NCT00371189

Adenovirus Vaccine for Malaria

A Phase I Randomized, Controlled, Dosage-Escalation Trial to Evaluate the Immunogenicity, Safety, and Reactogenicity of an Adenovirus Type 35 Based Circumsporozoite Malaria Vaccine in Healthy Adults 18 to 45 Years of Age

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 75 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

Malaria is caused by a parasite carried by a mosquito. Currently, there is no vaccine licensed to prevent malaria. The purpose of this study is to find the most effective and safest dose of an experimental vaccine for the treatment of malaria. Participants will include 72 healthy adults, ages18 to 45, enrolled at Vanderbilt University Medical Center and Stanford University. Volunteers will receive 3 doses of either the malaria vaccine or placebo (contains no vaccine) by injection into a muscle at 0, 1 and 6 months. Investigators will evaluate how the body responds to increasing dosage strengths of the vaccine. Study procedures include physical exam, multiple blood draws, and completion of a memory aid (diary). Each participant will be actively involved in the study for about 12 months. Then, an annual phone call will be made to check for any serious illness events for a period of 5 years.

Detailed description

Malaria currently represents one of the most prevalent infections in tropical and subtropical areas throughout the world. Each year, malaria affects around 300 million people and kills 1 to 3 million people in developing countries. The widespread occurrence and the growing incidence of malaria are a consequence of the increasing numbers of drug-resistant parasites and insecticide-resistant parasite vectors. Other factors include environmental and climatic changes, civil disturbances and increased mobility of populations. It is hypothesized that the Ad35.CS.01 vaccine will prevent the Plasmodium (P.) falciparum parasite, which causes malaria, from entering and developing within the liver of those who become infected. Ad35.CS.01 would therefore be expected to reduce malaria-attributable morbidity and mortality. The purpose of this phase I, randomized, controlled, dosage-escalation trial is to evaluate the immunogenicity, safety, and reactogenicity of an Adenovirus Type 35 based circumsporozoite malaria vaccine in 72 healthy adults, 18 to 45 years of age, in the United States. Subjects will be randomized in a 5:1 ratio to receive 3 doses of the Adenovirus Type 35 circumsporozoite malaria vaccine (Ad35.CS.01) or normal saline placebo control by the intramuscular route at 0, 1 and 6 months. The safety, reactogenicity, and immunogenicity of ascending dosages of the vaccine will be assessed. Fifteen subjects will receive vaccine at each of the following dosage levels: 10\^8 viral particles (vp)/milliliters (ml), 10\^9 vp/ml, 10\^10 vp/ml and 10\^11 vp/ml with 3 subjects receiving control at each of these dosage levels. Dosage escalation will proceed only after review of the safety data by the Safety Monitoring Committee of the prior dosage level. The primary objective is to assess the safety and reactogenicity of ascending dosages of Adenovirus Type 35 based circumsporozoite malaria vaccine among healthy subjects given in 3 intramuscular doses at 0, 1 and 6 months. The secondary objective is to evaluate the immunogenicity of the Adenovirus Type 35 based circumsporozoite malaria vaccine through performance of Humoral Immune Assays \[ELISA (enzyme-linked immunosorbent assay)\] for antibodies to circumsporozoite antigen and Adenovirus Neutralization Assay for neutralizing antibodies to Adenovirus type 35) and Cellular Immune Assays \[enzyme-linked immunosorbent spot (ELISPOT) and Flow Cytometry\] for circumsporozoite (CS)-specific cluster of differentiation (CD)4+ and CD8+ T cell responses.

Conditions

• Plasmodium Falciparum Infection

Interventions

Type	Name	Description
DRUG	Placebo	Normal saline.
BIOLOGICAL	Ad35.CS.01 Circumsporozoite Malaria Vaccine	Adenovirus Type 35 Circumsporozoite Malaria Vaccine (Ad35.CS.01); administered at 0, 1, and 6 months; dosage levels: 10\^8 viral particles (vp)/mL, 10\^9 vp/mL, 10\^10 vp/mL and 10\^11 vp/mL.

Timeline

• Start date: 2007-01-01
• Primary completion: 2014-06-01
• Completion: 2014-06-01
• First posted: 2006-09-01
• Last updated: 2014-09-22

Locations

2 sites across 1 country: United States