A Phase Ia Clinical Trial to Assess the Safety and Immunogenicity of New Plasmodium Falciparum Malaria Vaccine Candidates ChAd63 RH5 Alone and With MVA RH5

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT02181088

Collaborator

European Commission (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess two new malaria vaccines, ChAd63 RH5 and MVA RH5, at different doses and alone or in combination. The study will enable us to assess the safety of the vaccines and the extent of the immune response in healthy volunteers. We will do this by giving volunteers one or two vaccinations, doing blood tests and collecting information about any symptoms that occur after vaccination. This is the first trial to use these vaccines in humans.

Condition or Disease	Intervention/Treatment	Phase
Malaria Plasmodium Falciparum	Biological: ChAd63 RH5 low dose Biological: ChAd63 RH5 full dose Biological: MVA RH5 low dose Biological: MVA RH5 full dose	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Phase Ia Clinical Trial to Assess the Safety and Immunogenicity of New Plasmodium Falciparum Malaria Vaccine Candidates ChAd63 RH5 Alone and With MVA RH5

Study Start Date :

Aug 1, 2014

Actual Primary Completion Date :

Oct 1, 2015

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 (ChAd63 RH5 low dose) 1 dose of ChAd63 RH5 5 x 10^9 vp intramuscularly	Biological: ChAd63 RH5 low dose ChAd63 RH5 at 5 x 10^9 vp Other Names: ChAd63 RH5
Experimental: Group 2A (ChAd63 RH5 full dose) 1 dose of ChAd63 RH5 at 5 x 10^10 vp intramuscularly	Biological: ChAd63 RH5 full dose ChAd63 RH5 at 5 x 10^10 vp Other Names: ChAd63 RH5
Experimental: Group 2B (ChAd63 RH5 full dose and MVA RH5 low dose) 1 dose of ChAd63 RH5 at 5 x 10^10 vp intramuscularly and 1 dose MVA RH5 at 1 x 10^8 pfu 8 weeks later intramuscularly	Biological: ChAd63 RH5 full dose ChAd63 RH5 at 5 x 10^10 vp Other Names: ChAd63 RH5 Biological: MVA RH5 low dose MVA RH5 at 1 x 10^8 pfu Other Names: MVA RH5
Experimental: Group 2C (ChAd63 RH5 full dose and MVA RH5 full dose) 1 dose of ChAd63 RH5 at 5 x 10^10 vp intramuscularly and 1 dose MVA RH5 at 2 x 10^8 pfu 8 weeks later intramuscularly	Biological: ChAd63 RH5 full dose ChAd63 RH5 at 5 x 10^10 vp Other Names: ChAd63 RH5 Biological: MVA RH5 full dose MVA RH5 at 2 x 10^8 pfu Other Names: MVA RH5

Outcome Measures

Primary Outcome Measures

To assess the safety of ChAd63 RH5 when administered alone and in heterologous prime-boost with MVA RH5 [240 days]
Occurrence of solicited and unsolicited adverse events will be monitored at each clinic visit from diary cards, clinical review, clinical examination (including observations) and laboratory results.

Secondary Outcome Measures

To assess the cellular and humoral immunogenicity of ChAd63 RH5 when administered alone, and in heterologous prime-boost with MVA RH5 in healthy volunteers. [240 days]
P. falciparum RH5-specific immunogenicity will be assessed by a variety of immunological assays. These may include ex vivo ELISpot assays for interferon gamma and flow cytometry assays, as well as antibody ELISAs, functional antibody assays and B cell analyses. Other exploratory immunological assays including cytokine analysis, other antibody assays, anti-adenovirus antibodies, DNA analysis of genetic polymorphisms potentially relevant to vaccine immunogenicity and gene expression studies amongst others may be performed at the discretion of the Investigators.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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 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

Exclusion Criteria:

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 malaria vaccine or any other 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 human immunodeficiency virus (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, e.g. egg products.
Any history of anaphylaxis in reaction 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
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 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 general practitioner (GP) to confirm medical history and safety to participate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford	Oxford		United Kingdom	OX3 7LE
2	Wellcome Trust CRF, Southampton General Hospital, University of Southampton	Southampton		United Kingdom