MalariaNCT01465048
Optimisation of Controlled Human Malaria Infection Using Sporozoites Administered by Needle and Syringe
A study testing Plasmodium falciparum sporozoites 2sites, Plasmodium falciparum sporozoites 1 site and Plasmodium falciparum sporozoites 1site in people with Malaria and Plasmodium Falciparum, run by University of Oxford at 1 site in United Kingdom.
Trial summary
This is an open label, human pilot study to optimise controlled human malaria infection (CHMI) administered by Plasmodium falciparum sporozoites (PfSPZ. Volunteers will be inoculated with 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, Plasmodium Falciparum
- What is being tested?
- Plasmodium falciparum sporozoites 2sites, Plasmodium falciparum sporozoites 1 site and Plasmodium falciparum sporozoites 1site
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2011to Feb 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only: Must practice continuous effective contraception for the duration of the study.
- Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study.
- Written informed consent to undergo CHMI.
- Reachable (24/7) by mobile phone during the whole study period.
- Willingness to take a curative anti-malaria regimen.
- For volunteers not living in Oxford: agreement to stay in a hotel room close to the trial centre during a part of the study (At least Day 6.5 post inoculation until 2 days after treatment commenced).
- Answer all questions on the informed consent quiz correctly.
Who cannot join
- History of clinical P. falciparum malaria.
- Travel to a malaria endemic region during the study period or within the preceding six months with positive P. falciparum serology at screening.
- Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
- Receipt of an investigational product in the 30 days preceding enrollment, or planned receipt during the study period.
- Prior receipt of an investigational malaria vaccine.
- 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).
Show all 23Show fewer
- Use of immunoglobulins or blood products within 3 months prior to enrollment.
- History of sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait.
- Pregnancy, lactation or intention to become pregnant during the study
- A history of allergic disease or reactions likely to be exacerbated by malaria infection.
- Contraindications to the use of all three proposed anti-malarial medications; Malarone, Riamet and Chloroquine.
- 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 abuse as defined by an alcohol intake of greater than 42 units every week.
- Suspected or known injecting drug abuse in the 5 years preceding enrollment.
- Seropositive for hepatitis B surface antigen (HBsAg).
- Seropositive for hepatitis C virus (antibodies to HCV).
- An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.39
- Positive family history in 1st and 2nd degree relatives < 50 years old for cardiac disease.
- Volunteers unable to be closely followed for social, geographic or psychological reasons.
- Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Oxford, OX3 7LJ
About this study
Official title: A Pilot Study to Optimise Controlled Human Malaria Infections Using Plasmodium Falciparum Sporozoites Administered by Needle and Syringe
This is an open label, human pilot study to optimise controlled human malaria infection (CHMI) administered by Plasmodium falciparum sporozoites (PfSPZ. Volunteers will be inoculated with PfSPZ Challenge. The route of administration and dose will vary in order to identify the optimal regimen that achieves the greatest infection rate in volunteers with Plasmodium falciparum. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected for each of the regimens.
Read the detailed description
Studies involving CHMI are a powerful tool for investigating malaria vaccine and prophylactic drug efficacy.CHMI has now become established as a key tool to assess the efficacy of novel malaria vaccines and drugs. As CHMI trials are carried out in a controlled environment, they allow unprecedented detailed evaluation of parasite growth and immunological responses, providing essential information for vaccine and drug development.
Out of three currently available methods of performing experimental human malaria infections (blood stage infection, mosquito bites and sporozoite infection), experimental injection directly by needle and syringe using aseptic, purified, cryopreserved sporozoites is, in principle, the most accurate and practical way of dosing sporozoites for challenge studies. Recently, Sanaria Inc have been able to overcome the technical issues associated with the production of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. As a result, an Investigational New Drug application (IND) was submitted to the U.S. Food and Drug Administration in February 2009, and a Phase 1 clinical trial with experimental challenge of volunteers was initiated in April 2009. Another trial sponsored by Sanaria to find the dose of aseptic, purified, cryopreserved sporozoites that should be used for experimental human malaria infections is currently ongoing with collaboration with the Radboud University Nijmegen Medical Center, The Netherlands.
This trial will be the first time aseptic, purified, cryopreserved P. falciparum sporozoites have been administered intramuscularly to humans.
- Conditions
- Malaria, Plasmodium Falciparum
- Being tested
- Plasmodium falciparum sporozoites 2sites, Plasmodium falciparum sporozoites 1 site, Plasmodium falciparum sporozoites 1site
- Keywords
- Malaria, Protozoan Infections, Parasitic Diseases, Malaria Challenge
- Medical subject headings
- Malaria, Malaria, Falciparum, Protozoan Infections, Parasitic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasmodium falciparum sporozoites 2sitesBiological
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intradermal injection sites
Plasmodium falciparum sporozoites 1 siteBiological
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intramuscular injection sites
Plasmodium falciparum sporozoites 1siteBiological
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 25,000 sporozoites, 50ulx2, 2 intramuscular injection sites
| Study group | Role | What they receive |
|---|---|---|
| Plasmodium falciparum sporozoites 2sites | Experimental | 2,500 sporozoites intradermally Receives: Biological: Plasmodium falciparum sporozoites 2sites |
| Plasmodium falciparum sporozoites 1 site | Experimental | 2,500 sporozoites intramuscularly Receives: Biological: Plasmodium falciparum sporozoites 1 site |
| Plasmodium falciparum sporozoites 1site | Experimental | 25,000 sporozoites intramuscularly Receives: Biological: Plasmodium falciparum sporozoites 1site |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Infected
To determine the infectivity rates of PfSPZ Challenge administered in various regimens by thick film microscopy and highly sensitive PCR for Plasmodium falciparum DNA.
Measured: 21 days post administration of PfSPZ Challenge
Secondary outcomes (2)
Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising.
To assess the safety of PfSPZ Challenge administered in various regimens by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements, including lab reports and adverse events.
Measured: Participants will be followed for the duration of the study, an expected average of 3 months
Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens
To determine the parasite growth dynamics of PfSPZ Challenge administered in various regimens using highly sensitive PCR for Plasmodium falciparum DNA.
Measured: 21 days post administration of PfSPZ Challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2011 (estimated)
- Study startOct 2011
- Primary completionFeb 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Sanaria Inc.
- Responsible party
- Sponsor
- Investigators
- Adrian VS Hill, DPhil FRCP, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01465048
- Sponsor's protocol ID
- VAC049
- Status last verified
- Jun 2013
- First submitted
- 27 Oct 2011
- Last updated
- 24 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Mukhopadhyay ES, Bellamy DG, Tinto H, Hamaluba M, Truby A, Salman AM, Hill AVS. Naturally acquired immune responses to alpha-gal in malaria endemic settings and pre-clinical efficacy testing with R21/MM. Vaccine. 2025 Dec 5;68:127897. doi: 10.1016/j.vaccine.2025.127897. Epub 2025 Nov 1.
PubMed 41176969Longley RJ, Halbroth BR, Salman AM, Ewer KJ, Hodgson SH, Janse CJ, Khan SM, Hill AVS, Spencer AJ. Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine. Infect Immun. 2017 Feb 23;85(3):e00641-16. doi: 10.1128/IAI.00641-16. Print 2017 Mar.
PubMed 28031267Hodgson SH, Llewellyn D, Silk SE, Milne KH, Elias SC, Miura K, Kamuyu G, Juma EA, Magiri C, Muia A, Jin J, Spencer AJ, Longley RJ, Mercier T, Decosterd L, Long CA, Osier FH, Hoffman SL, Ogutu B, Hill AV, Marsh K, Draper SJ. Changes in Serological Immunology Measures in UK and Kenyan Adults Post-controlled Human Malaria Infection. Front Microbiol. 2016 Oct 13;7:1604. doi: 10.3389/fmicb.2016.01604. eCollection 2016.
PubMed 27790201Sheehy SH, Spencer AJ, Douglas AD, Sim BK, Longley RJ, Edwards NJ, Poulton ID, Kimani D, Williams AR, Anagnostou NA, Roberts R, Kerridge S, Voysey M, James ER, Billingsley PF, Gunasekera A, Lawrie AM, Hoffman SL, Hill AV. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe. PLoS One. 2013 Jun 18;8(6):e65960. doi: 10.1371/journal.pone.0065960. Print 2013.
PubMed 23823332
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Optimise Controlled Human Malaria Infections Using Plasmodium Falciparum Sporozoites Administered by Needle and Syringe
- ClinicalTrials.gov ID
- NCT01465048
- Acronym / sponsor ID
- VAC049
- Conditions
- Malaria, Plasmodium Falciparum
- Keywords
- Malaria, Protozoan Infections, Parasitic Diseases, Malaria Challenge
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Sanaria Inc.
- Study start
- Oct 2011
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 4 Nov 2011 (estimated)
- Results
- Posted 28 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, human pilot study to optimise controlled human malaria infection (CHMI) administered by Plasmodium falciparum sporozoites (PfSPZ. Volunteers will be inoculated with PfSPZ Challenge. The route of administration and dose will vary in order to identify the optimal regimen that achieves the greatest infection rate in volunteers with Plasmodium falciparum. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected for each of the regimens.
Detailed description
Studies involving CHMI are a powerful tool for investigating malaria vaccine and prophylactic drug efficacy.CHMI has now become established as a key tool to assess the efficacy of novel malaria vaccines and drugs. As CHMI trials are carried out in a controlled environment, they allow unprecedented detailed evaluation of parasite growth and immunological responses, providing essential information for vaccine and drug development.
Out of three currently available methods of performing experimental human malaria infections (blood stage infection, mosquito bites and sporozoite infection), experimental injection directly by needle and syringe using aseptic, purified, cryopreserved sporozoites is, in principle, the most accurate and practical way of dosing sporozoites for challenge studies. Recently, Sanaria Inc have been able to overcome the technical issues associated with the production of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. As a result, an Investigational New Drug application (IND) was submitted to the U.S. Food and Drug Administration in February 2009, and a Phase 1 clinical trial with experimental challenge of volunteers was initiated in April 2009. Another trial sponsored by Sanaria to find the dose of aseptic, purified, cryopreserved sporozoites that should be used for experimental human malaria infections is currently ongoing with collaboration with the Radboud University Nijmegen Medical Center, The Netherlands.
This trial will be the first time aseptic, purified, cryopreserved P. falciparum sporozoites have been administered intramuscularly to humans.
Study design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Plasmodium falciparum sporozoites 2sites | Experimental | Biological: Plasmodium falciparum sporozoites 2sites2,500 sporozoites intradermally |
| Plasmodium falciparum sporozoites 1 site | Experimental | Biological: Plasmodium falciparum sporozoites 1 site2,500 sporozoites intramuscularly |
| Plasmodium falciparum sporozoites 1site | Experimental | Biological: Plasmodium falciparum sporozoites 1site25,000 sporozoites intramuscularly |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Women only: Must practice continuous effective contraception for the duration of the study.
- Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study.
- Written informed consent to undergo CHMI.
- Reachable (24/7) by mobile phone during the whole study period.
- Willingness to take a curative anti-malaria regimen.
Key exclusion criteria (23 listed)
- History of clinical P. falciparum malaria.
- Travel to a malaria endemic region during the study period or within the preceding six months with positive P. falciparum serology at screening.
- Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
- Receipt of an investigational product in the 30 days preceding enrollment, or planned receipt during the study period.
- Prior receipt of an investigational malaria vaccine.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasmodium falciparum sporozoites 2sitesAseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intradermal injection sites | Biological | Plasmodium falciparum sporozoites 2sites |
| Plasmodium falciparum sporozoites 1 siteAseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intramuscular injection sites | Biological | Plasmodium falciparum sporozoites 1 site |
| Plasmodium falciparum sporozoites 1siteAseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 25,000 sporozoites, 50ulx2, 2 intramuscular injection sites | Biological | Plasmodium falciparum sporozoites 1site |
Primary outcome
Number of Participants Infected
Time frame: 21 days post administration of PfSPZ Challenge
To determine the infectivity rates of PfSPZ Challenge administered in various regimens by thick film microscopy and highly sensitive PCR for Plasmodium falciparum DNA.
2 secondary outcomes
Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising.
Time frame: Participants will be followed for the duration of the study, an expected average of 3 months
Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens
Time frame: 21 days post administration of PfSPZ Challenge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41176969Mukhopadhyay ES, Bellamy DG, Tinto H, Hamaluba M, Truby A, Salman AM, Hill AVS. Naturally acquired immune responses to alpha-gal in malaria endemic settings and pre-clinical efficacy testing with R21/MM. Vaccine. 2025 Dec 5;68:127897. doi: 10.1016/j.vaccine.2025.127897. Epub 2025 Nov 1.
- Derived from this study: PubMed 28031267Longley RJ, Halbroth BR, Salman AM, Ewer KJ, Hodgson SH, Janse CJ, Khan SM, Hill AVS, Spencer AJ. Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine. Infect Immun. 2017 Feb 23;85(3):e00641-16. doi: 10.1128/IAI.00641-16. Print 2017 Mar.
- Derived from this study: PubMed 27790201Hodgson SH, Llewellyn D, Silk SE, Milne KH, Elias SC, Miura K, Kamuyu G, Juma EA, Magiri C, Muia A, Jin J, Spencer AJ, Longley RJ, Mercier T, Decosterd L, Long CA, Osier FH, Hoffman SL, Ogutu B, Hill AV, Marsh K, Draper SJ. Changes in Serological Immunology Measures in UK and Kenyan Adults Post-controlled Human Malaria Infection. Front Microbiol. 2016 Oct 13;7:1604. doi: 10.3389/fmicb.2016.01604. eCollection 2016.
- Derived from this study: PubMed 23823332Sheehy SH, Spencer AJ, Douglas AD, Sim BK, Longley RJ, Edwards NJ, Poulton ID, Kimani D, Williams AR, Anagnostou NA, Roberts R, Kerridge S, Voysey M, James ER, Billingsley PF, Gunasekera A, Lawrie AM, Hoffman SL, Hill AV. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe. PLoS One. 2013 Jun 18;8(6):e65960. doi: 10.1371/journal.pone.0065960. Print 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adrian VS Hill, DPhil FRCP principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Plasmodium falciparum sporozoites 2sites, Plasmodium falciparum sporozoites 1 site and Plasmodium falciparum sporozoites 1site in people with Malaria and Plasmodium 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 7 inclusion and 23 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 24 Jun 2013. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Infected (time frame: 21 days post administration of PfSPZ Challenge). 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 NCT01465048, which also lists 4 linked publications.
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 24 Jun 2013.