cAd3-Marburg Vaccine in Healthy Adults
Condition: Marburg Virus Disease
MeSH terms: Virus Diseases; Marburg Virus Disease
Intervention: cAd3-Marburg vaccine
Intervention description: The recombinant chimpanzee adenovirus Type 3-vectored Marburg vaccine, VRC-MARADC087-00-VP (cAd3-Marburg) is composed of a cAd3 vector that expresses Marburg wild type glycoprotein (WT GP).
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Dose escalation
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Marburg virus; Marburg vaccine; cAd3-Marburg vaccine

Summary:

      RV 507 was a Phase I, open-label study to examine the safety, tolerability and immunogenicity
      of an investigational Marburg vaccine given by intramuscular (IM) injection to healthy
      adults. The study was a dose escalation of VRC-MARADC087-00-VP, a chimpanzee adenovirus
      serotype 3 (cAd3) vector vaccine, which encodes wild type (WT) glycoprotein (GP) from
      Marburgvirus.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 18 to 50 years old

          2. Available for clinical follow-up through Week 48 after enrollment

          3. Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process. Proof of identity includes a valid U.S.
             government-issued or state-issued photo identification (ID) such as a driver's
             license, military ID, or U.S. passport.

          4. Able and willing to provide a personal mobile phone number or home phone number at
             which the participant can be reliably contacted. Participants will be contacted
             primarily for study visit 2A (Appendix 1), as a reminder of an upcoming visit, and
             after missed visits for rescheduling purposes.

          5. Able and willing to complete the informed consent process and demonstrate
             understanding with a passing score (90% or greater) on the Assessment of Understanding
             (AOU) by the third attempt.

          6. In good general health without clinically significant medical history.

          7. Physical examination and laboratory results without clinically significant findings
             and a body mass index (BMI) ≤ 40 within the 56 days prior to enrollment.

          8. Laboratory Criteria within 56 days prior to enrollment:

               1. Hemoglobin ≥ 11.5 g/dL for women; ≥13.0 g/dL for men.

               2. White blood cells (WBC) = 3,300-12,000 cells/mm^3.

               3. Total lymphocyte count ≥ 800 cells/mm^3.

               4. Platelets = 125,000 - 400,000/mm^3.

               5. Alanine aminotransferase (ALT) ≤ 1.25 x upper limit of normal.

               6. Serum creatinine ≤ 1 x upper limit of normal.

               7. HIV-uninfected as evidenced by a negative FDA-approved HIV diagnostic blood test.

             Female-Specific Criteria:

          9. Negative β-HCG (human chorionic gonadotropin) pregnancy test; serum β-HCG at screening
             (or urine if screening is the same day as enrollment) and urine β-HCG at enrollment if
             woman is of reproductive potential.

         10. Agrees to use an effective means of birth control from at least 21 days prior to
             enrollment through 24 weeks after study vaccination if assessed to be of reproductive
             potential.

        Exclusion Criteria:

        Volunteer has received any of the following substances:

          1. Investigational Ebola or Marburg vaccine in a prior clinical trial or prior receipt of
             a cAd3 vectored investigational vaccine.

          2. Immunosuppressive medications within 2 weeks prior to enrollment.

          3. Blood products within 112 days (16 weeks) prior to enrollment.

          4. Investigational research agents within 28 days (4 weeks) prior to enrollment.

          5. Live attenuated vaccines within 28 days (4 weeks) prior to enrollment.

          6. Subunit or killed vaccines within 14 days (2 weeks) prior to enrollment.

          7. Current anti-tuberculosis prophylaxis or therapy.

             Female-specific criteria:

          8. Woman who is pregnant, breast-feeding or planning to become pregnant during the first
             24 weeks after study vaccine administration.

             Volunteer has a history of any of the following clinically significant conditions:

          9. Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives),
             respiratory difficulty, angioedema, or abdominal pain.

         10. Allergic reaction to excipients in the study vaccine including gentamycin, neomycin or
             streptomycin.

         11. Clinically significant autoimmune disease or immunodeficiency.

         12. Asthma that is not well controlled.

         13. Positive syphilis serology. False-positive results will also exclude a participant.

         14. Diabetes mellitus (type I or II).

         15. Thyroid disease that is not well controlled.

         16. A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic
             forms of angioedema.

         17. Idiopathic urticaria within the last 1 year.

         18. Hypertension that is not well controlled.

         19. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions) or significant bruising or bleeding
             difficulties with intramuscular (IM) injections or blood draws.

         20. A malignancy that is active, currently being treated, or not surgically cured.

         21. Seizure in the past 3 years or treatment for seizure disorder in the past 3 years.

         22. Asplenia or functional asplenia.

         23. Psychiatric condition that precludes compliance with the protocol; past or present
             psychoses; or within five years prior to enrollment, history of a 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 volunteer's ability to give informed consent.