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Ebola and Marburg Virus Vaccines
This study has been suspended.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00605514
  Purpose

This study will determine if experimental vaccines to prevent Ebola virus infection and Marburg virus infection are safe and what side effects, if any, they cause. Ebola virus infection may range from mild to severe, and may cause breathing problems, severe bleeding, kidney problems and shock that can lead to death. Marburg virus infection causes an illness similar to that caused by the Ebola virus. The vaccines used in this study contain genetic material produced in the laboratory that causes the body to make a small amount of either Ebola or Marburg virus proteins. No Ebola or Marburg virus is in the vaccines.

Normal healthy volunteers between 18 and 60 years of age may be eligible for this study.

Participants are assigned to receive injections of either the Marburg or the Ebola vaccine. The first group of participants will receive the Marburg vaccine and the second group will receive the Ebola vaccine. The injections are given at 4-week intervals (study weeks 0, 4 and 8). They are given into a muscle with a needleless system called the Biojector® (Registered Trademark) 2000.

Participants keep a diary at home (on paper or electronically) for 5 days, in which they record their temperature, symptoms and any reaction at the injection site. They call a study nurse the day after vaccination to report how they feel and return to the clinic for follow-up 2 weeks after each injection (weeks 2, 6 and 10). The visits include a check of vital signs, blood and urine tests, medical history and review of medications taken. Additional visits at weeks 12, 24 and 32 include a check of vital signs, medical history and blood tests.


Condition Intervention Phase
Ebola Vaccines
Marburg Virus Disease
Ebola Virus Disease
Marburgvirus
Ebolavirus
Drug: VRC-EBODNA023-00-VP
Drug: VRC-MARDNA025-00-VP
Phase I

MedlinePlus related topics: Fever Hemorrhagic Fevers
U.S. FDA Resources
Study Type: Interventional
Study Design: Prevention, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety Study
Official Title: VRC 206: A Phase I Study to Evaluate the Safety and Immunogenicity of an Ebola DNA Plasmid Vaccine, VRC-EBODNA023-00-VP, and a Marburg DNA Plasmid Vaccine, VRC-MARDNA025-00-VP, in Healthy Adults

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Safety (local and systemic reactogenicity, lab tests, AEs)

Secondary Outcome Measures:
  • Immunogenicity (cellular and humoral immune function assays)

Estimated Enrollment: 20
Study Start Date: January 2008
Intervention Details:
    Drug: VRC-EBODNA023-00-VP
    N/A
    Drug: VRC-MARDNA025-00-VP
    N/A
Detailed Description:

Study Design:

This is an open label Phase I study to evaluate safety, tolerability, and immunogenicity of two recombinant DNA vaccines: one against Marburg virus infections and one against Ebola virus infections. The hypothesis is that each vaccine will be safe for human administration and elicit a humoral and T cell mediated immune response. The primary objectives are to evaluate the safety and tolerability of the investigational vaccines in healthy adults. Secondary and exploratory objectives are related to the immunogenicity of each study vaccine.

Product Description:

VRC-MARDNA025-00-VP (Marburg DNA) is composed of one closed-circular DNA plasmid encoding for the glycoprotein (GP) from the Angola strain of Marburg. VRC-EBODNA023-00-VP (Ebola DNA WT) is composed of two closed-circular DNA plasmids, one encodes for GP from the Zaire strain and one encodes for GP from the Sudan-Gulu strain of Ebola. DNA vaccine vials will be supplied at 4 mg/mL. Each DNA vaccination will be 1 mL of vaccine administered intramuscularly (IM) into the deltoid muscle using the Biojector[R] 2000 Needle-Free Injection Management System (Biojector).

Subjects:

A total of 20 healthy adults, ages 18-60 years, will be enrolled into two groups of 10 subjects each. No more than one subject per group may be in the age range of 51-60 years.

Study Plan:

Subjects will be sequentially enrolled into two groups to receive three injections. Group 1 subjects will receive the Marburg DNA vaccine and Group 2 subjects will receive the Ebola DNA WT vaccine. The first 3 enrollments in each group will occur no faster than one per day. Before completing enrollment into each group, there will be a study pause with review by the Protocol Safety Review Team (PSRT) when there is at least 2 weeks of safety follow-up on the third subject's first injection. Before the initiation of Group 2, the FDA must have assessed administration of the Ebola DNA WT vaccine as safe to proceed. In addition, there will be a study pause with review by the PSRT when there is at least two weeks of safety follow-up on the last subject enrolled into Group 1. The protocol requires 9 clinic visits and 3 telephone follow-up contacts for each subject.

Study Duration: The study requires 32 weeks of clinical follow up for each participant.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

A participant must meet all of the following criteria:

  1. 18 to 60 years old
  2. Available for clinical follow-up through Week 32
  3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
  4. Complete an AoU prior to enrollment and verbalize understanding of all questions answered incorrectly
  5. Able and willing to complete the informed consent process
  6. Willing to donate blood for sample storage to be used for future research
  7. In good general health without clinically significant medical history
  8. Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) less than 40 within the 28 days prior to enrollment

    LABORATORY CRITERIA WITHIN 28 DAYS PRIOR TO ENROLLMENT:

  9. Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL for men
  10. White blood cells (WBC) = 3,300-12,000 cells/mm3
  11. Differential either within institutional normal range or accompanied by site physician approval
  12. Total lymphocyte count greater than or equal to 800 cells/mm3
  13. Platelets = 125,000 - 400,000/mm3
  14. Alanine aminotransferase (ALT) less than 1.25 upper limit of normal
  15. Serum creatinine less than or equal to 1 x upper limits of normal (less than or equal to1.3 mg/dL for females; less than or equal to 1.4 mg/dL for males)
  16. Normal urinalysis defined as negative glucose, negative or trace protein and no clinically significant blood in the urine
  17. Negative FDA-approved HIV blood test. [Note: Results of HIV ELISA will be documented, but a negative HIV polymerase chain reaction (PCR) test result will be sufficient for eligibility screening of subjects with positive HIV ELISA that is due to prior participation in an HIV vaccine study]
  18. Negative hepatitis B surface antigen (HBsAg)
  19. Negative anti-HCV and negative hepatitis C virus (HCV) PCR
  20. Partial thromboplastin time (PTT) within institutional normal range
  21. Prothrombin time (PT) less than or equal to upper limit of normal

    FEMALE-SPECIFIC CRITERIA:

  22. Negative Beta-HCG pregnancy test (urine or serum) for women presumed to be of reproductive potential
  23. A female participant must meet one of the following criteria:

    • No reproductive potential because of menopause [one year without menses] or because of a hysterectomy, bilateral oophorectomy, or tubal ligation,

OR

  • Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week 32 of the study,

OR

  • Participant agrees to consistently practice contraception at least 21 days prior to enrollment and through Week 32 of the study by one of the following methods:

    1. condoms, male or female, with or without a spermicide
    2. diaphragm or cervical cap with spermicide
    3. intrauterine device
    4. contraceptive pills or patch, Norplant, Depo-Provera or any other FDA-approved contraceptive method
    5. male partner has previously undergone a vasectomy

      EXCLUSION CRITERIA:

      A SUBJECT WILL BE EXCLUDED IF ONE OR MORE OF THE FOLLOWING CONDITIONS APPLY:

      Women:

      1. Breast-feeding or planning to become pregnant during the first 32 weeks after enrollment

        SUBJECT HAS RECEIVED ANY OF THE FOLLOWING SUBSTANCES:

      2. Investigational Ebola vaccine in a prior clinical trial
      3. Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or long-acting beta-agonists within the 12 weeks prior to enrollment. [With the exceptions that use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis, or short-acting beta-agonists in controlled asthmatics; or a short course (duration of 10 days or less, or a single injection) of corticosteroids for a non-chronic condition at least 2 weeks prior to enrollment in this study will not exclude study participation.]
      4. Blood products within 120 days prior to HIV screening
      5. Immunoglobulin within 60 days prior to HIV screening
      6. Live attenuated vaccines within 30 days prior to initial study vaccine administration
      7. Investigational research agents within 30 days prior to initial study vaccine administration
      8. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 14 days of study vaccine administration
      9. Current anti-tuberculosis prophylaxis or therapy

        SUBJECT HAS A HISTORY OF ANY OF THE FOLLOWING CLINICALLY SIGNIFICANT CONDITIONS:

      10. Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain
      11. Idiopathic urticaria within the past 2 years
      12. Autoimmune disease or immunodeficiency
      13. Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past 2 years or that requires the use of oral or parenteral corticosteroids
      14. Diabetes mellitus (type I or II), with the exception of gestational diabetes
      15. History of thyroidectomy or thyroid disease that required medication within the past 12 months
      16. A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema
      17. Hypertension that is not well controlled by medication or blood pressure that is more than 145/95 at enrollment
      18. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions), significant bruising or bleeding difficulties with IM injections or blood draws, or routine use of anticoagulant medications
      19. Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study
      20. Seizure disorder other than: 1) febrile seizures under the age of 2 years, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not requiring treatment within the last 3 years
      21. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
      22. Allergic reaction to aminoglycoside antibiotics
      23. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within 5 years prior to enrollment, a history of suicide plan or attempt
      24. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a subject's ability to give informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00605514

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

NIH Clinical Center Detailed Web Page  This link exits the ClinicalTrials.gov site

Publications:
Study ID Numbers: 080065, 08-I-0065
Study First Received: January 29, 2008
Last Updated: January 7, 2009
ClinicalTrials.gov Identifier: NCT00605514  
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Hemorrhagic Fever
Healthy
Immunity
T-Cells
Filovirus
Healthy Volunteer
HV

Study placed in the following topic categories:
Virus Diseases
Fever
Hemorrhagic Fevers, Viral
Ebola virus disease
Hemorrhagic Fever, Ebola
Marburg hemorrhagic fever
Hemorrhagic fever
Viral hemorrhagic fever
Healthy
Marburg Virus Disease

Additional relevant MeSH terms:
RNA Virus Infections
Filoviridae Infections
Mononegavirales Infections

ClinicalTrials.gov processed this record on January 14, 2009