A Study to Assess Safety, Immunogenicity and Parasite Growth Inhibition of an Asexual Blood Stage Vaccine for P. Falciparum Malaria

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00984763
First received: September 24, 2009
Last updated: March 25, 2011
Last verified: March 2011
  Purpose

Malaria is a parasite, infection with which kills over 2 million people each year. It is a major problem for those who live in endemic areas and for travellers. There is a great need for a safe effective malaria vaccine. The purpose of this study is to examine a new vaccine designed to provide immunity during the blood stage of the malaria parasite's lifecycle.

The vaccine consists of AMA1-C1 which is a mixture of two recombinant synthetic AMA1 proteins from two Plasmodium falciparum strains, Alhydrogel® which is an aluminium-based adjuvant and CPG 7909 - an oligodeoxynucleotide, which enhances immune response.

This study will enable the investigators to assess:

  1. The ability of of a growth inhibition assay to predict the effectiveness of a malaria vaccine.
  2. The safety of the vaccine in healthy volunteers
  3. The response of the human immune system to the vaccine

Condition Intervention Phase
Malaria
Biological: AMA1-C1/Alhydrogel® + CPG 7909
Biological: Control
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase I/IIa Study of the Safety, Immunogenicity and Parasite Growth Inhibitory Activity of AMA1-C1/Alhydrogel® + CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • To demonstrate a correlation between in vitro growth inhibition assay and parasite multiplication rate in vivo [ Time Frame: Up to 16 days following blood stage parasite challenge ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To detect differences in the multiplication rate responses between unvaccinated control subjects and volunteers vaccinated with AMA1-C1/Alhydrogel® + CPG 7909 [ Time Frame: Up to 16 days following blood stage parasite challenge ] [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: January 2010
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
AMA1-C1/Alhydrogel® + CPG 7909 vaccine given twice two months apart followed by malaria parasite challenge
Biological: AMA1-C1/Alhydrogel® + CPG 7909
A 0.55 mL dose of AMA1-C1/Alhydrogel® + CPG 7909 (corresponds to 80 µg of AMA1-C1 and 564 µg of CPG 7909)
No Intervention: Group 2
Control: malaria parasite challenge without prior vaccinations
Biological: Control
No intervention

  Eligibility

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

Inclusion Criteria:

  • Subject is willing and able to give informed consent for participation in the study
  • Healthy, non pregnant adult aged 18 - 50 years
  • Resident in or near Oxford for the duration of the challenge study
  • Seropositive for CMV and EBV
  • Female subjects of child bearing potential must be willing to ensure that they practice effective contraception during the study
  • Males must be willing to use barrier contraception from day of first vaccination onwards until 3 months after the second vaccination
  • Able (in the Investigator's opinion) and willing to comply with all study requirements
  • Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study
  • Agreement to permanently refrain from blood donation.

Exclusion Criteria:

  • Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis as defined in Appendix B
  • Female patient/subject who is pregnant, lactating or planning pregnancy during the course of the study
  • Healthy volunteers who have participated in another research study involving an investigational product in the past 12 weeks
  • Subjects who have previously received an investigational malaria vaccine
  • History of malaria chemoprophylaxis with chloroquine within 5 months prior to the planned challenge, with Lariam within 6 weeks prior to the challenge, and Riamet® within 2 weeks prior to the challenge
  • Travel to a malaria endemic area within the previous 6 months
  • Planned travel to malarious areas during the study period
  • Any history of malaria
  • Contraindication to both anti-malarial drugs (Riamet® and chloroquine)
  • concomitant use of other drugs known to cause QT-interval prolongation, ( e.g. macrolides, quinolones, amiodarone etc)
  • An estimated ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system (Conroy 2003)
  • Family history of sudden cardiac death
  • History of cardiac arrhythmia or prolonged QT syndrome
  • Any history of severe allergic reaction or anaphylaxis
  • History of a known allergy to nickel
  • 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
  • History or evidence of pre-existing autoimmune or antibody mediated disease or laboratory evidence of possible autoimmune disease (defined as anti-dsDNA ≥ 25 IU/mL)
  • Seropositive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus
  • Any on-going chronic illness requiring hospital specialist supervision
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
  • History of or current intravenous drug abuse
  • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
  • Any other significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject's ability to participate in the study.
  • Investigator assessment of lack of willingness to participate and comply with all requirements of the protocol
  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: NCT00984763

Locations
United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford
Oxford, Headington, United Kingdom
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Adrian VS Hill, D.Phil, FRCP University of Oxford
  More Information

No publications provided by University of Oxford

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Professor Adrian VS Hill, Centre for Clinical Vaccinology and Tropical Medicine University of Oxford
ClinicalTrials.gov Identifier: NCT00984763     History of Changes
Obsolete Identifiers: NCT00605462
Other Study ID Numbers: VAC035
Study First Received: September 24, 2009
Last Updated: March 25, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:
Malaria
Vaccine

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Aluminum Hydroxide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014