
    Koger-Pease C, Perera DJ, Ndao M. · · 2023 · cited 11× · PMID 36986434 · DOI 10.3390/ph16030334
  4. Analyses of human vaccine-specific circulating and bone marrow-resident B cell populations reveal benefit of delayed vaccine booster dosing with blood-stage malaria antigens.
    Barrett JR, Silk SE, Mkindi CG, Kwiatkowska KM, et al · · 2023 · cited 6× · PMID 38299155 · DOI 10.3389/fimmu.2023.1193079
  5. 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
  6. PvDBPII elicits multiple antibody-mediated mechanisms that reduce growth in a Plasmodium vivax challenge trial.
    Martinez FJ, White M, Guillotte-Blisnick M, Huon C, et al · · 2024 · cited 4× · PMID 38184681 · DOI 10.1038/s41541-023-00796-7
  7. Intravenous injection of a novel viral immunotherapy encoding human interleukin-7 in nonhuman primates is safe and increases absolute lymphocyte count.
    Coupet CA, Dubois C, Evlachev A, Kehrer N, et al · · 2022 · cited 4× · PMID 36315906 · DOI 10.1080/21645515.2022.2133914
  8. Next-Generation Vaccines Against Neglected Diseases: New Promises from Genetically Modified Live-Attenuated Parasites and RNA Vaccines.
    Batista-Zauli MF, Brasil MECG, de Almeida-Júnior CR, de Abreu BGS, et al · · 2026 · PMID 42197496 · DOI 10.3390/microorganisms14051112

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