AzTrials
AzTrials

Malaria,FalciparumPhase 2NCT03947190

A Study to Determine if New Types of Malaria Vaccines Are Safe, Effective and Lead to Immunity in Kenyan Adults

A Phase 2 study testing R21/Matrix-M, ChAd63/MVA ME-TRAP and intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge in people with Malaria,Falciparum, run by University of Oxford at 1 site in Kenya.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a phase IIb clinical trial in malaria-exposed individuals to assess the immunogenicity, safety and efficacy of the two vaccines in the context of controlled human malaria infection, P. falciparum sporozoite challenge (PfSPZ Challenge). Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Malaria,Falciparum
What is being tested?
R21/Matrix-M, ChAd63/MVA ME-TRAP and intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteKenya
Study dates
31 Aug 2022to 26 Feb 2023
Phase
Phase 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 adults aged 18 to 45 years
  • Able and willing (in the Investigator's opinion) to comply with all study requirements
  • Non-pregnant, non-lactating adult female or adult male
  • Agreement to refrain from blood donation during the study
  • Use of effective method of contraception for the duration of study for female participants. For those with no contraception, they will be referred for contraception at the relevant health facility. For female participants, we will ask them to attend with their family planning records for verification. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository)
  • Provide written informed consent
  • Plan to remain resident in the study area for 1 year following first dose of vaccination

Who cannot join

  • Clinically significant congenital abnormalities as judged by the study clinicians
  • 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).
  • Sickle cell disease
  • Any history of anaphylaxis in relation to vaccination
  • Clinically significant laboratory abnormality as judged by the study clinician
  • Blood transfusion within one month of enrolment
Show all 14Show fewer
  • Haemoglobin less than 11.3 g/dl for men and less than 10g/dl for in women, where judged to be clinically significant in the opinion of the investigator.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
  • Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
  • Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG)
  • Use of systemic antibiotics with known antimalarial activity within 30 days of administration of PfSPZ Challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
  • Women only; pregnancy, or an intention to become pregnant a day before challenge i.e. at C-1
  • Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
  • Confirmed parasite positive by PCR a day before challenge i.e. at C-1.

Trial locations and contacts

1 site in 1 country.

Kenya1 site

  • KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research - Coast

    Kilifi, PO Box 230, 80108

Other trials in Kenya

About this study

Official title: Safety, Immunogenicity, and Efficacy of R21/Matrix-M and ChAd63/MVA-ME-TRAP in the Context of Controlled Human Malaria Infection: A Phase IIb Trial in Kenyan Adults

This is a phase IIb clinical trial in malaria-exposed individuals to assess the immunogenicity, safety and efficacy of the two vaccines in the context of controlled human malaria infection, P. falciparum sporozoite challenge (PfSPZ Challenge).

Read the detailed description

A total of 64 participants will be enrolled for challenge and divided into four groups as follows:

  • 20 participants to receive R21/Matrix M (R21/MM) with intradermal PfSPZ Challenge;
  • 20 participants to receive viral-vectored ME-TRAP with intradermal PfSPZ Challenge;
  • 10 participants to receive R21/MM with direct venous inoculation PfSPZ Challenge; and
  • 14 participants comprising of the control group with intradermal PfSPZ Challenge.

Blood tests and clinical assessments will be conducted to screen out participants with health conditions that may impact participation in the study.

Being tested
R21/Matrix-M, ChAd63/MVA ME-TRAP, intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
Medical subject headings
Malaria, Falciparum

What participants receive

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

  • R21/Matrix-MBiological

    R21: Protein particle malaria vaccine candidate in Matrix-M: Saponin based vaccine adjuvant.

  • ChAd63/MVA ME-TRAPBiological

    ChAd63, chimpanzee adenovirus serotype 63; ME-TRAP, multiple epitope string fused to the thrombospondin-related adhesion protein; MVA, modified vaccinia Ankara.

  • intradermal injection (ID) or direct venous injection (DVI) of PfSPZ ChallengeBiological

    PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites.

Study groups in NCT03947190
Study groupRoleWhat they receive
Group 1ExperimentalGroup 1 adults (n=24) will be receiving, 4 weeks apart, three doses of 10µg R21 /50µg Matrix M vaccine, and a CHMI intradermally (ID) by inoculation of 22,500 PfSPZ Challenge.
Receives: Biological: R21/Matrix-M; Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
Group 2ExperimentalGroup 2 adults (n=24) will be receiving 5x10^10 vp ChAd63 ME-TRAP and 2x10^8 pfu MVA ME-TRAP vaccines, 8 weeks apart, and then a CHMI intradermally (ID) by inoculation of 22,500 PfSPZ Challenge, 4 weeks later.
Receives: Biological: ChAd63/MVA ME-TRAP; Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
Group 3ExperimentalGroup 3 adults (n=14) will be receiving, 4 weeks apart, three doses of 10µg R21 /50µg Matrix M vaccine, and a CHMI intravenously (DVI) by inoculation of 3,200 PfSPZ Challenge.
Receives: Biological: R21/Matrix-M; Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
Group 4ExperimentalGroup 4 adults (n=18) will be the control group receiving no vaccine, only a CHMI intradermally (ID) by inoculation of 22,500 PfSPZ Challenge.
Receives: Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge

What is being measured

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

  1. Occurrence of solicited local and systemic reactogenicity signs and symptoms, and unsolicited adverse events

    Assessing the safety and reactogenicity of adjuvanted R21/MM and heterologous prime- boost regime of ChAd63-MVA ME-TRAP in healthy adult volunteers

    Measured: Solicited AEs are collected for 7 days post vaccination and unsolicited AEs for 28 days post vaccination

  2. Occurrence of P. falciparum parasitemia assessed by PCR, and parasite density dynamics assessed by PCR, against malaria sporozoite challenge

    To assess the safety of intradermal sporozoite infection dose in semi-immune healthy adult volunteers

    Measured: up to 3 months after malaria sporozoite challenge

  3. Occurrence of P. falciparum parasitemia, assessed by qPCR

    To assess the efficacy of adjuvanted R21 and heterologous prime- boost regime of ChAd63-MVA ME-TRAP against malaria sporozoite challenge, in healthy adult volunteers

    Measured: from vaccination day up to 90 days after malaria sporozoite challenge

Secondary outcomes (3)

  1. To measure cellular immunogenicity assessed by ELISPOT

    Assessing cellular immunogenicity by ELISPOT to enumerate IFN-ƴ producing T cells

    Measured: from vaccination day up to 90 days after malaria sporozoite challenge

  2. To measure humoral immunogenicity assessed by ELISA

    Assessing humoral immunogenicity by ELISA to quantify antibodies to the vaccine components CS, NANP, TRAP and HBsAb.

    Measured: from vaccination day up to 90 days after malaria sporozoite challenge

  3. Parasite density dynamics assessed by qPCR

    To assess any differences in efficacy estimates with ID versus DVI challenge in individuals receiving R21/MM

    Measured: up to 3 months after malaria sporozoite challenge

Timeline

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

  1. First posted13 May 2019
  2. Study start31 Aug 2022
  3. Primary completion26 Feb 2023
  4. Study completion26 Feb 2023

Why it stopped: Due to US FDA hold on the challenge agent and funding concerns

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03947190
Sponsor's protocol ID
VAC074
Status last verified
Sep 2022
First submitted
7 May 2019
Last updated
20 Feb 2025
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kapulu MC, Orenge F, Kimani D, Kibwana E, Kibet H, Mutahi M, Datoo MS, Bellamy D, Musembi J, Ngoto O, Rashid H, Akinyi S, Mwatasa MH, Nyamako L, Keter K, Gatheru R, Mutiso A, Musyoki J, Mwacharo J, Abebe Y, James ER, Billingsley PF, Ngetsa C, Mosobo M, Makale J, Tawa B, Wamae K, Ochola-Oyier LI, Lawrie A, Ramos-Lopez F, Roberts R, Richie TL, Sim BKL, Hoffman SL, Ewer KJ, Hill AVS, Hamaluba M, Bejon P. Malaria vaccine protection against intradermal or venous parasites: a randomized phase 2b human challenge trial. Nat Med. 2026 Jan;32(1):178-185. doi: 10.1038/s41591-025-04107-6. Epub 2026 Jan 6.

    PubMed 41495411

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing R21/Matrix-M, ChAd63/MVA ME-TRAP and intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge in people with Malaria,Falciparum, run by University of Oxford at 1 site in Kenya.

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 7 inclusion and 14 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: stopped early, as of the sponsor's last update on 20 Feb 2025. 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 Kenya. 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 phase mean?

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 was stopped early (reason given: Due to US FDA hold on the challenge agent and funding concerns). Results are not available in the source record.

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?

Occurrence of solicited local and systemic reactogenicity signs and symptoms, and unsolicited adverse events (time frame: Solicited AEs are collected for 7 days post vaccination and unsolicited AEs for 28 days post vaccination). The study lists 3 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 NCT03947190, which also lists 1 linked publication.

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 Feb 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in