Plasmodium Falciparum MalariaPhase 1/2NCT01739036
A Phase I/IIa Sporozoite Challenge Study to Assess the Efficacy of Candidate Combination Malaria Vaccine Approaches Using the ChAd63 and MVA Vectors Encoding the Antigens ME-TRAP, CS and AMA1
A Phase 1/2 study testing ChAd63 CS/ME-TRAP, MVA CS/ME-TRAP and ChAd63 CS/ME-TRAP/AMA1 in people with Plasmodium Falciparum Malaria, run by University of Oxford at 3 sites in United Kingdom.
Trial summary
This is an open label, multi-centre phase I/IIa sporozoite-challenge trial to assess the safety, immunogenicity and efficacy of two combination ChAd63-MVA heterologous prime-boost vaccination regimens. All volunteers recruited will be healthy, malaria naïve adults aged between 18 and 45 years. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- ChAd63 CS/ME-TRAP, MVA CS/ME-TRAP and ChAd63 CS/ME-TRAP/AMA1
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Jan 2013to Oct 2013
- 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 adults 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 General Practitioner.
- 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 participate in the trial.
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- Reachable (24/7) by mobile phone during the period between CHMI and completion of antimalarial treatment.
- Willingness to take a curative anti-malaria regimen following CHMI.
- For volunteers not living in Oxford: agreement to stay in a hotel room close to the trial centre during a part of the study (from at least day 6.5 post mosquito bite until anti-malarial treatment is completed).
- Answer all questions on the informed consent quiz correctly.
- Group 3 volunteers only: have been sterilely protected against malaria following CHMI after receiving ChAd63-MVA prime-boost vaccination in the VAC045 clinical trial
Who cannot join
- History of clinical malaria (any species).
- Travel to a malaria endemic region during the study period or within the preceding six months with significant risk of malaria exposure.
- Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
- Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. For Group 3 participants, and Group 1 and 2 participants undergoing rechallenge, this exclusion criterion does not extend to the vaccines previously received for the VAC045 and VAC052 trials.
- 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).
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- Use of immunoglobulins or blood products within 3 months prior to enrolment.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. egg products, Kathon) or malaria infection.
- Any history of anaphylaxis post vaccination.
- History of clinically significant contact dermatitis.
- History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
- Pregnancy, lactation or intention to become pregnant during the study.
- Use of medications known to cause prolongation of the QT interval or to otherwise have a potentially clinically significant interaction with Riamet
- Any clinical condition known to prolong the QT interval
- History of cardiac arrhythmia, including clinically relevant bradycardia
- Disturbances of electrolyte balance, eg, hypokalaemia or hypomagnesaemia
- Family history of congenital QT prolongation or sudden death
- Contraindications to the use of all three proposed anti-malarial medications; Riamet, Malarone 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 enrolment.
- Seropositive for hepatitis B surface antigen (HBsAg).
- Seropositive for hepatitis C virus (antibodies to HCV) with positive PCR for hepatitis C at screening.
- An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.76
- 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
3 sites in 1 country.
United Kingdom3 sites
Infection and Immunity Section, Imperial College of Science, Technology and Medicine
London, SW7 2AZ
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxfordshire, OX3 7LE
Wellcome Trust CRF, Southampton General Hospital
Southampton, Hampshire, SO16 6YD
About this study
This is an open label, multi-centre phase I/IIa sporozoite-challenge trial to assess the safety, immunogenicity and efficacy of two combination ChAd63-MVA heterologous prime-boost vaccination regimens. All volunteers recruited will be healthy, malaria naïve adults aged between 18 and 45 years.
To determine the efficacy of each of two combinations of heterologous prime-boost immunisation strategies:
Read more
- ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS
- ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1
The study will be conducted at the University of Oxford's Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK and the Wellcome Trust Clinical Research Facility in Southampton, UK. The malaria challenge will take place at the insectary at Imperial College (Infection and Immunity Section) in London, UK.
- Conditions
- Plasmodium Falciparum Malaria
- Being tested
- ChAd63 CS/ME-TRAP, MVA CS/ME-TRAP, ChAd63 CS/ME-TRAP/AMA1, MVA CS/ME-TRAP/AMA1, Controlled Human Malaria Infection Administered by Mosquito Bite
- Keywords
- Malaria, Vaccine, Plasmodium, Falciparum
- Medical subject headings
- Malaria, Falciparum, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChAd63 CS/ME-TRAPBiological
Mixture of ChAd63 CS 5 x 1010 vp and ChAd63 ME-TRAP 5 x 1010 vp. Intramuscular needle injection.
MVA CS/ME-TRAPBiological
Mixture of MVA CS 2 x 108 pfu and MVA ME-TRAP 2 x 108 pfu. Intramuscular needle injection.
ChAd63 CS/ME-TRAP/AMA1Biological
Mixture of ChAd63 CS 5 x 1010 vp, ChAd63 ME-TRAP 5 x 1010 vp, and ChAd63 AMA1 5 x 1010 vp. Intramuscular needle injection.
MVA CS/ME-TRAP/AMA1Biological
Mixture of MVA CS 1.33 x 108 pfu, MVA ME-TRAP 1.33 x 108 pfu, and MVA AMA1 1.33 x 108 pfu. Intramuscular needle injection.
Controlled Human Malaria Infection Administered by Mosquito BiteOther
Approximately three weeks post MVA dosing.
| Study group | Role | What they receive |
|---|---|---|
| Group 4 | Active comparator | Unvaccinated control volunteers who undergo controlled human malaria infection. Receives: Other: Controlled Human Malaria Infection Administered by Mosquito Bite |
| Group 3 | Active comparator | Controlled human malaria infection administered at an interval of approximately 8-12 months after the initial controlled human malaria infection that the volunteers received in the VAC045 clinical trial. Receives: Other: Controlled Human Malaria Infection Administered by Mosquito Bite |
| Group 2 | Active comparator | Intramuscular administration of a mixture of ChAd63 ME-TRAP 5 x 1010 vp and ChAd63 CS 5 x 1010 vp and ChAd63 AMA1 5 x 1010 vp followed by intramuscular administration of a mixture of MVA ME-TRAP 1.33 x 108 pfu and MVA CS 1.33 x 108 pfu and MVA AMA1 1.33 x 108 pfu eight weeks later, followed by controlled human malaria infection 17-24 days later. Receives: Biological: ChAd63 CS/ME-TRAP/AMA1; Biological: MVA CS/ME-TRAP/AMA1; Other: Controlled Human Malaria Infection Administered by Mosquito Bite |
| Group 1 | Active comparator | Intramuscular administration of a mixture of ChAd63 ME-TRAP 5 x 1010 vp and ChAd63 CS 5 x 1010 vp, followed by intramuscular administration of a mixture of MVA ME-TRAP 2 x 108 pfu and MVA CS 2 x 108 pfu eight weeks later, followed by controlled human malaria infection 17-24 days later. Receives: Biological: ChAd63 CS/ME-TRAP; Biological: MVA CS/ME-TRAP; Other: Controlled Human Malaria Infection Administered by Mosquito Bite |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effectiveness of ChAd63-MVA ME-TRAP combined with ChAd63-CS and ChAd63-MVA AMA1 at preventing malaria infection.
To assess the efficacy of each of two combinations of heterologous prime-boost immunisation strategies:
- ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS
- ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1 Kaplan-Meier analysis of time to blood stage infection in vaccinees compared to unvaccinated control volunteers.
Comparison of the number of individuals who develop malaria infection between vaccinees and unvaccinated control volunteers.
Measured: Up to 30 days post challenge
Secondary outcomes (1)
Safety and immunogenicity of ChAd63-MVA ME-TRAP, ChAd63-MVA CS, ChAd63-MVA AMA1.
To assess the safety and immunogenicity of heterologous prime-boost immunisation of malaria-naïve individuals with ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS or with ChAd63-MVA CS plus ChAd63-MVA AMA1.
The safety of the vaccine regimens will be assessed by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements. The ability of the vaccines to induce malaria-specific immune responses immunogenicity) will be assessed by the following laboratory tests; (A) Interferon gamma ELISPOT. (B) Flow cytometry to measure T cell responses. Other laboratory investigations including microarray analysis may be performed.
Measured: Up to 7 months post first vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2012 (estimated)
- Study startJan 2013
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plasmodium Falciparum 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Adrian V S Hill, MD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01739036
- Sponsor's protocol ID
- VAC052
- Status last verified
- Nov 2013
- First submitted
- 28 Nov 2012
- Last updated
- 11 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Sporozoite Challenge Study to Assess the Efficacy of Candidate Combination Malaria Vaccine Approaches Using the ChAd63 and MVA Vectors Encoding the Antigens ME-TRAP, CS and AMA1
- ClinicalTrials.gov ID
- NCT01739036
- Acronym / sponsor ID
- VAC052
- Conditions
- Plasmodium Falciparum Malaria
- Keywords
- Malaria, Vaccine, Plasmodium, Falciparum
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 30 Nov 2012 (estimated)
- 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 an open label, multi-centre phase I/IIa sporozoite-challenge trial to assess the safety, immunogenicity and efficacy of two combination ChAd63-MVA heterologous prime-boost vaccination regimens. All volunteers recruited will be healthy, malaria naïve adults aged between 18 and 45 years.
To determine the efficacy of each of two combinations of heterologous prime-boost immunisation strategies:
- ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS
- ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1
The study will be conducted at the University of Oxford's Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK and the Wellcome Trust Clinical Research Facility in Southampton, UK. The malaria challenge will take place at the insectary at Imperial College (Infection and Immunity Section) in London, UK.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 4 | Active comparator | Other: Controlled Human Malaria Infection Administered by Mosquito BiteUnvaccinated control volunteers who undergo controlled human malaria infection. |
| Group 3 | Active comparator | Other: Controlled Human Malaria Infection Administered by Mosquito BiteControlled human malaria infection administered at an interval of approximately 8-12 months after the initial controlled human malaria infection that the volunteers received in the VAC045 clinical trial. |
| Group 2 | Active comparator | Biological: ChAd63 CS/ME-TRAP/AMA1, Biological: MVA CS/ME-TRAP/AMA1, Other: Controlled Human Malaria Infection Administered by Mosquito BiteIntramuscular administration of a mixture of ChAd63 ME-TRAP 5 x 1010 vp and ChAd63 CS 5 x 1010 vp and ChAd63 AMA1 5 x 1010 vp followed by intramuscular administration of a mixture of MVA ME-TRAP 1.33 x 108 pfu and MVA CS 1.33 x 108 pfu and MVA AMA1 1.33 x 108 pfu eight weeks later, followed by controlled human malaria infection 17-24 days later. |
| Group 1 | Active comparator | Biological: ChAd63 CS/ME-TRAP, Biological: MVA CS/ME-TRAP, Other: Controlled Human Malaria Infection Administered by Mosquito BiteIntramuscular administration of a mixture of ChAd63 ME-TRAP 5 x 1010 vp and ChAd63 CS 5 x 1010 vp, followed by intramuscular administration of a mixture of MVA ME-TRAP 2 x 108 pfu and MVA CS 2 x 108 pfu eight weeks later, followed by controlled human malaria infection 17-24 days later. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy adults 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 General Practitioner.
- 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.
Key exclusion criteria (30 listed)
- History of clinical malaria (any species).
- Travel to a malaria endemic region during the study period or within the preceding six months with significant risk of malaria exposure.
- Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
- Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. For Group 3 participants, and Group 1 and 2 participants undergoing rechallenge, this exclusion criterion does not extend to the vaccines previously received for the VAC045 and VAC052 trials.
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 |
|---|---|---|
| ChAd63 CS/ME-TRAPMixture of ChAd63 CS 5 x 1010 vp and ChAd63 ME-TRAP 5 x 1010 vp. Intramuscular needle injection. | Biological | Group 1 |
| MVA CS/ME-TRAPMixture of MVA CS 2 x 108 pfu and MVA ME-TRAP 2 x 108 pfu. Intramuscular needle injection. | Biological | Group 1 |
| ChAd63 CS/ME-TRAP/AMA1Mixture of ChAd63 CS 5 x 1010 vp, ChAd63 ME-TRAP 5 x 1010 vp, and ChAd63 AMA1 5 x 1010 vp. Intramuscular needle injection. | Biological | Group 2 |
| MVA CS/ME-TRAP/AMA1Mixture of MVA CS 1.33 x 108 pfu, MVA ME-TRAP 1.33 x 108 pfu, and MVA AMA1 1.33 x 108 pfu. Intramuscular needle injection. | Biological | Group 2 |
| Controlled Human Malaria Infection Administered by Mosquito BiteApproximately three weeks post MVA dosing. | Other | Group 1, Group 2, Group 3, Group 4 |
Primary outcome
The effectiveness of ChAd63-MVA ME-TRAP combined with ChAd63-CS and ChAd63-MVA AMA1 at preventing malaria infection.
Time frame: Up to 30 days post challenge
To assess the efficacy of each of two combinations of heterologous prime-boost immunisation strategies: 1. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS 2. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1 Kaplan-Meier analysis of time to blood stage infection in vaccinees compared to unvaccinated control volunteers. Comparison of the number of individuals who develop malaria infection between vaccinees and unvaccinated control volunteers.
1 secondary outcome
Safety and immunogenicity of ChAd63-MVA ME-TRAP, ChAd63-MVA CS, ChAd63-MVA AMA1.
Time frame: Up to 7 months post first vaccination
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 11 Nov 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 V S Hill, MD principal investigator
University of Oxford
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ChAd63 CS/ME-TRAP, MVA CS/ME-TRAP and ChAd63 CS/ME-TRAP/AMA1 in people with Plasmodium Falciparum Malaria, run by University of Oxford at 3 sites 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 11 inclusion and 30 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 11 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
The effectiveness of ChAd63-MVA ME-TRAP combined with ChAd63-CS and ChAd63-MVA AMA1 at preventing malaria infection. (time frame: Up to 30 days post challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Nov 2013.