Efficacy of Malaria Vaccines in Kenyan Adults

This study has been completed.
Sponsor:
Collaborator:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01666925
First received: August 14, 2012
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

Malaria transmission is falling in some parts of Africa as bed nets and anti-malarials become more widely available. However, transmission still persists and it appears that additional control measures are required. The leading malaria vaccine candidate in development is RTS,S which has efficacy against clinical malaria measured at 30-50% in the field. This partial protection might be enhanced by combination with other components. The other vaccination approach that has produced repeatable efficacy in humans is the use of viral vectors to induce T cell responses. Previous attempts with this vaccine approach have been effective in challenge studies in Oxford, but ineffective in the field, probably because of reduced immunogenicity.

Recently, studies in Oxford, Kenya and the Gambia have shown higher levels of immunogenicity by using a chimpanzee adenovirus (ChAd63) followed by an attenuated vaccinia virus (modified vaccinia Ankara) to deliver the pre-erythrocytic antigen, multiple epitope string with thrombospondin- related adhesion protein (ME-TRAP).

The increase in immunogenicity has lead to sterile protection in 3 out of 14 volunteers and partial protection in 5 out of 14 volunteers in challenge studies.

The investigators propose a Phase 2b study of 120 healthy adult men in Kenya. The investigators will assess the efficacy and further evaluate the immunogenicity and safety profile of the vaccine regimen. The investigators also intend to assess the correlates of efficacy and natural immunity.


Condition Intervention Phase
Malaria
Biological: ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation
Biological: Rabies vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Efficacy Study of ChAd63MVA ME-TRAP Prime-boost Vaccination Against Plasmodium Falciparum Infection.

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Vaccine Efficacy [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    The first episode of P.falciparum infection positive by PCR, for P.falciparum.


Secondary Outcome Measures:
  • Vaccine immunogenicity [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

    Measures of immunogenicity will include:

    Ex vivo ELISPOT responses to overlapping pools of ME - TRAP peptides. Cultured ELISPOT responses to overlapping pools of ME - TRAP peptides. ICS by flow cytometry for cell mediated immune responses ELISA for antibodies to malaria antigens


  • Reactogenicity [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    All solicited and unsolicited local and systemic vaccine- linked adverse events (AEs) including clinically significant laboratory abnormalities.


Enrollment: 120
Study Start Date: March 2012
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ChAd63 ME-TRAP and MVA ME-TRAP
ChAd63 ME-TRAP / MVA ME-TRAP heterologous prime-boost immunisation
Biological: ChAd63 ME-TRAP / MVA ME-TRAP prime-boost immunisation
ChAd63 ME-TRAP: 5 x 10^10vp MVA ME-TRAP: 2 x 10^8 pfu
Active Comparator: Rabies vaccine
2 x 2.5IU Verorab
Biological: Rabies vaccine
2 x 2.5IU Verorab
Other Name: Verorab

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Consenting adult males aged 18 - 50 years in good health.
  • Will remain resident in the study area for the study duration.
  • Able and willing (in the Investigator's opinion) to comply with all study requirements
  • Informed Consent

Exclusion Criteria:

  • Any significant medical 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
  • Hypersensitivity to Verorab, the trial vaccines or the antimalarial used.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, kathon, neomycin
  • History of splenectomy.
  • Haemoglobin less than 10.0 g/dl
  • Clinically significant abnormalities of laboratory screening tests (full blood count, ALT, creatinine levels).
  • Blood transfusion within the month preceding enrolment.
  • History of vaccination with previous experimental malaria vaccines or other vaccines likely to impact on findings of study (e.g. other MVA or adenovirus vectored vaccines)
  • Administration of any other vaccine or immunoglobulin within 2 weeks before vaccination.
  • HIV or Hepatitis B surface antigen seropositivity.
  • Current participation in another clinical trial or recent participation within 12 weeks of this study.
  • Any other finding which in the opinion of the investigators would increase the risk of an adverse outcome from participation in the trial.
  • Likelihood of travel away from the study area
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01666925

Locations
Kenya
KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research - Coast
Kilifi, Kenya, PO Box 230, 80108
Sponsors and Collaborators
University of Oxford
European and Developing Countries Clinical Trials Partnership (EDCTP)
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01666925     History of Changes
Other Study ID Numbers: VAC046
Study First Received: August 14, 2012
Last Updated: December 11, 2013
Health Authority: Republic of Kenya: Pharmacy and Poisons Board

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on September 16, 2014