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

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00984763
• Other study ID #: VAC035
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 24, 2009
• Last updated: May 27, 2015
• Start date: January 2010
• Est. completion date: September 2010

Study information

• Verified date: May 2015
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

Other known NCT identifiers

• NCT00605462

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

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)

Locations

Country	Name	City	State
United Kingdom	Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford	Oxford, Headington

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To demonstrate a correlation between in vitro growth inhibition assay and parasite multiplication rate in vivo		Up to 16 days following blood stage parasite challenge	No
Secondary	To detect differences in the multiplication rate responses between unvaccinated control subjects and volunteers vaccinated with AMA1-C1/Alhydrogel® + CPG 7909		Up to 16 days following blood stage parasite challenge	No