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NCT02927145

A Challenge Study to Assess the Safety, Immunogenicity and Efficacy of a Malaria Vaccine Candidate

Completed Phase 1, PHASE2 Results posted Last updated 18 February 2022
What this trial tests

Phase 1, PHASE2 trial testing RH5.1/ ASO1 in Malaria in 88 participants. Completed in 27 June 2019.

Timeline
17 October 2016
Primary endpoint
27 June 2019
27 June 2019

Quick facts

Lead sponsorUniversity of Oxford
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposeprevention
Enrollment88
Start date17 October 2016
Primary completion27 June 2019
Estimated completion27 June 2019
Sites2 locations across United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

University of Oxford

Who can join

Adults 18 to 45, any sex, with Malaria. 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 RH5.1/AS01 Vaccine by Demonstrating a Reduced PMR in Vaccinated Subjects Compared to Infectivity Controls Against 3D7 Clone Parasites in a CHMI Model. Primary · Measured during CHMI

PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint for the Phase IIa stage of the trial, and comparison of the endpoint between the Groups 5 and 6 will constitute the primary analysis for efficacy.

GroupValue95% CI
Group 5-Phase IIa8.12± 1.13
Group 6-Phase IIa9.75± 2.46
Group 7-Phase IIa7.62± 1.44
Group 9 -Phase IIa11.22± 1.92
Safety of RH5.1/AS01 in Healthy Malaria-naïve Adults in the UK. Primary · 8 months

Solicited and unsolicited adverse events collected passively and actively for 28 days post each vaccination. Number of volunteers reporting any unsolicited AEs post-any vaccination, as reported to investigators or in electronic diaries.

GroupValue95% CI
Group 1-Phase Ia9
Group 2- Phase Ia11
Group 3-Phase Ia9
Group 4-Phase Ia10
Group 5-Phase IIa14
Group 7-Phase IIa3
the in Vitro Growth Inhibition Activity (GIA) Against 3D7 Clone P. Falciparum Parasites of IgG Purified From the Serum of Vaccinees. Primary · 2 weeks post final vaccination

The specific endpoints for GIA in vitro will be assessed from a titration of the purified IgG in the assay.

GroupValue95% CI
Group 1-Phase Ia75.2± 20.25
Group 2- Phase Ia69.9± 11.65
Group 3-Phase Ia71.3± 13.76
Group 4-Phase Ia71.6± 13.18
the Humoral Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens. Secondary · 2 weeks post final vaccination

Antibody responses to the RH5.1 protein generated by vaccination

GroupValue95% CI
Group 1-Phase Ia86.9± 51.75
Group 2- Phase Ia88.1± 40.11
Group 3-Phase Ia124.4± 81.62
Group 4-Phase Ia95.6± 56.07
the Cellular Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens. Secondary · 2 weeks post final vaccination

T cell responses to the RH5.1 protein generated by vaccination

GroupValue95% CI
Group 1-Phase Ia570± 439.4
Group 2- Phase Ia140.7± 343.9
Group 3-Phase Ia277.3± 328.4
Group 4-Phase Ia713.3± 396.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group 1
Serious: 0/12 (0%)
Deaths: 0/12
Group 2
Serious: 0/12 (0%)
Deaths: 0/12
Group 3
Serious: 1/12 (8%)
Deaths: 0/12
Group 4
Serious: 0/14 (0%)
Deaths: 0/14
Group 5
Serious: 1/17 (6%)
Deaths: 0/17
Group 6
Serious: 0/15 (0%)
Deaths: 0/15
Group 7
Serious: 1/9 (11%)
Deaths: 0/9
Group 8
Serious: 0/8 (0%)
Deaths: 0/8
Group 9
Serious: 0/6 (0%)
Deaths: 0/6

Serious adverse events (3 terms)

ReactionSystemGroup 1Group 2Group 3Group 4Group 5Group 6Group 7Group 8Group 9
PsoriasisSkin and subcutaneous tissue disorders
TonsilectomySurgical and medical procedures
PregnancyPregnancy, puerperium and perinatal conditions
Other adverse events (10 terms — click to expand)

ReactionSystemGroup 1Group 2Group 3Group 4Group 5Group 6Group 7Group 8Group 9
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painGeneral disorders
RhinitisGeneral disorders
Back PainMusculoskeletal and connective tissue disorders
HeadacheGeneral disorders
RhinorrhoeaGeneral disorders
Local ReactionGeneral disorders
NauseaGastrointestinal disorders
InsomniaGeneral disorders
AthralgiaMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Psoriasis, Tonsilectomy, Pregnancy.

Data from ClinicalTrials.gov NCT02927145 adverse events section.

Sponsor's own description

This is an open-label, multi-centre Phase I/IIa dose escalation blood-stage malaria CHMI trial to assess the safety, immunogenicity and efficacy of the candidate malaria vaccine RH5.1/AS01. All volunteers recruited will be healthy, malaria naïve adults aged between 18 and 45 years. Volunteers will be recruited and vaccinated at the CCVTM, Oxford; Guys and St Thomas' NIHR CRF, London; and the NIHR WTCRF, Southampton for the Phase Ia part of the trial, and at the CCVTM, Oxford and Guys and St Thomas' NIHR CRF, London for the Phase IIa stage.

Publications & conference data

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

  1. The Multirole of Liposomes in Therapy and Prevention of Infectious Diseases.
    Nisini R, Poerio N, Mariotti S, De Santis F, et al · · 2018 · cited 175× · PMID 29459867 · DOI 10.3389/fimmu.2018.00155
  2. Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination.
    Minassian AM, Silk SE, Barrett JR, Nielsen CM, et al · · 2021 · cited 117× · PMID 34223402 · DOI 10.1016/j.medj.2021.03.014
  3. The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target.
    Ragotte RJ, Higgins MK, Draper SJ. · · 2020 · cited 58× · PMID 32359873 · DOI 10.1016/j.pt.2020.04.003
  4. Liposomes as Adjuvants and Vaccine Delivery Systems.
    Tretiakova DS, Vodovozova EL. · · 2022 · cited 56× · PMID 35194485 · DOI 10.1134/s1990747822020076
  5. Production, quality control, stability, and potency of cGMP-produced <i>Plasmodium falciparum</i> RH5.1 protein vaccine expressed in <i>Drosophila</i> S2 cells.
    Jin J, Tarrant RD, Bolam EJ, Angell-Manning P, et al · · 2018 · cited 56× · PMID 30131879 · DOI 10.1038/s41541-018-0071-7
  6. Accelerating the clinical development of protein-based vaccines for malaria by efficient purification using a four amino acid C-terminal 'C-tag'.
    Jin J, Hjerrild KA, Silk SE, Brown RE, et al · · 2017 · cited 52× · PMID 28153778 · DOI 10.1016/j.ijpara.2016.12.001
  7. Protein/AS01<sub>B</sub> vaccination elicits stronger, more Th2-skewed antigen-specific human T follicular helper cell responses than heterologous viral vectors.
    Nielsen CM, Ogbe A, Pedroza-Pacheco I, Doeleman SE, et al · · 2021 · cited 48× · PMID 33763653 · DOI 10.1016/j.xcrm.2021.100207
  8. <i>Plasmodium falciparum</i> Malaria Vaccines and Vaccine Adjuvants.
    Bonam SR, Rénia L, Tadepalli G, Bayry J, et al · · 2021 · cited 29× · PMID 34696180 · DOI 10.3390/vaccines9101072

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