Clinical Trial for Malaria Vaccines to Test for Safety, Immune Response and Protection Against Malaria (DNA-Ad)
|Malaria||Biological: DNA vaccine prime Biological: adenovirus type 5 vaccine boost||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Prevention
|Official Title:||Clinical Trial on Safety, Immunogenicity, and Efficacy of a Prime Boost Regimen of DNA- and Adenovirus-vectored Malaria Vaccines Encoding Plasmodium Falciparum Circumsporozoite Protein and Apical Membrane Antigen 1 in Healthy Malaria-Naïve Adults in the US|
- Number of adverse events [ Time Frame: 5 years ]
The vaccine will be considered safe and well-tolerated if there are no severe or serious adverse events (AE) related to vaccine administration or if any severe events are relatively benign (e.g.
erythema meeting criteria for severe due to its dimensions but not significantly affecting the activities of daily living for the subject) or brief in duration (e.g. less than 48 hours). The AEs will be assessed according to the method below.
- Occurrence, severity, and duration of any solicited symptoms starting on the day of immunization through day 7 after each immunization
- Occurrence of any unsolicited symptoms, abnormal physical findings, and laboratory values starting from the day of immunization through day 28 after each immunization
- Occurrence of any serious adverse events, as defined in 21 CFR 312.32, during the five-year study period
- Number of sterile or partial protections [ Time Frame: 28 days after malaria challenge ]The DNA-Ad vaccine is considered efficacious if it offers any degree of sterile or partial protection that reaches statistical significance (p<0.05). The vaccine efficacy will be determined by two parameters: 1) sterile protection for 28 days after challenge, 2) partial protection as determined by delay to parasitemia by smears and PCR.
- Number of humoral immunity expressions [ Time Frame: 28 days after malaria challenge ]The DNA-Ad vaccine is considered to confer humoral immunity if the increase of antibody response for CSP or AMA1 by ELISA post immunization is statistically significant (p<0.05) compared to the levels before immunization.
- Number of cellular immunity expressions [ Time Frame: 28 days after malaria challenge ]The DNA-Ad vaccine is considered to confer cellular immunity if a positive ELISpot response is detected after immunization
|Study Start Date:||May 2009|
|Estimated Study Completion Date:||November 2018|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
DNA vaccine prime
Biological: DNA vaccine prime
2 mg total dose (1 mg per construct in a volume of 1 mL)
adenovirus type 5 vaccine boost
Biological: adenovirus type 5 vaccine boost
2 x 1010 particle units (pu) (1 x 1010 pu per each of 2 constructs including CSP and AMA1 respectively)
The goal of this study is to evaluate if the DNA-Ad vaccine that targets both the liver and blood stages of the malaria life cycle is safe and protective, in hopes to develop a vaccine to prevent infection and/or lessen the severity of disease caused by the P. falciparum malaria parasite. More specifically, this DNA-Ad vaccine contains a liver stage antigen (circumsporozoite protein) and an antigen (apical membrane antigen 1) that is present in both the liver and blood stages designed to prevent infection by killing the majority of developing parasites in the liver and to prevent severe disease and death should break-through blood stage infections occur.
This study is an open-label, Phase 1/2a study designed to assess the safety, immunogenicity, and efficacy of a DNA-Ad vaccine in healthy adults who are Ad5 seropositive or seronegative. The vaccinated study group will consist of up to 20 healthy, malaria-naïve adults aged 18 to 50 years, who have been previously screened to meet inclusion and exclusion criteria and will receive three priming doses of the DNA vaccine and a single dose of the boosting component, an adenovirus-vectored vaccine to be given 4 months after the last dose of DNA. Follow up visits will occur after each immunization. The control group will consist of six non-immunized subjects that will participate in a challenge to assure that vaccinated subjects were indeed exposed to P. falciparum. Subjects in both the immunized and control cohorts will receive malaria challenge. Subjects will be assessed for development of parasitemia by daily blood smears and will be closely observed in hotel after the challenge. Subjects will then be followed periodically and have the final in-person visit twelve weeks after the challenge, followed by annual contact by phone, email, or mailings up to five years after the first dose of immunization per FDA recommendation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00870987
|United States, Maryland|
|Clinical Trials Center, WRAIR|
|Silver Spring, Maryland, United States, 20910|
|Principal Investigator:||Judith Epstein, MD||US Military Vaccine Program, NMRC PI, Naval Officer|