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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Malaria
- Sponsor
- University of Oxford
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- The efficacy of ChAdOx2 LS2 and MVA LS2 administered in a prime-boost vaccination regimen against malaria sporozoite challenge, in healthy malaria-naive volunteers.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief 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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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.
Exclusion Criteria
- •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.
- •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.
Outcomes
Primary Outcomes
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).
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.