MalariaPhase 1/2NCT03203421
A Safety and Efficacy Study of ChAdOx1 LS2 and MVA LS2
A Phase 1/2 study testing ChAdOx1 LS2 and MVA LS2 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, immunogenicity and efficacy of the candidate malaria vaccines ChAdOx1 LS2 and MVA LS2. Healthy adult volunteers will be recruited and vaccinated in Oxford. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- ChAdOx1 LS2 and MVA LS2
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Jul 2017to 20 Dec 2017
- 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
- 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 to participate in the trial.
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- Additional inclusion criteria for group 2 and control groups A\&B:
- 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.
- 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.
Who cannot join
- History of clinical malaria (any species).
- Travel to a clearly malaria endemic locality during the study period or within the preceding six months
- Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data as assessed by the investigator. This may include non-malaria adenovirus vectored experimental vaccine. If any volunteers in Group 2 undergo rechallenge, this exclusion criterion does not extend to the vaccines previously received in the VAC067 trial.
- 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).
- Use of immunoglobulins or blood products within 3 months prior to enrolment.
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- 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.
- Pregnancy, lactation or 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 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 standard UK units every week.
- Suspected or known injecting drug abuse in the 5 years preceding enrolment.
- Hepatitis B surface antigen (HBsAg) detected in serum.
- 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).
- Inability of the study team to contact the volunteer's GP to confirm medical history and safety to participate
- Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested (described in section 9.6.1).
- 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.
- Additional exclusion criteria for group 2 and control groups A\&B:
- Clinically significant disturbances of electrolyte balance, eg, hypokalaemia or hypomagnesaemia
- 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 sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
- 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 and existing contraindication to the use of Malarone.
- Family history of congenital QT prolongation or sudden death and existing contraindication to the use of Malarone.
- History of cardiac arrhythmia, including clinically relevant bradycardia and existing contraindication to the use of Malarone.
- Positive family history in both 1st and 2nd degree relatives < 50 years old for cardiac disease.
- Volunteer unable to be closely followed for social, geographic or psychological reason.
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 Phase I/II Study to Assess the Safety, Immunogenicity and Protective Efficacy of Novel Malaria Vaccine Candidates ChAdOx1 LS2 and MVA LS2 in Healthy UK Adults
The purpose of this study is to assess the safety, immunogenicity and efficacy of the candidate malaria vaccines ChAdOx1 LS2 and MVA LS2.
Healthy adult volunteers will be recruited and vaccinated in Oxford.
Read the detailed description
This is an open label, dose-escalation, first in human, partially blinded, phase I/IIa controlled human malaria infection (CHMI) study. The study will assess the safety, immunogenicity and protective efficacy of the novel malaria vaccine candidates ChAdOx1 LS2 and MVA LS2 in healthy UK adults.
Healthy, malaria naive adults, aged between 18 and 45 years, will be recruited and vaccinated in Oxford.
A total of between 23 and 31 volunteers will be recruited across four groups:
Group 1 volunteers will receive a low dose ChAdOx1 LS2 vaccination on day 0. Group 2 volunteers will receive a high dose ChAdOx1 LS2 vaccination on day 0 and a dose of MVA LS2 on day 56, followed by a CHMI on day 77. Volunteers exhibiting sterile protection will undergo a repeat CHMI 5-7 months later.
Control Group A will not receive any vaccinations and will undergo CHMI on day 77.
Control Group B will not receive any vaccinations and will undergo CHMI during the repeat challenge.
- Conditions
- Malaria
- Being tested
- ChAdOx1 LS2, MVA LS2
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChAdOx1 LS2Biological
A viral vectored vaccine, using a chimpanzee adenovirus as a vector encoding malaria liver-stage dual antigen LS2 (LSA1 and LSAP2) fused with the transmembrane domain from shark invariant chain.
MVA LS2Biological
Modified vaccinia Ankara vector encoding liver-stage dual antigen LS2 (LSA1 ad LSAP2) fused to the C-terminal end of the leader sequence of tPA.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose (Group 1) | Active comparator | One low dose of ChAdOx1 LS2 (5 x 10^9 vp) on day 0. Receives: Biological: ChAdOx1 LS2 |
| Prime-Boost (Group 2) | Active comparator | One high dose of ChAdOx1 LS2 (2.5 x 10^10 vp) on day 0 and one dose of MVA LS2 (2 x 10^8 pfu) on day 56. Receives: Biological: ChAdOx1 LS2; Biological: MVA LS2 |
| Control Group A | No intervention | No vaccinations will be administered. |
| Control Group B | No intervention | No vaccinations will be administered. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety and tolerability of ChAdOx1 LS2 administered alone and with MVA LS2 in a prime-boost vaccination regimen in healthy malaria-naive volunteers assessed by the frequency and severity of adverse events.
The number of participants who experience adverse events and the severity of any adverse events.
Measured: 31 - 40 weeks
The efficacy of ChAdOx2 LS2 and MVA LS2 administered in a prime-boost vaccination regimen against malaria sporozoite challenge, in healthy malaria-naive volunteers.
The occurrence of Plasmodium falciparum parasitemia, assessed by blood slide and polymerase chain reaction (PCR).
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2017
- Study start3 Jul 2017
- Primary completion20 Dec 2017
- Study completion20 Dec 2017
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 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03203421
- Sponsor's protocol ID
- VAC067
- Status last verified
- Aug 2017
- First submitted
- 27 Jun 2017
- Last updated
- 13 Jun 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Silman D, Flaxman A, Datoo M, Edwards NJ, Ramos-Lopez F, Mitton C, Mair C, Bellamy D, Bowyer G, Morter R, Halbroth B, Venkatraman N, Folegatti PM, Marshall J, Poulton I, Bajer A, Salman AM, Berrie E, Baum J, Blagborough AM, Crocker W, Roberts R, Lawrie AM, Spencer AJ, Gilbert SC, Ewer KJ, Hill AVS. Phase I/IIa study to assess the safety, immunogenicity and efficacy of ChAdOx1-MVA vectored vaccines expressing a novel liver-stage malaria dual antigen LS2 by sporozoite challenge in malaria-naive adults. Wellcome Open Res. 2026 Apr 6;9:734. doi: 10.12688/wellcomeopenres.22900.2. eCollection 2024.
PubMed 41970240
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study to Assess the Safety, Immunogenicity and Protective Efficacy of Novel Malaria Vaccine Candidates ChAdOx1 LS2 and MVA LS2 in Healthy UK Adults
- ClinicalTrials.gov ID
- NCT03203421
- Acronym / sponsor ID
- VAC067
- Conditions
- Malaria
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 3 Jul 2017 (actual)
- Primary completion
- 20 Dec 2017 (actual)
- Study completion
- 20 Dec 2017 (actual)
- First posted
- 29 Jun 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, immunogenicity and efficacy of the candidate malaria vaccines ChAdOx1 LS2 and MVA LS2.
Healthy adult volunteers will be recruited and vaccinated in Oxford.
Detailed description
This is an open label, dose-escalation, first in human, partially blinded, phase I/IIa controlled human malaria infection (CHMI) study. The study will assess the safety, immunogenicity and protective efficacy of the novel malaria vaccine candidates ChAdOx1 LS2 and MVA LS2 in healthy UK adults.
Healthy, malaria naive adults, aged between 18 and 45 years, will be recruited and vaccinated in Oxford.
A total of between 23 and 31 volunteers will be recruited across four groups:
Group 1 volunteers will receive a low dose ChAdOx1 LS2 vaccination on day 0. Group 2 volunteers will receive a high dose ChAdOx1 LS2 vaccination on day 0 and a dose of MVA LS2 on day 56, followed by a CHMI on day 77. Volunteers exhibiting sterile protection will undergo a repeat CHMI 5-7 months later.
Control Group A will not receive any vaccinations and will undergo CHMI on day 77.
Control Group B will not receive any vaccinations and will undergo CHMI during the repeat challenge.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low Dose (Group 1) | Active comparator | Biological: ChAdOx1 LS2One low dose of ChAdOx1 LS2 (5 x 10^9 vp) on day 0. |
| Prime-Boost (Group 2) | Active comparator | Biological: ChAdOx1 LS2, Biological: MVA LS2One high dose of ChAdOx1 LS2 (2.5 x 10^10 vp) on day 0 and one dose of MVA LS2 (2 x 10^8 pfu) on day 56. |
| Control Group A | No intervention | –No vaccinations will be administered. |
| Control Group B | No intervention | –No vaccinations will be administered. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 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
- 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 (32 listed)
- History of clinical malaria (any species).
- Travel to a clearly malaria endemic locality during the study period or within the preceding six months
- Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data as assessed by the investigator. This may include non-malaria adenovirus vectored experimental vaccine. If any volunteers in Group 2 undergo rechallenge, this exclusion criterion does not extend to the vaccines previously received in the VAC067 trial.
- 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).
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 |
|---|---|---|
| ChAdOx1 LS2A viral vectored vaccine, using a chimpanzee adenovirus as a vector encoding malaria liver-stage dual antigen LS2 (LSA1 and LSAP2) fused with the transmembrane domain from shark invariant chain. | Biological | Low Dose (Group 1), Prime-Boost (Group 2) |
| MVA LS2Modified vaccinia Ankara vector encoding liver-stage dual antigen LS2 (LSA1 ad LSAP2) fused to the C-terminal end of the leader sequence of tPA. | Biological | Prime-Boost (Group 2) |
Primary outcome
The safety and tolerability of ChAdOx1 LS2 administered alone and with MVA LS2 in a prime-boost vaccination regimen in healthy malaria-naive volunteers assessed by the frequency and severity of adverse events.
Time frame: 31 - 40 weeks
The number of participants who experience adverse events and the severity of any adverse events.
The efficacy of ChAdOx2 LS2 and MVA LS2 administered in a prime-boost vaccination regimen against malaria sporozoite challenge, in healthy malaria-naive volunteers.
Time frame: 90 days
The occurrence of Plasmodium falciparum parasitemia, assessed by blood slide and polymerase chain reaction (PCR).
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 13 Jun 2018.
- Derived from this study: PubMed 41970240Silman D, Flaxman A, Datoo M, Edwards NJ, Ramos-Lopez F, Mitton C, Mair C, Bellamy D, Bowyer G, Morter R, Halbroth B, Venkatraman N, Folegatti PM, Marshall J, Poulton I, Bajer A, Salman AM, Berrie E, Baum J, Blagborough AM, Crocker W, Roberts R, Lawrie AM, Spencer AJ, Gilbert SC, Ewer KJ, Hill AVS. Phase I/IIa study to assess the safety, immunogenicity and efficacy of ChAdOx1-MVA vectored vaccines expressing a novel liver-stage malaria dual antigen LS2 by sporozoite challenge in malaria-naive adults. Wellcome Open Res. 2026 Apr 6;9:734. doi: 10.12688/wellcomeopenres.22900.2. eCollection 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 ChAdOx1 LS2 and MVA LS2 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 12 inclusion and 32 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 13 Jun 2018. 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 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 safety and tolerability of ChAdOx1 LS2 administered alone and with MVA LS2 in a prime-boost vaccination regimen in healthy malaria-naive volunteers assessed by the frequency and severity of adverse events. (time frame: 31 - 40 weeks). 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 NCT03203421, 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 13 Jun 2018.