MalariaPhase 1NCT03084289
A Study to Assess the Safety and Immunogenicity of a Candidate Malaria Vaccine Using Novel Routes of Administration
A Phase 1 study testing ChAd63-METRAP and MVA ME-TRAP in people with Malaria, run by University of Oxford at 1 site in United Kingdom.
Trial summary
The purpose of this study is to assess the safety and immunogenicity of novel routes of administration of the candidate malaria vaccines ChAd63 encoding ME-TRAP and MVA encoding ME-TRAP. 30-33 Healthy adult volunteers will be recruited in Oxford. All vaccinations will be administered intravenously or subcutaneously. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- ChAd63-METRAP and MVA ME-TRAP
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Mar 2017to 6 Jul 2020
- Phase
- Phase 1
- 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
- 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 vaccination
- Agreement to refrain from blood donation during the course of the study
- Provide written informed consent
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.
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
- 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 hereditary angioedema, acquired angioedema, or idiopathic angioedema.
Show all 21Show fewer
- Any history of anaphylaxis in relation to vaccination
- 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
- Bleeding disorder (e.g. Factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture
- 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)
- History of clinical malaria (any species)
- Travel to a malaria endemic region during the study period or within the previous six months
- Any clinically significant abnormal finding on screening biochemistry, coagulation, 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 and safety to participate
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital
Oxford, OX3 7LE
About this study
Official title: A Phase I Study to Assess the Safety and Immunogenicity of Novel Routes of Administration of Plasmodium Falciparum Malaria Vaccine Candidates ChAd63 and MVA Encoding ME-TRAP.
The purpose of this study is to assess the safety and immunogenicity of novel routes of administration of the candidate malaria vaccines ChAd63 encoding ME-TRAP and MVA encoding ME-TRAP.
30-33 Healthy adult volunteers will be recruited in Oxford.
All vaccinations will be administered intravenously or subcutaneously. Each volunteer will receive a single vaccination of ChAd63 ME-TRAP or MVA ME-TRAP at different doses depending on the group.
Read the detailed description
Group1 consists of 3 volunteers receiving i.v. ChAd63 ME-TRAP at the dose of 5x10^8 vp.
Group 2 consists of 3 volunteers receiving i.v. ChAd63 ME-TRAP at the dose of 5x10^9 vp.
Group 3 consists of 9 volunteers receiving i.v. ChAd63 ME-TRAP at the dose of 5x10^10vp.
Group 4 consists of 3 volunteers receiving s.c. ChAd63 ME-TRAP at the dose of 5x10^10 vp.
Group 5 consists of 3 volunteers receiving s.c. ChAd63 ME-TRAP at the dose of 2x10^11 vp.
Group 6 consists of 3 volunteers receiving i.v. MVA ME-TRAP at the dose of 2x10^6 pfu.
Group 7 consists of 3 volunteers receiving i.v. MVA ME-TRAP at the dose of 2x10^7 pfu.
Group 8 consists of 3-6 volunteers receiving i.v. MVA ME-TRAP at the dose of 2x10^8 pfu.
The first Group 1 volunteer to receive intravenous ChAd63 ME-TRAP will be vaccinated alone. Safety data for the first 72 hours following vaccination must be satisfactorily reviewed before the remaining group 1 volunteers are vaccinated. The safety data for the first 72 hours following vaccination for all the volunteers in the group will again be reviewed before the first volunteer in the higher dose group 2 is vaccinated. Safety data for the first 72 hours following vaccination of this volunteer must be satisfactorily reviewed before the remaining group 2 volunteers are vaccinated. Similarly the safety data for the first 72 hours following vaccination for all the volunteers in this group will again be reviewed before the first volunteer in the higher dose group 3 is vaccinated. Once there is satisfactory review of the safety data of the first 72 hours post vaccination for this volunteer, the remaining group 3 volunteers will be enrolled to receive IV vaccination.
An identical process will be followed for the enrolment of groups 6 - 8 receiving MVA ME-TRAP intravenously. Once three group 8 volunteers have received vaccination and there has been a satisfactory safety review at 72 hours, the chief investigator will make a decision as to whether or not to enrol the final three volunteers on the basis of the immunology data - and whether further determination of immunogenicity is needed.
In parallel with Group 1, the first Group 4 volunteer to receive subcutaneous Chad63 ME-TRAP will be vaccinated alone. Safety data for the first 72 hours following vaccination must be satisfactorily reviewed before the remaining group 4 volunteers are vaccinated. The safety data for the first 72 hours following vaccination for all the volunteers in the group will again be reviewed before the first volunteer in the higher dose group 5 is vaccinated. Once there is satisfactory review of the safety data of the first 72 hours post vaccination for this volunteer, the remaining group 5 volunteers will be enrolled to receive SC vaccination.
- Conditions
- Malaria
- Being tested
- ChAd63-METRAP, MVA ME-TRAP
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChAd63-METRAPBiological
The candidate vaccine applicable to the clinical trial is the Chimpanzee adenovirus 63 expressing Multiple epitopes and thrombospondin related adhesion protein.
MVA ME-TRAPBiological
The candidate vaccine applicable to the clinical trial is the Modified Vaccinia virus Ankara expressing Multiple epitopes and thrombospondin related adhesion protein.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Group 1 will receive ChAd63-METRAP at the dose of 5x10^8 vp i.v. Receives: Biological: ChAd63-METRAP |
| Group 2 | Experimental | Group 2 will receive ChAd63-METRAP at the dose of 5x10^9 vp i.v. Receives: Biological: ChAd63-METRAP |
| Group 3 | Experimental | Group 3 will receive ChAd63-METRAP at the dose of 5x10^10 vp i.v. Receives: Biological: ChAd63-METRAP |
| Group 4 | Experimental | Group 4 will receive ChAd63-METRAP at the dose of 5x10^10 vp s.c. Receives: Biological: ChAd63-METRAP |
| Group 5 | Experimental | Group 5 will receive ChAd63-METRAP at the dose of 2x10^11 vp s.c. Receives: Biological: ChAd63-METRAP |
| Group 6 | Experimental | Group 6 will receive MVA METRAP at the dose of 2 x 10^6 pfu i.v. Receives: Biological: MVA ME-TRAP |
| Group 7 | Experimental | Group 7 will receive MVA METRAP at the dose of 2 x 10^7 pfu i.v. Receives: Biological: MVA ME-TRAP |
| Group 8 | Experimental | Group 8 will receive MVA METRAP at the dose of 2 x 10^8 pfu i.v. Receives: Biological: MVA ME-TRAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of occurrence of emergent adverse events related to subcutaneous and intravenous administration of ChAd63 ME-TRAP and MVA ME-TRAP in healthy malaria-naïve volunteers
The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events (including solicited local or systemic reactogenicity signs and symptoms for 7 days following the vaccination; occurrence of unsolicited adverse events for 28 days following vaccination, and the occurrence of serious adverse events throughout the 3 month study duration).
Measured: 3 months
Secondary outcomes (2)
Identify potential biomarkers of vaccine deposition in the liver (biomolecules measured will include: liver enzymes and plasma cytokine levels).
Changes in potential biomarkers before and after vaccination will be assessed to identify markers biologically consistent with hepatocyte perturbation and inflammation. Some of the methodology will include: clotting assays (e.g. D-dimer levels), peripheral blood gene transcriptional profiling and some exploratory proteomic analysis of urine and plasma.
Measured: 3 months
Assess changes in immune response before and after vaccination using exploratory immunological assays.
Measures of immunogenicity generated in malaria naïve individuals of subcutaneous and intravenous administration of ChAd63 ME-TRAP, may include: ELISPOT (to enumerate IFN-γ producing T cells), flow cytometry and intracellular cytokine staining (to enumerate and functionally characterise immune cell populations such as T cells (e.g. CD4+ and CD8+) and B cells) and possibly gene expression profiling.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2017
- Study start28 Mar 2017
- Primary completion6 Jul 2020
- Study completion6 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Adrian V Hill, DPhill FRCP, Principal investigator, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03084289
- Sponsor's protocol ID
- VAC064
- Status last verified
- Aug 2020
- First submitted
- 3 Mar 2017
- Last updated
- 9 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Assess the Safety and Immunogenicity of Novel Routes of Administration of Plasmodium Falciparum Malaria Vaccine Candidates ChAd63 and MVA Encoding ME-TRAP.
- ClinicalTrials.gov ID
- NCT03084289
- Acronym / sponsor ID
- VAC064
- Conditions
- Malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 28 Mar 2017 (actual)
- Primary completion
- 6 Jul 2020 (actual)
- Study completion
- 6 Jul 2020 (actual)
- First posted
- 20 Mar 2017 (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.
The purpose of this study is to assess the safety and immunogenicity of novel routes of administration of the candidate malaria vaccines ChAd63 encoding ME-TRAP and MVA encoding ME-TRAP.
30-33 Healthy adult volunteers will be recruited in Oxford.
All vaccinations will be administered intravenously or subcutaneously. Each volunteer will receive a single vaccination of ChAd63 ME-TRAP or MVA ME-TRAP at different doses depending on the group.
Detailed description
Group1 consists of 3 volunteers receiving i.v. ChAd63 ME-TRAP at the dose of 5x10^8 vp.
Group 2 consists of 3 volunteers receiving i.v. ChAd63 ME-TRAP at the dose of 5x10^9 vp.
Group 3 consists of 9 volunteers receiving i.v. ChAd63 ME-TRAP at the dose of 5x10^10vp.
Group 4 consists of 3 volunteers receiving s.c. ChAd63 ME-TRAP at the dose of 5x10^10 vp.
Group 5 consists of 3 volunteers receiving s.c. ChAd63 ME-TRAP at the dose of 2x10^11 vp.
Group 6 consists of 3 volunteers receiving i.v. MVA ME-TRAP at the dose of 2x10^6 pfu.
Group 7 consists of 3 volunteers receiving i.v. MVA ME-TRAP at the dose of 2x10^7 pfu.
Group 8 consists of 3-6 volunteers receiving i.v. MVA ME-TRAP at the dose of 2x10^8 pfu.
The first Group 1 volunteer to receive intravenous ChAd63 ME-TRAP will be vaccinated alone. Safety data for the first 72 hours following vaccination must be satisfactorily reviewed before the remaining group 1 volunteers are vaccinated. The safety data for the first 72 hours following vaccination for all the volunteers in the group will again be reviewed before the first volunteer in the higher dose group 2 is vaccinated. Safety data for the first 72 hours following vaccination of this volunteer must be satisfactorily reviewed before the remaining group 2 volunteers are vaccinated. Similarly the safety data for the first 72 hours following vaccination for all the volunteers in this group will again be reviewed before the first volunteer in the higher dose group 3 is vaccinated. Once there is satisfactory review of the safety data of the first 72 hours post vaccination for this volunteer, the remaining group 3 volunteers will be enrolled to receive IV vaccination.
An identical process will be followed for the enrolment of groups 6 - 8 receiving MVA ME-TRAP intravenously. Once three group 8 volunteers have received vaccination and there has been a satisfactory safety review at 72 hours, the chief investigator will make a decision as to whether or not to enrol the final three volunteers on the basis of the immunology data - and whether further determination of immunogenicity is needed.
In parallel with Group 1, the first Group 4 volunteer to receive subcutaneous Chad63 ME-TRAP will be vaccinated alone. Safety data for the first 72 hours following vaccination must be satisfactorily reviewed before the remaining group 4 volunteers are vaccinated. The safety data for the first 72 hours following vaccination for all the volunteers in the group will again be reviewed before the first volunteer in the higher dose group 5 is vaccinated. Once there is satisfactory review of the safety data of the first 72 hours post vaccination for this volunteer, the remaining group 5 volunteers will be enrolled to receive SC vaccination.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: ChAd63-METRAPGroup 1 will receive ChAd63-METRAP at the dose of 5x10^8 vp i.v. |
| Group 2 | Experimental | Biological: ChAd63-METRAPGroup 2 will receive ChAd63-METRAP at the dose of 5x10^9 vp i.v. |
| Group 3 | Experimental | Biological: ChAd63-METRAPGroup 3 will receive ChAd63-METRAP at the dose of 5x10^10 vp i.v. |
| Group 4 | Experimental | Biological: ChAd63-METRAPGroup 4 will receive ChAd63-METRAP at the dose of 5x10^10 vp s.c. |
| Group 5 | Experimental | Biological: ChAd63-METRAPGroup 5 will receive ChAd63-METRAP at the dose of 2x10^11 vp s.c. |
| Group 6 | Experimental | Biological: MVA ME-TRAPGroup 6 will receive MVA METRAP at the dose of 2 x 10^6 pfu i.v. |
| Group 7 | Experimental | Biological: MVA ME-TRAPGroup 7 will receive MVA METRAP at the dose of 2 x 10^7 pfu i.v. |
| Group 8 | Experimental | Biological: MVA ME-TRAPGroup 8 will receive MVA METRAP at the dose of 2 x 10^8 pfu i.v. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 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
- 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 vaccination
- Agreement to refrain from blood donation during the course of the study
Key exclusion criteria (21 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.
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
- 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
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-METRAPThe candidate vaccine applicable to the clinical trial is the Chimpanzee adenovirus 63 expressing Multiple epitopes and thrombospondin related adhesion protein. | Biological | Group 1, Group 2, Group 3, Group 4, Group 5 |
| MVA ME-TRAPThe candidate vaccine applicable to the clinical trial is the Modified Vaccinia virus Ankara expressing Multiple epitopes and thrombospondin related adhesion protein. | Biological | Group 6, Group 7, Group 8 |
Primary outcome
Incidence of occurrence of emergent adverse events related to subcutaneous and intravenous administration of ChAd63 ME-TRAP and MVA ME-TRAP in healthy malaria-naïve volunteers
Time frame: 3 months
The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events (including solicited local or systemic reactogenicity signs and symptoms for 7 days following the vaccination; occurrence of unsolicited adverse events for 28 days following vaccination, and the occurrence of serious adverse events throughout the 3 month study duration).
2 secondary outcomes
Identify potential biomarkers of vaccine deposition in the liver (biomolecules measured will include: liver enzymes and plasma cytokine levels).
Time frame: 3 months
Assess changes in immune response before and after vaccination using exploratory immunological assays.
Time frame: 3 months
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 9 Oct 2020.
- Individual participant dataSharing planned: No
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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 Hill, DPhill FRCP principal investigator
Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ChAd63-METRAP and MVA ME-TRAP in people with 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 6 inclusion and 21 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 9 Oct 2020. 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 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.
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?
Incidence of occurrence of emergent adverse events related to subcutaneous and intravenous administration of ChAd63 ME-TRAP and MVA ME-TRAP in healthy malaria-naïve volunteers (time frame: 3 months). 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 9 Oct 2020.