Experimental Vaccine for Prevention of Ebola Virus Infection

Brief Title

Experimental Vaccine for Prevention of Ebola Virus Infection

Official Title

A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Recombinant Ebola Adenoviral Vector Vaccine, VRC-EBOADV018-00-VP, in Healthy Adults

Brief Summary

      This study will determine if an experimental vaccine to prevent Ebola virus infection is safe
      and what side effects, if any, it causes. 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. The vaccine used in this study contains man-made genetic material similar to
      one part of the Ebola virus, which is designed to stimulate an immune response to the virus.
      The vaccine itself cannot cause Ebola virus infection because it does not contain any Ebola
      virus.

      Participants are assigned to one of three groups as they enter into the study. Of the first
      16 people in the study, 12 receive the lowest study dose of vaccine and 4 receive placebo (an
      inactive substance). If this dose is safe, then of the next 16 people who enter the study, 12
      receive a higher dose of the vaccine, and the remaining 4 receive placebo. If this dose is
      safe, the final 12 people in the last group of 16 receive the highest study dose, and 4
      receive placebo. The vaccine is given as a single injection in the arm on the day of
      enrollment.

      Participants keep a diary for 5 days, recording 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 they return to the clinic approximately six times for follow-up evaluations. These
      visits may include a check of vital signs, physical examination, blood and urine tests, or
      other medical tests if needed.

      ...
    

Detailed Description

      Study Design:

      This is a Phase I, randomized, placebo-controlled, double-blinded study to examine safety,
      tolerability and immune response of a recombinant Ebola adenovirus serotype 5 vector
      (Ebola-rAd5) vaccine in healthy adults. The hypothesis is that this vaccine will be safe and
      elicit immune responses to Ebola. The primary objective is to evaluate the safety and
      tolerability of the investigational vaccine VRC-EBOADV018-00-VP in healthy subjects. The
      secondary objectives include immunogenicity evaluations and adenovirus serotype 5 antibody
      titers (Ad5 Ab) at Weeks 0, 4, and 24. Exploratory evaluations include immunogenicity
      evaluations at Weeks 2, 12, and 48.

      Product Description:

      VRC-EBOADV018-00-VP is a recombinant product composed of two replication-deficient
      recombinant adenovirus serotype 5 (rAd5) vectors encoding for glycoprotein (GP), one from the
      Zaire strain and one from the Sudan-Gulu strain of Ebola. The final formulation buffer will
      be used as the diluent and as the placebo control (Crucell placebo). Injections will be
      administered intramuscularly (IM) by needle and syringe.

      Subjects:

      Healthy adult subjects ages 18 to 50 years old.

      Study Plan:

      Forty-eight subjects will receive a 1 mL intramuscular (IM) deltoid injection, via needle and
      syringe, of the study agent or placebo in a deltoid muscle as shown in the schema. Dose
      escalation will occur about three weeks after the last injection in the preceding dose group
      following an interim safety data review by a Data and Safety Monitoring Board (DSMB),
      provided that there are no significant toxicities. No more than one subject per day will be
      enrolled for the first 6 enrollments into each dosage group and the sixth subject enrolled
      must have 5 days (Group 1) or 14 days (Group 2 and Group 3) of follow-up before proceeding
      with further enrollments into that group.

      Study Duration:

      Subjects will be evaluated at 7 or more clinical visits during the 48 weeks after the study
      injection.

      Study Endpoints:

      The primary endpoint is safety and tolerability of the vaccine administered at doses of 2 x
      10(9), 2 x 10(10) and 2 x 10(11) virus particles (VP) by IM injection. Secondary endpoints
      are immunogenicity as indicated by Ebola-specific antibody and cellular immune responses at
      Weeks 0, 4 and 24 and Ad5 antibody titer at Weeks 0, 4, and 24. Exploratory analyses of
      immunogenicity will also be conducted on stored samples collected at other timepoints
      including Weeks 2, 12 and 48.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Safety (local and systemic reactogenicity, lab tests, AE's).

Secondary Outcome

 Immunogenicity (cellular and humoral immune function assays).

Condition

Ebola Hemorrhagic Fever

Intervention

VRC-EBOADV018-00-VP


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

48

Start Date

September 5, 2006

Completion Date

May 5, 2009


Eligibility Criteria

        -  INCLUSION CRITERIA:

        A subject must meet all of the following criteria:

          1. 18 to 50 years old.

          2. Available for clinical follow-up through Week 48.

          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) equal to 3,300-12,000 cells/mm(3)

         11. Differential either within institutional normal range or accompanied by site physician
             approval

         12. Total lymphocyte count greater than or equal to 800 cells/mm(3)

         13. Platelets equal to 125,000 - 400,000/mm(3)

         14. Alanine aminotransferase (ALT) less than or equal to 1.25 upper limit of normal

         15. Serum creatinine less than or equal to 1 x upper limits of normal (less than or equal
             to 1.3 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, at low risk of HIV exposure as assessed by
             behavioral risk interview, and amenable to HIV risk reduction counseling. [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. a PTT within institutional normal range and PT less than or equal to upper limit of
             institutional normal range.

             Female-Specific Criteria:

         21. Negative beta-HCG pregnancy test (urine or serum) for women presumed to be of
             reproductive potential.

         22. 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 24 of the study, OR

               -  Participant agrees to consistently practice contraception at least 21 days prior
                  to enrollment and through Week 24 of the study by one of the following methods:

               -  condoms, male or female, with or without a spermicide

               -  diaphragm or cervical cap with spermicide

               -  intrauterine device

               -  contraceptive pills or patch, Norplant, Depo-Provera or any other FDA-approved
                  contraceptive method

               -  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 24 weeks after
             enrollment.

             Subject has received any of the following substances:

          2. Ebola vaccines or any recombinant adenoviral vector vaccine in a prior clinical trial.

          3. Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or
             long-acting beta-agonists within the past six months. [Note: that use of
             corticosteroid nasal spray for allergic rhinitis, topical corticosteroids for an acute
             uncomplicated dermatitis, or short-acting beta-agonists in controlled asthmatics are
             not excluded.]

          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 two 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 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 two, 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. 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.

         23. 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.

         24. A family history of pulmonary embolism associated with deep vein thrombosis without a
             known cause (such as hormonal contraceptive use or neoplasm) in a biologically related
             parent, sibling, child under the age of 60 years, or a family history of systemic
             lupus erythematosus in a biologically related parent, sibling, or child of any age.
      

Gender

All

Ages

18 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

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Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00374309

Organization ID

060237

Secondary IDs

06-I-0237


Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

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Verification Date

May 5, 2009