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Phase II Trial to Assess Safety and Immunogenicity of IMVAMUNE®

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01827371
First received: April 4, 2013
Last updated: September 25, 2014
Last verified: July 2014
  Purpose

Imvamune (licensed name of MVA being developed as a smallpox vaccine) has been tested in over 2,000 individuals and is on path for licensure. This study will be a Phase II to evaluate three different immunization schedules and two different modes of delivery. The study will look at condensed schedules. Study will randomize subjects to one of four arms.


Condition Intervention Phase
Smallpox
Biological: IMVAMUNE®
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II, Randomized, Open-Label Study to Evaluate the Safety and Immunogenicity of IMVAMUNE® Using Three Immunization Schedules and Two Modes of Delivery

Resource links provided by NLM:


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

Primary Outcome Measures:
  • For each subject, the peak Plaque reduction neutralization titer (PRNT) will be defined as the highest titer among all available measurements post second vaccination [ Time Frame: Day 1 after the first vaccination through Day 29 after the 2nd vaccination. ] [ Designated as safety issue: No ]
  • Occurrence of solicited local injection site reactions in subjects receiving vaccine via the Stratis™ compared to syringe and needle administration as collected on the memory aid and by in clinic assessment [ Time Frame: Day 1 after the 1st vaccination to Day 29 after the 2nd vaccination. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The occurrence of Serious Adverse Events (SAEs) associated with IMVAMUNE throughout the study (through last visit for each subject) for all four study arms [ Time Frame: Day 1 after the first vaccination through 180 days after the 2nd vaccination. ] [ Designated as safety issue: Yes ]
  • For each subject, the peak ELISA titer will be defined as the highest titer among all available measurements post second vaccination [ Time Frame: Day 1 after the first vaccination through Day 29 after the 2nd vaccination. ] [ Designated as safety issue: No ]

Estimated Enrollment: 440
Study Start Date: June 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm B
88 subjects receive IMVAMUNE® 1x10^8 TCID50/0.5 mL subcutaneously (SC) via syringe and needle on Days 1 and 15.
Biological: IMVAMUNE®
Subjects receive two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) via the SC route using either a syringe and needle or the Stratis™ system. Arm A receives doses via syringe and needle on days 1 and 29; Arm B receives doses via syringe and needle on days 1 and 15, Arm C receives doses via syringe and needle on days 1 and 22, Arm D receives doses via Stratis on days 1 and 29.
Experimental: Arm A
88 subjects receive IMVAMUNE® 1x10^8 TCID50/0.5 mL subcutaneously (SC) via syringe and needle on Days 1 and 29.
Biological: IMVAMUNE®
Subjects receive two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) via the SC route using either a syringe and needle or the Stratis™ system. Arm A receives doses via syringe and needle on days 1 and 29; Arm B receives doses via syringe and needle on days 1 and 15, Arm C receives doses via syringe and needle on days 1 and 22, Arm D receives doses via Stratis on days 1 and 29.
Experimental: Arm C
88 subjects receive IMVAMUNE® 1x10^8 TCID50/0.5 mL subcutaneously (SC) via syringe and needle on Days 1 and 22.
Biological: IMVAMUNE®
Subjects receive two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) via the SC route using either a syringe and needle or the Stratis™ system. Arm A receives doses via syringe and needle on days 1 and 29; Arm B receives doses via syringe and needle on days 1 and 15, Arm C receives doses via syringe and needle on days 1 and 22, Arm D receives doses via Stratis on days 1 and 29.
Experimental: Arm D
88 subjects receive IMVAMUNE® 1x10^8 TCID50/0.5 mL subcutaneously (SC) via Stratis™ on Days 1 and 29.
Biological: IMVAMUNE®
Subjects receive two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) via the SC route using either a syringe and needle or the Stratis™ system. Arm A receives doses via syringe and needle on days 1 and 29; Arm B receives doses via syringe and needle on days 1 and 15, Arm C receives doses via syringe and needle on days 1 and 22, Arm D receives doses via Stratis on days 1 and 29.

Detailed Description:

This is a Phase II, randomized, open-label immunogenicity and safety study of different immunization schedules and delivery systems (syringe and needle vs. the Stratis™) in healthy, vaccinia-naïve adults 18 years to 40 years of age, inclusive. Approximately 352 subjects will be enrolled and randomized to one of four study arms. Study Arm A (N=88) will receive a two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) via the SC route using a syringe and needle on Day 1 and 29. Study Arm B (N=88) will receive a two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) via the SC route using a syringe and needle on Day 1 and 15. Study Arm C (N=88) will receive a two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL) via the SC route using a syringe and needle on Day 1 and 22. Study Arm D (N=88) will receive a two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL) via the SC route using the Stratis™ on Day 1 and 29. Immunogenicity assessments will be performed using ELISA and PRNT. Safety assessments will be done via solicited injection site and systemic reactions. Unsolicited AEs will be collected until 28 days post last injection and SAEs for the duration of the subjects' study participation. Safety laboratory assessments will be performed at baseline and 14 days after each vaccination. Primary outcome measures: For each subject, the peak PRNT will be defined as the highest titer among all available measurements post second vaccination; Occurrence of solicited local injection site reactions in subjects receiving vaccine via the Stratis™ compared to syringe and needle administration as collected on the memory aid and by in clinic assessment. Parent protocol to sub-study 13-0027.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 18 to 40 years of age, inclusive.
  2. Read, signed, and dated informed consent document.
  3. Available for follow-up for the planned duration of the study (six months after last immunization).
  4. Acceptable medical history by screening evaluation and limited physical assessment.
  5. If the subject is female and of childbearing potential, negative serum or urine pregnancy test at screening and within 24 hours prior to vaccination.
  6. If the subject is female and of childbearing potential*, she agrees to practice abstinence** or use acceptable contraception*** through 56 days after the last vaccination in order to avoid pregnancy:

    * a woman is considered of childbearing potential unless post-menopausal (>/= 1 year without menses) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy)

    **No sexual intercourse with men (vaginal penetration by a penis, coitus)

    ***Acceptable contraception methods are restricted to effective devices (IUDs, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, condoms with spermicidal agents, monogamous relationship with a vasectomized partner who has been vasectomized for 6 months or more prior to study entry, or successful Essure placement with documented confirmation test at least 3 months after the procedure, and any other FDA-approved contraceptive method

  7. Negative test for HIV.
  8. Alanine Aminotransferase (ALT) <1.25 times the central lab upper limit of normal.
  9. Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
  10. Negative urine glucose and negative or trace urine protein by dipstick or urinalysis.
  11. Adequate renal function (defined as a serum creatinine not exceeding the central lab's upper limit of normal).
  12. Electrocardiogram (ECG) with no clinically significant abnormalities*

    * e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrhythmia, or two PVC's in a row, or ST elevation consistent with ischemia)

  13. Acceptable hematology parameters:

    • Hemoglobin (Hgb) equal or above the lower limit of central lab normal (sex-specific);
    • White Blood Cell (WBC) > 3,800 and < 10,900/mm^3;
    • Platelets >/=120,000/mm^3
  14. Body mass index >/=18.5-< 35.
  15. Be able to understand and comply with planned study procedures.

Exclusion Criteria:

  1. History of immunodeficiency.
  2. Typical vaccinia scar.
  3. Known or suspected history of smallpox vaccination including MVA alone or as a vector, as well as other investigational smallpox vaccines.
  4. Military service prior to 1991 or after January 2003.
  5. Known or suspected significant underlying illness including, but not limited to, clinically significant liver disease, diabetes mellitus, or moderate to severe kidney impairment.
  6. Malignancy (not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site) or history of skin cancer at the vaccination site.
  7. Active autoimmune disease. Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded.
  8. History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor*

    *Subjects with a not clinically relevant heart murmur, i.e., without any pathological ECG/arrhythmias or under treatment are not excluded.

  9. Systolic blood pressure >/= 150mmHg or diastolic blood pressure >/= 100mmHg.
  10. 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 (NCEP) risk assessment tool*

    *NOTE that this criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply:

    • have smoked a cigarette in the past month, and/or
    • have hypertension (defined as systolic blood pressure >140 mm Hg) or are on antihypertensive medication, and/or
    • have a family history of coronary heart disease in male first-degree relative (father or brother) <55 years of age or a female first-degree relative (mother or sister) <65 years of age

    URL for NCEP risk assessment tool: http://cvdrisk.nhlbi.nih.gov/calculator.asp (if a subject has an HDL of greater than 100mg/dl please enter 100 in the tool)

  11. High-dose corticosteroid use for greater than 2 weeks duration within three months prior to vaccination or current use of immunosuppressive medication:

    • >5 mg prednisone or equivalent is considered high dose and immunosuppressive
    • Corticosteroid nasal sprays for allergic rhinitis are permissible
    • Persons who are using a topical steroid for mild uncomplicated dermatitis such as poison ivy or contact dermatitis may be enrolled the day after their therapy is completed
    • Inhaled steroids for asthma are not permissible
    • Oral/parenteral corticosteroids given for non-chronic conditions not expected to recur are permissible if the length of therapy was </= 14 days with completion at least 30 days prior to enrollment.
  12. Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol.
  13. Any history of illegal injection drug use.
  14. Receipt or planned receipt of inactivated vaccine from 14 days prior to the first vaccination through 14 days post second vaccination.
  15. Receipt or planned receipt of any other live attenuated vaccine within 30 days prior to the first vaccination through 30 days post second vaccination.
  16. Use of any other experimental agent within 30 days prior to vaccination and for the duration of the subject's participation in the study.
  17. Receipt of blood products or immunoglobulin, including Rhogam, within six months prior to vaccination.
  18. Donation of a unit of blood within 56 days prior to vaccination or planned donation prior to 28-days following the last vaccination.
  19. Pregnant or breastfeeding women.
  20. Active exfoliative skin disorders/conditions, current varicella zoster virus infection, or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2×2 cm.
  21. Any condition that, in the opinion of the investigator, might interfere with assessing the study objectives.
  22. Known allergy to egg, aminoglycoside (including gentamicin) or chicken.
  23. Study personnel.
  24. Allergic reaction to any vaccine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01827371

Contacts
Contact: Lisa A Jackson (206) 287-2061 jackson.l@ghc.org

Locations
United States, Georgia
Emory Vaccine Center - The Hope Clinic Recruiting
Decatur, Georgia, United States, 30030-1705
United States, Iowa
University of Iowa - Vaccine Research & Education Unit Recruiting
Iowa City, Iowa, United States, 52242-2600
United States, Maryland
University of Maryland Medical System - General Clinical Research Center (GCRC) Recruiting
Baltimore, Maryland, United States, 21201-1544
United States, Missouri
Saint Louis University - Center for Vaccine Development Recruiting
Saint Louis, Missouri, United States, 63104-1015
United States, Texas
Baylor College of Medicine - Molecular Virology and Microbiology Recruiting
Houston, Texas, United States, 77030-3411
United States, Washington
Group Health Research Institute - Seattle Recruiting
Seattle, Washington, United States, 98101-1466
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01827371     History of Changes
Other Study ID Numbers: 11-0021, N01AI80004C
Study First Received: April 4, 2013
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on November 25, 2014