Ebola and Marburg Virus Vaccines

• Status: Completed
• Trial end date: 2010-06-21
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Criteria

• INCLUSION CRITERIA:

The following eligibility criteria apply to initial enrollment into the study:

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

Eligibility for the Optional 4th Study Injection:

Eligibility to receive a 4th injection requires the original consent (Appendix I) to be reviewed again with a study clinician, as well as the consent for the optional 4th injection (Appendix V) to be reviewed and signed. To be eligible the study subject must meet the following criteria:

• Has completed the 3-injection schedule for the Group in which he/she was enrolled.

• Has remained in follow-up through Study Week 32 without any serious adverse events.

• Meets the original study eligibility criteria for hemoglobin, platelets. PT. PTT. Creatinine and ALT within the 28 days prior to the 4th injection.

• Assessed as continuing to have a healthy vaccine study volunteer status by recent interim history and appropriate physical assessments.

• If a woman of reproductive potential, is willing to continue with a pregnancy prevention method (from among those meeting the original study eligibility) through 12 weeks after the injection and is confirmed as not pregnant on the day of the 4th injection prior to administration of the injection.

• Available for clinical follow-up through 12 weeks after the 4th injection.