Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Trial for Malaria Vaccines to Test for Safety, Immune Response and Protection Against Malaria (DNA-Ad)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00870987
Recruitment Status : Completed
First Posted : March 30, 2009
Last Update Posted : October 15, 2018
Sponsor:
Collaborators:
United States Agency for International Development (USAID)
Walter Reed Army Institute of Research (WRAIR)
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command

Tracking Information
First Submitted Date  ICMJE March 27, 2009
First Posted Date  ICMJE March 30, 2009
Last Update Posted Date October 15, 2018
Actual Study Start Date  ICMJE May 2009
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2015)
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.
  1. Occurrence, severity, and duration of any solicited symptoms starting on the day of immunization through day 7 after each immunization
  2. Occurrence of any unsolicited symptoms, abnormal physical findings, and laboratory values starting from the day of immunization through day 28 after each immunization
  3. Occurrence of any serious adverse events, as defined in 21 CFR 312.32, during the five-year study period
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2009)
Vaccine considered safe & well-tolerated if no SAEs related to vaccine administration or if any severe events are relatively benign or brief in duration (e.g. less than 48 hours), and the same event occurring in no more than 20% of the volunteers. [ Time Frame: 7 days after immunization ]
Change History Complete list of historical versions of study NCT00870987 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2015)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2009)
DNA-Ad vaccine is considered efficacious if it offers any degree of sterile or partial protection that reaches statistical significance. [ Time Frame: 28 days after challenge ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial for Malaria Vaccines to Test for Safety, Immune Response and Protection Against Malaria
Official Title  ICMJE 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
Brief Summary The purpose of this study is to test the safety and effectiveness of a new malaria vaccine, the DNA-Ad vaccine. The study is specifically looking at a vaccine regimen against Plasmodium falciparum, the most deadly form of malaria.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Malaria
Intervention  ICMJE
  • Biological: DNA vaccine prime
    2 mg total dose (1 mg per construct in a volume of 1 mL)
  • 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)
Study Arms
  • Experimental: 1
    DNA vaccine prime Given at 0, 4, and 8 weeks
    Intervention: Biological: DNA vaccine prime
  • Experimental: 2
    adenovirus type 5 vaccine boost Given at 24 weeks
    Intervention: Biological: adenovirus type 5 vaccine boost
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2018)
82
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2009)
26
Actual Study Completion Date July 2015
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy adults 18 to 50 years of age (inclusive)
  • Women who are not pregnant by a current negative pregnancy test or of non-childbearing potential
  • Willing to use an FDA approved birth control method including condoms, birth control pills, sterility surgery, or intrauterine devices among others, from time of enrollment until 6 months after the end of the active phase of the study
  • Able to provide free and willing written informed consent to participate
  • Score at least 80% correct on a 10 question Assessment of Understanding
  • No plans to travel to a malaria endemic area during the course of the study
  • Free of significant health problems as established by medical history and clinical examination completed prior to the study
  • Available to participate and reachable for duration of study (up to five years)
  • Only subjects with no or low cardiac risk factors according to the Gaziano study [53] and a normal EKG will be included in the study

Exclusion Criteria:

  • Pregnant (positive HCG) or nursing at screening or plans to become pregnant or nurse from the time of enrollment until 6 months after sporozoite challenge
  • Any past history of malaria
  • History of receipt of malaria vaccine
  • Plans to travel to malarious areas during the study period
  • Use of any investigational or non-registered drug or vaccine within 30 days prior to enrollment
  • Seropositive for HIV, hepatitis C virus (antibodies to HIV and HCV), and/or HBsAg
  • Subjects in the immunized group who engage in high-risk behaviors for acquiring HIV
  • Allergy to antimalarials or significant (e.g. systemic) hypersensitivity reactions to mosquito bites (local hypersensitivity reactions at the site of a mosquito bite are not an exclusion criterion)
  • History of psoriasis (given its interaction with chloroquine)
  • Use or planned use of any drugs with significant anti-malarial activity, such as doxycycline, clindamycin, azithromycin, or trimethoprim/sulfamethoxazole among others during the study period (subjects can withhold the use of these medications during the study period if approved by their primary care physicians, at the minimum starting from four weeks before vaccine administration until four weeks after becoming parasitemic) Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection and history of splenectomy
  • Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of challenge
  • A family history of congenital or hereditary immunodeficiency
  • Chronic or active neurologic disease including seizure disorder
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination, or abnormal baseline laboratory screening tests.
  • Abnormal baseline EKG obtained at screening
  • Acute disease at the time of enrollment
  • Hepatomegaly, right upper quadrant abdominal pain or tenderness: noted by physical exam during the screening process.
  • Administration of immunoglobulins and/or any blood products within the three months preceding immunization during the study period
  • Use of kanamycin or related antibiotics
  • Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination
  • Inability to make follow-up visits
  • Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00870987
Other Study ID Numbers  ICMJE WRAIR 1550
HRPO #A-15350
NMRC.2009.0004
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party U.S. Army Medical Research and Materiel Command
Study Sponsor  ICMJE U.S. Army Medical Research and Materiel Command
Collaborators  ICMJE
  • United States Agency for International Development (USAID)
  • Walter Reed Army Institute of Research (WRAIR)
Investigators  ICMJE
Principal Investigator: Judith Epstein, MD US Military Vaccine Program, NMRC PI, Naval Officer
PRS Account U.S. Army Medical Research and Materiel Command
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP