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MalariaPhase 1/2NCT05978037

A Study to Assess the Safety and Effectiveness of Two Experimental Malaria Vaccines

A Phase 1/2 study testing RH5.1 and/or RH5.2-VLP with Matrix-M in people with Malaria and Malaria,Falciparum, run by University of Oxford at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Malaria is a major public health problem. There were around 240 million cases of malaria and 627,000 deaths worldwide in 2020. There is a great need for a safe, effective malaria vaccine and the team at University of Oxford is trying to make vaccine(s) which can prevent serious illness and death. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Malaria, Malaria,Falciparum, Parasitic Disease
What is being tested?
RH5.1 and/or RH5.2-VLP with Matrix-M
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
1 siteUnited Kingdom
Study dates
18 Aug 2023to 30 Apr 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • • Healthy adult aged 18 to 45 years
  • 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 GP
  • Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study (see section 11.10)
  • Agreement to refrain from blood donation for the duration of the study
  • Able and willing to provide written informed consent to participate in the trial
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  • Additional inclusion criteria for groups 2 and 6:
  • Negative haemoglobinopathy screen (including sickle cell disease and alpha and beta thalassaemia) and normal G6PD levels
  • Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines (89)
  • Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment
  • Willingness to take a curative anti-malaria regimen following CHMI
  • Able to answer all questions on the informed consent questionnaire correctly at first or second attempt
  • Able to travel to CCVTM without using public transport

Who cannot join

  • • History of clinical malaria (any species) or previous participation in any malaria (vaccine) trial or CHMI
  • Travel to a clearly malaria endemic locality during the study period or within the preceding six months
  • Use of immunoglobulins or blood products (e.g. blood transfusion) in the last three months
  • Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination, with the exception of COVID-19 and flu vaccines, which should not be received between 14 days before to 7 days after any study vaccination
  • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
  • Concurrent involvement in another clinical trial involving an investigational product or planned involvement during the study period
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  • Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, 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
  • Any history of anaphylaxis in relation to vaccinations
  • Pregnancy, lactation or intention to become pregnant during the study
  • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
  • History of serious psychiatric condition that may affect participation in the study
  • Any other serious chronic illness requiring hospital specialist supervision
  • Suspected or known current alcohol misuse as defined by an alcohol intake of greater than 25 standard UK units every week
  • Suspected or known injecting drug use in the 5 years preceding enrolment
  • Hepatitis B surface antigen (HBsAg) detected in serum
  • Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless volunteer has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV ribonucleic acid (RNA) PCR at screening for this study)
  • Volunteers unable to be closely followed for social, geographic or psychological reasons.
  • Any clinically significant abnormal finding on biochemistry or haematology blood tests or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested.
  • Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
  • Inability of the study team to contact the volunteer's GP to confirm medical history and safety to participate
  • Additional exclusion criteria for Groups 2 and 6:
  • Body weight <50 kg or Body Mass Index (BMI) <18.0 at screening
  • 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
  • Receipt of a COVID-19 vaccine within 2 weeks before the day of CHMI or planned receipt of a COVID-19 vaccine or prior to expected completion of antimalarial treatment (around 2 to 3 weeks after day of challenge based on experience in previous P. falciparum CHMI studies to date)
  • An estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE).
  • Use of medications known to cause prolongation of the QT interval and existing contraindication to the use of Malarone
  • Use of medications known to have a potentially clinically significant interaction with Riamet and Malarone
  • Any other contraindications/known hypersensitivities to both Riamet and Malarone
  • Any clinical condition known to prolong the QT interval
  • History, or evidence at screening, of clinically significant arrhythmias, including clinically relevant bradycardia, prolonged QT interval or other clinically relevant ECG abnormalities
  • Disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia
  • Family history of congenital QT prolongation or sudden death
  • Positive family history in both 1st AND 2nd degree relatives < 50 years old for cardiac disease
  • History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait, G6PD deficiency or any haematological condition that could affect susceptibility to malaria infection
  • Additional exclusion criteria for optional FNA in Groups 1 and 3:
  • Regular use of anticoagulation or antiplatelet medication likely to induce bruising or bleeding on fine needle aspiration.
  • Any confirmed or suspected bleeding disorders.
  • History of lymphatic disorders (e.g. lymphoedema).
  • History of allergic disease or reactions to local anaesthetic such as lidocaine.
  • Any history of anaphylaxis in relation to local anaesthetic such as lidocaine.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Centre for Clinical Vaccinology & Tropical Medicine (CCVTM)

    Oxford, Oxfordshire, OX3 7LE

Other trials in United Kingdom

About this study

Official title: An Open Label Phase I/IIa Clinical Trial to Assess the Safety, Immunogenicity and Efficacy of the Malaria Vaccine Candidate RH5.2-virus-like Particle (VLP) in Matrix-MTM, and to Compare the Safety and Immunogenicity of the Malaria Vaccine Candidates RH5.2-VLP in Matrix-MTM and RH5.1 Soluble Protein in Matrix-MTM Used in Various Regimens

Malaria is a major public health problem. There were around 240 million cases of malaria and 627,000 deaths worldwide in 2020. There is a great need for a safe, effective malaria vaccine and the team at University of Oxford is trying to make vaccine(s) which can prevent serious illness and death.

This study is being done to assess an experimental malaria vaccine for its ability to prevent malaria illness. This is done using a 'blood-stage challenge model'. This is when volunteers are infected with malaria parasites using malaria-infected red blood cells.

Read more

The vaccine we are testing in this part of the study is called "RH5.2-VLP". It is given with an adjuvant called "Matrix-M". This is a substance to improve the body's response to a vaccination. RH5.2-VLP is being tested for the first time in humans in this trial. The Matrix-M adjuvant has been given to tens of thousands of people, with no major concerns, such as illness.

The aim is to use this vaccine and adjuvant to help the body make an immune response against parts of the malaria parasite. This study will assess:

  1. The safety of the vaccine in healthy participants.
  2. The response of the human immune system to the vaccine.
  3. The ability of the vaccine to prevent malaria illness (Group 2 only). We will do this by giving healthy adult participants (aged 18-45) three of the vaccines and/or expose participants to malaria infection at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital in Oxford. We will then do blood tests and collect information about any symptoms that occur after vaccination. There will be 19 to 54 visits, lasting between 3 months to 2 years and 2 months.
Being tested
RH5.1 and/or RH5.2-VLP with Matrix-M
Medical subject headings
Malaria, Malaria, Falciparum, Parasitic Diseases, Vector Borne Diseases, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RH5.1 and/or RH5.2-VLP with Matrix-MBiological

    The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum.

    The RH5.2 protein consists of the "stabilised" core region of PfRH5 antigen with SpyTag fused at the C-terminus. The RH5.2-SpyTag protein is conjugated to hepatitis B surface antigen (HBsAg)-SpyCatcher to produce the final RH5.2-VLP vaccine.

    The Matrix-M has been developed and manufactured by Novavax AB and is presented as a liquid solution in a glass vial.

Study groups in NCT05978037
Study groupRoleWhat they receive
Group 1: 10 µg RH5.2-VLP with Months 0,1 and 2 regimen.Active comparatorThis arm will receive monthly regimen of 3 doses of 10 µg of RH5.2-VLP with 50 µg Matrix-M .
Receives: Biological: RH5.1 and/or RH5.2-VLP with Matrix-M
Group 2: 10 µg RH5.2-VLP with Months 0,1 and 6 regimen.Active comparatorThis arm will receive 3 doses of 10 µg of RH5.2-VLP with 50 µg Matrix-M at Months 0, 1 and 6 (delayed regimen) and after Growth Inhibition Activity (GIA) immunogenicity review, will proceed to receive Controlled Human Malaria Infection (CHMI) 4 weeks after the last vaccination.
Receives: Biological: RH5.1 and/or RH5.2-VLP with Matrix-M
Group 3: 10 µg or 2 µg RH5.2-VLP with Months 0,1 and 6 regimen.Active comparatorThis arm will receive 2 doses of 10 µg of RH5.2-VLP with 50 µg Matrix-M at Months 0, 1 and 1 doses of 2 µg of RH5.2-VLP with 50 µg Matrix-M at Month 6 (delayed-fractional regimen).
Receives: Biological: RH5.1 and/or RH5.2-VLP with Matrix-M
Group 4: 10 µg RH5.2-VLP or 2 µg RH5.1 with Months 0,1 and 6 regimen.Active comparatorThis arm will receive 2 doses of 10 µg of RH5.2-VLP with 50 µg Matrix-M at Months 0, 1 and 1 doses of 2 µg of RH5.1 with 50 µg Matrix-M at Month 6 (delayed-fractional regimen, Prime with RH5.2-VLP then Boost with soluble RH5.1).
Receives: Biological: RH5.1 and/or RH5.2-VLP with Matrix-M
Group 5: 10 µg or 2 µg RH5.1 with Months 0,1 and 6 regimen.Active comparatorThis control arm will receive 2 doses of 10 µg of RH5.1 with 50 µg Matrix-M at Months 0, 1 and 1 doses of 2 µg of RH5.1 with 50 µg Matrix-M at Month 6 (delayed-fractional regimen with RH5.1).
Receives: Biological: RH5.1 and/or RH5.2-VLP with Matrix-M
Group 6: CHMI controlNo interventionThis control arm will be infectivity controls, so will not receive any vaccinations. Group 6 will only be recruited after observation of meeting positive GIA target.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To assess the safety of RH5.2-VLP and RH5.1 in Matrix-M in healthy volunteers at different doses and used in various regimens by assessing the occurrence of solicited local reactogenicity signs and symptoms

    Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination. These will be tabulated, detailing frequency, duration and severity of AEs. Haematological and biochemical laboratory values will be presented according to local grading scales.

    Measured: 7 days following each vaccination

  2. To assess efficacy of RH5.2-VLP in Matrix-M by assessing its impact on parasite multiplication rate (PMR) in vaccinated volunteers compared to infectivity controls, against P. falciparum in a blood-stage controlled human malaria infection (CHMI) model.

    Comparison of the PMR of the volunteers in Group 2 to the PMR of the malaria naive controls (Group 6) over 21 days of follow up period post-CHMI. PMR values will be collected initially as quantitative PCR data and calculated using a mathematical modelling.

    Measured: Maximum 21 days following CHMI

Secondary outcomes (4)

  1. To assess the humoral immunogenicity of RH5.2-VLP with Matrix-MTM and RH5.1 soluble protein with Matrix-M when administered to healthy volunteers at different doses and used in various regimens, with comparison before and after vaccination

    Serum ELISA response, antigen-specific antibody avidity measurement, antigen-specific antibody subclass/isotype measurement, quantitative antigen-specific IgG antibody levels (µg/mL readout) over time - analysis of peak responses and longevity, with comparison before and after vaccination

    Measured: From a number of key timepoints (Baseline up to day 790 (dependant on group))

  2. To compare the anti-RH5 serum IgG functional immunogenicity between the RH5.2-VLP and soluble RH5.1 protein when used at different doses and in various regimens

    In vitro GIA against 3D7 clone P. falciparum parasites using purified total IgG and a single-cycle pLDH readout assay, with comparison before and after vaccination.

    Measured: From a number of key timepoints (Baseline up to day 790 (dependant on group))

  3. To determine the phenotype of vaccine specific immune cells in axillary lymph nodes

    BCR sequencing with vaccine-specific B cells obtained from axillary lymph nodes to characterise the B cell repertoire (Group 1 \& 3 only)

    Measured: Day 140 (group 1) and Day 266 (group 3)

  4. To determine the frequency of vaccine specific immune cells in axillary lymph nodes

    BCR sequencing with vaccine-specific B cells obtained from axillary lymph nodes to characterise the B cell repertoire (Group 1 \& 3 only)

    Measured: Day 140 (group 1) and Day 266 (group 3)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2023
  2. Study start18 Aug 2023
  3. Primary completion30 Apr 2026
  4. Study completion30 Apr 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05978037
Sponsor's protocol ID
BIO-001
Status last verified
Jul 2026
First submitted
14 Jul 2023
Last updated
20 Jul 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RH5.1 and/or RH5.2-VLP with Matrix-M in people with Malaria and Malaria,Falciparum, run by University of Oxford at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To assess the safety of RH5.2-VLP and RH5.1 in Matrix-M in healthy volunteers at different doses and used in various regimens by assessing the occurrence of solicited local reactogenicity signs and symptoms (time frame: 7 days following each vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05978037.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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