Combination Study With MVA BN and Dryvax

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00082446
First received: May 10, 2004
Last updated: May 10, 2013
Last verified: September 2008
  Purpose

The overall goals of this study are to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naive adults and to determine the optimum dose of MVA-BN to induce immune responses and attenuate Dryvax take reactions. Participants will include 90 healthy volunteers, ages 18-32 years. Participants will be randomly assigned to 1 of 6 study groups (groups A-F). Participants will be involved in study related procedures for up to 2 years. During this time, volunteers will return periodically for blood draws to check immune responses.


Condition Intervention Phase
Smallpox
Drug: Placebo (scarification)
Biological: Dryvax
Drug: Placebo (SC)
Biological: MVA-BN (SubQ)
Biological: MVA-BN (IM)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of MVA-BN in a Dose Response Regimen Followed by Administration of Dryvax in Healthy Adult Volunteers

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Adverse Events and side effects to the vaccines. [ Time Frame: Reactogenicity will be evaluated for a 2-week period post-vaccination at each time point and for the duration of study. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunogenicity testing of antibody and cellular responses to the vaccines. [ Time Frame: Visit days 0, 14, 28, 42, 56, 112, 140, 182, 365, and 730. ] [ Designated as safety issue: No ]

Enrollment: 91
Study Start Date: May 2004
Study Completion Date: August 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: D
Subject will receive a SC dose of placebo on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification.
Biological: Dryvax
Dryvax® is a live vaccinia virus, freeze dried, calf lymph type, smallpox vaccine. Each reconstituted vial contains 0.25 mL of vaccine with a concentration of approximately 1X 10^8 live vaccinia virus per mL. The Dryvax® will be administered by the standard route of scarification using a bifurcated needle.
Drug: Placebo (SC)
Sterile saline placebo for injection.
Experimental: F
Subject will receive an IM dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification.
Biological: Dryvax
Dryvax® is a live vaccinia virus, freeze dried, calf lymph type, smallpox vaccine. Each reconstituted vial contains 0.25 mL of vaccine with a concentration of approximately 1X 10^8 live vaccinia virus per mL. The Dryvax® will be administered by the standard route of scarification using a bifurcated needle.
Biological: MVA-BN (IM)
MVA-BN is a highly attenuated live vaccinia virus. The product is freeze-dried and must be reconstituted with sterile water. The reconstituted vaccine contains approximately 2x10^8 tissue cultured infectious dose 50 per mL. A dose of 1x10^8 will be administered intramuscularly.
Experimental: E
Subject will receive an SC dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of placebo by scarification.
Drug: Placebo (scarification)
Sterile saline placebo for injection.
Biological: MVA-BN (SubQ)
MVA-BN is a highly attenuated live vaccinia virus. The product is freeze-dried and must be reconstituted with sterile water. The reconstituted vaccine contains approximately 2x10^8 tissue cultured infectious dose 50 per mL. The following doses will be administered subcutaneously: 2x10^7, 5x10^7, 1x10^8.
Experimental: C
Subject will receive a SC dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification.
Biological: Dryvax
Dryvax® is a live vaccinia virus, freeze dried, calf lymph type, smallpox vaccine. Each reconstituted vial contains 0.25 mL of vaccine with a concentration of approximately 1X 10^8 live vaccinia virus per mL. The Dryvax® will be administered by the standard route of scarification using a bifurcated needle.
Biological: MVA-BN (SubQ)
MVA-BN is a highly attenuated live vaccinia virus. The product is freeze-dried and must be reconstituted with sterile water. The reconstituted vaccine contains approximately 2x10^8 tissue cultured infectious dose 50 per mL. The following doses will be administered subcutaneously: 2x10^7, 5x10^7, 1x10^8.
Experimental: B
Subjects will receive a SC dose of MVA 5x10^7 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification.
Biological: Dryvax
Dryvax® is a live vaccinia virus, freeze dried, calf lymph type, smallpox vaccine. Each reconstituted vial contains 0.25 mL of vaccine with a concentration of approximately 1X 10^8 live vaccinia virus per mL. The Dryvax® will be administered by the standard route of scarification using a bifurcated needle.
Biological: MVA-BN (SubQ)
MVA-BN is a highly attenuated live vaccinia virus. The product is freeze-dried and must be reconstituted with sterile water. The reconstituted vaccine contains approximately 2x10^8 tissue cultured infectious dose 50 per mL. The following doses will be administered subcutaneously: 2x10^7, 5x10^7, 1x10^8.
Experimental: A
Subjects will receive a SC dose of MVA 2x10^7 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification.
Biological: Dryvax
Dryvax® is a live vaccinia virus, freeze dried, calf lymph type, smallpox vaccine. Each reconstituted vial contains 0.25 mL of vaccine with a concentration of approximately 1X 10^8 live vaccinia virus per mL. The Dryvax® will be administered by the standard route of scarification using a bifurcated needle.
Biological: MVA-BN (SubQ)
MVA-BN is a highly attenuated live vaccinia virus. The product is freeze-dried and must be reconstituted with sterile water. The reconstituted vaccine contains approximately 2x10^8 tissue cultured infectious dose 50 per mL. The following doses will be administered subcutaneously: 2x10^7, 5x10^7, 1x10^8.

Detailed Description:

The primary goal of this phase I trial is to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naïve adults. The secondary goals of this vaccine trial are: to determine the optimum dose of MVA-BN, given twice, to induce an immune response and attenuate Dryvax® take reactions; and to compare the ability of 2 routes of administration of MVA-BN, subcutaneous and intramuscular, to induce an immune response at the highest tested dose. A total of 90 healthy adult volunteers ages 18-32 will participate in this study. The volunteers will be randomly assigned to 1 of 6 groups to be immunized with: MVA-BN (subcutaneously) at 1 of 3 dose levels and Dryvax® (per scarification); placebo (subcutaneously) and Dryvax® (per scarification); MVA-BN (subcutaneously) at the highest dose level and placebo scarification; or MVA-BN (intramuscularly) at the highest dose level and Dryvax® (per scarification). The study will last about 30 months. Each volunteer's participation will last 6 months for all treatment groups. Subjects randomized to treatment groups D and E will have follow-up for 2 years. During this time, volunteers will return periodically for blood draws to check immune responses. Subjects will require visits for dressing changes as needed post-Dryvax vaccination. Variables to be investigated include: adverse events and side effects to the vaccines, and immunogenicity testing including antibody and cellular responses to the vaccines.

  Eligibility

Ages Eligible for Study:   18 Years to 32 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Ages 18-32.
  • Never received smallpox vaccination.
  • Read, signed and dated informed consent document.
  • Availability for follow-up for the planned duration of the study two years after first immunization.
  • Acceptable medical history by screening evaluation and limited physical examination.
  • For women, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to vaccination.
  • If the volunteer is female and of child bearing potential, she agrees to use acceptable contraception, and not become pregnant for at least 56 days after the last vaccination. A woman is considered of child bearing potential unless post-menopausal or surgically sterilized. [Acceptable contraception methods are restricted to effective intrauterine devices (IUDs) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination.] Women who are not sexually active must agree to use one of the acceptable contraception methods if they are of childbearing potential.
  • Negative ELISA for HIV.
  • ALT<1.25 times institutional upper limit of normal.
  • Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
  • Negative urine glucose by dipstick or urinalysis.
  • Adequate renal function defined as a serum creatinine less than or equal to 1.4mg/dL for males and less than or equal to 1.2mg/dL for females; urine protein < 30 mg/dL or none or trace proteinuria (by urinalysis or dipstick); and a calculated creatine clearance greater than or equal to 80 mL/min. based on the following formulas:
  • Males [(140-age in years) X weight in kg]/(72 X serum creatinine)
  • Females 0.85X[(140-age in years) X weight in kg]/(72 X serum creatinine)
  • ECG without clinical significance (e.g., all kinds of atrioventricular or intraventricular conditions or blocks such as complete left or right bundle branch block, AV-node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, or 2 premature ventricular contractions (PVC) in a row, or ST elevation consistent with ischemia)
  • CBC: Hemoglobin >11g/dl; White blood cells greater than 2,500 and less than 11,000/cubic mm; Platelets greater than or equal to 140,000/cubic mm.

Exclusion Criteria:

  • History of immunodeficiency.
  • Typical vaccinia scar.
  • Known or suspected history of smallpox vaccination.
  • Military service prior to 1989 or after January 2003.
  • Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
  • Malignancy, including squamous cell skin cancer or basal cell skin cancer at vaccination site or history of skin cancer at the vaccination site.
  • Active autoimmune disease. Persons with vitiligo or thyroid disease on thyroid replacement are not excluded.
  • History of keloid formation.
  • History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor.
  • History of an immediate family member (father, mother, brother or sister) who has had onset of ischemic heart disease before age 50 years.
  • Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's Risk Assessment Tool for Estimating Your 10-Year Risk of Having a Heart Attack, located at the following URL: http://hin.nhlbi.nih.gov/atpiii/calculator.asp. NOTE: This criterion applies only to volunteers 20 years of age and older.
  • Abnormal troponin I.
  • Use of immunosuppressive medication. Corticosteroid nasal sprays are permissible. Persons who have used topical steroid can be enrolled after their therapy is completed.
  • Medical or psychiatric condition or occupational responsibilities that preclude volunteer compliance with the protocol.
  • Any history of "illegal" injection drug use.
  • Receipt of inactivated vaccine 14 days prior to vaccination.
  • Receipt of live attenuated vaccines within 30 days of vaccination.
  • Use of experimental agents within 30 days prior to vaccination.
  • Receipt of blood products or immunoglobulin in the 6 months prior to vaccination.
  • Acute febrile illness (greater than or equal to 100.5 degrees F) on the day of vaccination.
  • Pregnant or lactating women.
  • Eczema of any degree or history of eczema.
  • People with atopic dermatitis, Varicella zoster, chronic exfoliative skin disorders/conditions or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2x2 cm.
  • Household contacts/sexual contacts with, or occupational exposure to (other than minimal contact), any of the following: Pregnant women; Children <12 months of age; People with or history of eczema; People with atopic dermatitis, Varicella zoster, chronic exfoliative skin disorders/conditions or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2x2 cm; People with immunodeficiency disease or use of immunosuppressive medications.
  • Any condition that, in the opinion of the investigator, might interfere with study objectives.
  • Known allergies to or any component of MVA or MVA-BN vaccine (e.g., tris(hydroxymethl)-amino methane, sodium chloride, sucrose, dextran, L-Glutamic acid monopotassium, chicken embryo fibroblast proteins, gentamycin).
  • Known allergy to egg or aminoglycoside.
  • Known allergies to any component of the Dryvax® vaccine (e.g. polymyxin B sulfate, dihydrostreptomycin sulfate, chlorotetracycline hydrochloride, neomycin sulfate).
  • Known allergies to any known component of the Dryvax® diluent (i.e. glycerin and phenol).
  • Known allergies to any known components of vaccinia immunoglobulin (VIG), i.e. thimerosal or previous allergic reaction to immunoglobulins.
  • Known allergies to cidofovir or probenecid.
  • Study personnel.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00082446

Locations
United States, Missouri
Saint Louis University
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00082446     History of Changes
Other Study ID Numbers: 02-017, POX-MVA-002
Study First Received: May 10, 2004
Last Updated: May 10, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Smallpox, vaccine

Additional relevant MeSH terms:
Smallpox
Poxviridae Infections
DNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on April 15, 2014