MalariaNCT03906474
VAC063C: A Study to Assess Repeat Blood-stage P. Falciparum Infection
A study of Malaria, run by University of Oxford at 1 site in United Kingdom.
Trial summary
This is a clinical study to assess the safety of primary, secondary and tertiary blood-stage controlled human Plasmodium falciparum malaria infection of healthy malaria-naïve UK adults, as well as to evaluate any effect of prior exposure to a blood-stage controlled human malaria infection (CHMI) on the parasite… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 6 Nov 2018to 14 Feb 2019
- Phase
- Interventional
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults aged 18 to 50 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 General Practitioner (GP).
- For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and on the day prior to blood-stage CHMI, and prior to the start of antimalarial treatment.
- Provide written informed consent.
- Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines.
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- Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment.
- Willingness to take a curative anti-malarial regimen following CHMI.
- Answer all questions on the informed consent questionnaire correctly.
- For Groups 1-2: completion of primary or secondary challenge in the VAC063 trial, curative anti-malarials and follow-up (up until at least the C+28 visit).
Who cannot join
- Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
- Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator.
- Administration of immunoglobulins and/or any blood products at any time in the past.
- 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).
- Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
- History of malaria chemoprophylaxis within 30 days prior to CHMI.
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- Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
- History of allergic disease or reactions likely to be exacerbated by malaria infection.
- Pregnancy, lactation or willingness/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 likely to 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 25 units every week.
- Suspected or known injecting drug abuse in the 5 years preceding enrolment.
- Seropositive for hepatitis B surface antigen (HBsAg) at screening.
- Seropositive for HIV virus (antibodies to HIV) at screening
- Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study).
- History of clinical malaria (any species - NOT applicable to prior challenge in VAC063 study for Groups 1 and 2).
- Travel to a malaria endemic region during the study period or within the previous six months.
- Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis.
- 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 to allow Investigator to assess safety to participate.
- History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
- Laboratory evidence of G6PD deficiency at screening.
- Laboratory evidence of haemoglobinopathy at screening.
- 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.
- Contraindications to the use of both Riamet and Malarone.
- Any clinical condition known to prolong the QT interval.
- 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 cardiac arrhythmia, including clinically relevant bradycardia.
- Volunteer unable to be closely followed for social, geographic or psychological reasons.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
CCVTM, University of Oxford, Churchill Hospital
Oxford, OX3 7LE
About this study
Official title: A Clinical Study to Assess the Safety of Primary, Secondary and Tertiary Blood-stage Controlled Human Plasmodium Falciparum Malaria Infection of Healthy Malaria-naïve UK Adults, and to Characterise Parasite Growth Dynamics
This is a clinical study to assess the safety of primary, secondary and tertiary blood-stage controlled human Plasmodium falciparum malaria infection of healthy malaria-naïve UK adults, as well as to evaluate any effect of prior exposure to a blood-stage controlled human malaria infection (CHMI) on the parasite multiplication rate.
As a secondary objective, the immune response to primary, secondary and tertiary P. falciparum blood-stage infection, as well as gametocytaemia, will also be assessed.
Read the detailed description
Nine to seventeen healthy adult volunteers, aged between 18 and 50 years, will be recruited and receive a blood-stage controlled human malaria infection (CHMI) at the CCVTM, Oxford. Of these volunteers, three will be newly recruited, malaria-naïve volunteers, who will receive a primary CHMI.
The remaining volunteers will be invited to be involved in this study, following previous participation in the VAC063 study (ClinicalTrials.gov Identifier: NCT02927145). VAC063 was a study to assess the safety, immune responses and efficacy of the new malaria vaccine RH5.1/AS01. As part of this study, control volunteers, who did not receive a vaccine, received a blood-stage CHMI, or "challenge", in order to compare to the vaccinated volunteers. Some control (unvaccinated) participants received two challenges and some received just one challenge, therefore, in this study, participants who previously took part in VAC063 will receive either a third or second malaria challenge.
Volunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously. Blood will then be taken at regular intervals to measure the parasite growth, quantify the sexual parasite forms and assess the immune response to primary, secondary or tertiary P. falciparum CHMI.
When volunteers are diagnosed with malaria, treatment with a standard antimalarial course of oral artemether-lumefantrine (Riamet) will be given over 3 days.
Volunteers who take part in this study will be involved in the trial for approximately 3 months.
- Conditions
- Malaria
- Being tested
- Blood-stage controlled human P. falciparum malaria infection
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood-stage controlled human P. falciparum malaria infectionBiological
Volunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | A third blood-stage controlled human P. falciparum malaria infection will be administered to individuals who have previously been exposed to two blood-stage challenges in the VAC063 trial. Group 1 will be challenged in parallel with Groups 2 (undergoing a second challenge) and 3 (malaria-naïve controls). Receives: Biological: Blood-stage controlled human P. falciparum malaria infection |
| Group 2 | Experimental | A second blood-stage controlled human P. falciparum malaria infection will be administered to individuals who have previously been exposed to one blood-stage challenge in the VAC063 trial. Group 2 will be challenged in parallel with Groups 1 (undergoing a third challenge) and 3 (malaria-naïve controls). Receives: Biological: Blood-stage controlled human P. falciparum malaria infection |
| Group 3 | Experimental | Malaria-naïve controls will receive a primary blood-stage controlled human P. falciparum malaria infection. Group 3 will be challenged in parallel with Groups 1 (undergoing a third challenge) and 2 (undergoing a second challenge). Receives: Biological: Blood-stage controlled human P. falciparum malaria infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of primary, secondary and tertiary blood-stage controlled human Plasmodium falciparum malaria infection of healthy malaria-naïve UK adults, as measured by (S)AE occurrences.
Measured: 3 months
The effect of prior blood-stage CHMI on parasite multiplication rate following tertiary (Group 1) and secondary (Group 2) homologous CHMI in unvaccinated volunteers, compared to primary challenge in new malaria naïve controls (Group 3).
The qPCR-derived parasite multiplication rate (PMR) will be the primary endpoint for the trial, and reporting of the endpoint for Groups 1-3 will constitute the primary analysis.
Measured: 3 months
Secondary outcomes (2)
P. falciparum specific immunogenicity following primary, secondary and tertiary P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses
Measured: 2 years
Gametocytaemia following primary, secondary and tertiary P. falciparum blood-stage infection.
Gametocytaemia will be measured by PCR.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2019
- Study start6 Nov 2018
- Primary completion14 Feb 2019
- Study completion14 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angela M Minassian, MBBS MA DPhil MRCP FRCPath, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03906474
- Sponsor's protocol ID
- VAC063C
- Status last verified
- Apr 2019
- First submitted
- 8 Oct 2018
- Last updated
- 8 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Salkeld J, Themistocleous Y, Barrett JR, Mitton CH, Rawlinson TA, Payne RO, Hou MM, Khozoee B, Edwards NJ, Nielsen CM, Sandoval DM, Bach FA, Nahrendorf W, Ramon RL, Baker M, Ramos-Lopez F, Folegatti PM, Quinkert D, Ellis KJ, Poulton ID, Lawrie AM, Cho JS, Nugent FL, Spence PJ, Silk SE, Draper SJ, Minassian AM. Repeat controlled human malaria infection of healthy UK adults with blood-stage Plasmodium falciparum: Safety and parasite growth dynamics. Front Immunol. 2022 Aug 22;13:984323. doi: 10.3389/fimmu.2022.984323. eCollection 2022.
PubMed 36072606
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study to Assess the Safety of Primary, Secondary and Tertiary Blood-stage Controlled Human Plasmodium Falciparum Malaria Infection of Healthy Malaria-naïve UK Adults, and to Characterise Parasite Growth Dynamics
- ClinicalTrials.gov ID
- NCT03906474
- Acronym / sponsor ID
- VAC063C
- Conditions
- Malaria
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 6 Nov 2018 (actual)
- Primary completion
- 14 Feb 2019 (actual)
- Study completion
- 14 Feb 2019 (actual)
- First posted
- 8 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a clinical study to assess the safety of primary, secondary and tertiary blood-stage controlled human Plasmodium falciparum malaria infection of healthy malaria-naïve UK adults, as well as to evaluate any effect of prior exposure to a blood-stage controlled human malaria infection (CHMI) on the parasite multiplication rate.
As a secondary objective, the immune response to primary, secondary and tertiary P. falciparum blood-stage infection, as well as gametocytaemia, will also be assessed.
Detailed description
Nine to seventeen healthy adult volunteers, aged between 18 and 50 years, will be recruited and receive a blood-stage controlled human malaria infection (CHMI) at the CCVTM, Oxford. Of these volunteers, three will be newly recruited, malaria-naïve volunteers, who will receive a primary CHMI.
The remaining volunteers will be invited to be involved in this study, following previous participation in the VAC063 study (ClinicalTrials.gov Identifier: NCT02927145). VAC063 was a study to assess the safety, immune responses and efficacy of the new malaria vaccine RH5.1/AS01. As part of this study, control volunteers, who did not receive a vaccine, received a blood-stage CHMI, or "challenge", in order to compare to the vaccinated volunteers. Some control (unvaccinated) participants received two challenges and some received just one challenge, therefore, in this study, participants who previously took part in VAC063 will receive either a third or second malaria challenge.
Volunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously. Blood will then be taken at regular intervals to measure the parasite growth, quantify the sexual parasite forms and assess the immune response to primary, secondary or tertiary P. falciparum CHMI.
When volunteers are diagnosed with malaria, treatment with a standard antimalarial course of oral artemether-lumefantrine (Riamet) will be given over 3 days.
Volunteers who take part in this study will be involved in the trial for approximately 3 months.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: Blood-stage controlled human P. falciparum malaria infectionA third blood-stage controlled human P. falciparum malaria infection will be administered to individuals who have previously been exposed to two blood-stage challenges in the VAC063 trial. Group 1 will be challenged in parallel with Groups 2 (undergoing a second challenge) and 3 (malaria-naïve controls). |
| Group 2 | Experimental | Biological: Blood-stage controlled human P. falciparum malaria infectionA second blood-stage controlled human P. falciparum malaria infection will be administered to individuals who have previously been exposed to one blood-stage challenge in the VAC063 trial. Group 2 will be challenged in parallel with Groups 1 (undergoing a third challenge) and 3 (malaria-naïve controls). |
| Group 3 | Experimental | Biological: Blood-stage controlled human P. falciparum malaria infectionMalaria-naïve controls will receive a primary blood-stage controlled human P. falciparum malaria infection. Group 3 will be challenged in parallel with Groups 1 (undergoing a third challenge) and 2 (undergoing a second challenge). |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Healthy adults aged 18 to 50 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 General Practitioner (GP).
- For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and on the day prior to blood-stage CHMI, and prior to the start of antimalarial treatment.
- Provide written informed consent.
Key exclusion criteria (33 listed)
- Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
- Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator.
- Administration of immunoglobulins and/or any blood products at any time in the past.
- 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).
- Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
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 |
|---|---|---|
| Blood-stage controlled human P. falciparum malaria infectionVolunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously. | Biological | Group 1, Group 2, Group 3 |
Primary outcome
The safety of primary, secondary and tertiary blood-stage controlled human Plasmodium falciparum malaria infection of healthy malaria-naïve UK adults, as measured by (S)AE occurrences.
Time frame: 3 months
The effect of prior blood-stage CHMI on parasite multiplication rate following tertiary (Group 1) and secondary (Group 2) homologous CHMI in unvaccinated volunteers, compared to primary challenge in new malaria naïve controls (Group 3).
Time frame: 3 months
The qPCR-derived parasite multiplication rate (PMR) will be the primary endpoint for the trial, and reporting of the endpoint for Groups 1-3 will constitute the primary analysis.
2 secondary outcomes
P. falciparum specific immunogenicity following primary, secondary and tertiary P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses
Time frame: 2 years
Gametocytaemia following primary, secondary and tertiary P. falciparum blood-stage infection.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2019.
- Derived from this study: PubMed 36072606Salkeld J, Themistocleous Y, Barrett JR, Mitton CH, Rawlinson TA, Payne RO, Hou MM, Khozoee B, Edwards NJ, Nielsen CM, Sandoval DM, Bach FA, Nahrendorf W, Ramon RL, Baker M, Ramos-Lopez F, Folegatti PM, Quinkert D, Ellis KJ, Poulton ID, Lawrie AM, Cho JS, Nugent FL, Spence PJ, Silk SE, Draper SJ, Minassian AM. Repeat controlled human malaria infection of healthy UK adults with blood-stage Plasmodium falciparum: Safety and parasite growth dynamics. Front Immunol. 2022 Aug 22;13:984323. doi: 10.3389/fimmu.2022.984323. eCollection 2022.
- Individual participant dataSharing planned: Undecided
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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.
Angela M Minassian, MBBS MA DPhil MRCP FRCPath 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 of Malaria, 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 10 inclusion and 33 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 8 Apr 2019. 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?
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?
The safety of primary, secondary and tertiary blood-stage controlled human Plasmodium falciparum malaria infection of healthy malaria-naïve UK adults, as measured by (S)AE occurrences. (time frame: 3 months). 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 NCT03906474, 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 8 Apr 2019.