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Randomized, Open-label Phase II Trial to Assess the Safety and Immunogenicity of MVA-BN Smallpox Vaccine in Immunocompromised Subjects With HIV Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Bavarian Nordic
Sponsor:
Information provided by (Responsible Party):
Bavarian Nordic
ClinicalTrials.gov Identifier:
NCT02038881
First received: January 15, 2014
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

The main purpose of this clinical trial is to generate additional safety data in a highly immunocompromised population. HIV-infected persons are considered excellent candidates to represent the highly immunocompromised population for enrolment in this trial. Additionally, the immune system's response (protection against smallpox as measured by the amount of antibodies produced) following injections of MVA-BN® smallpox vaccine will be evaluated. All participants in this trial will be randomly and evenly assigned to one of three groups to receive two, three or four injections. Group 1 will receive the standard regime consisting of one dose at each vaccination time point, Group 2 will receive two doses at each vaccination time point and Group 3 will receive a booster vaccination 12 weeks after the first dose of the standard vaccination schedule with MVA-BN® smallpox vaccine. Participation in the trial is scheduled to last up to 48 weeks.


Condition Intervention Phase
Smallpox
Biological: MVA-BN® smallpox vaccine
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: Randomized, Open-label Phase II Trial to Assess the Safety and Immunogenicity of MVA-BN Smallpox Vaccine When Increasing the Number of Injections Compared to the Standard Regimen in Immunocompromised Subjects With HIV Infection

Resource links provided by NLM:


Further study details as provided by Bavarian Nordic:

Primary Outcome Measures:
  • To assess the safety of MVA-BN® smallpox vaccine when increasing the dose or number of injections compared to the standard 2-dose regimen [ Time Frame: entire trial (up to 48 weeks) ] [ Designated as safety issue: Yes ]
    Occurrence, relationship and intensity of any serious and / or unexpected Adverse Event at any time during the trial.


Secondary Outcome Measures:
  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: Visit 4 (week 6) ] [ Designated as safety issue: No ]
    Geometric mean titers (GMTs) after vaccination with MVA-BN® smallpox vaccine measured by Enzyme-linked Immunosorbent Assay (ELISA) and Plaque Reduction Neutralization Test (PRNT) at trial Visit 4 for Group 2 compared to Group 1 and Group 3 (combined).

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: Visit 4 (week 6) and Visits 7 (week 14) ] [ Designated as safety issue: No ]
    GMTs after vaccination with MVA-BN® smallpox vaccine measured by ELISA and PRNT at trial Visit 7 of Group 3 compared to Visit 4 of Group 1 and Group 2 (separately).

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: Visit 4 (week 6) Visit 7 (week 16) ] [ Designated as safety issue: No ]
    GMTs after vaccination with MVA-BN® smallpox vaccine measured by ELISA and PRNT at trial Visit 7 of Group 3 compared to Visit 4 of Group 1 and Group 2 (separately).

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: Visit 1 (week 0), Visit 2 (week 2) and Visit 4 (week 6) ] [ Designated as safety issue: No ]
    Seroconversion after vaccination with MVA-BN® smallpox vaccine measured by ELISA and PRNT at trial Visit 4 of Group 2 compared to Group 1 and 3 (combined).

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: Visit 4 (week 6) and Visit 7 (week 16) ] [ Designated as safety issue: No ]
    Seroconversion after vaccination with MVA-BN® smallpox vaccine measured by ELISA and PRNT at trial Visit 7 of Group 3 compared to Visit 4 of Group 1 and Group 2 (separately).

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: FU Visit (6 months post last vaccination) ] [ Designated as safety issue: No ]
    Seroconversion after vaccination with MVA-BN® smallpox vaccine measured by ELISA and PRNT at 6 months FU Visit of Group 3 compared to FU Visit of Group 1 and Group 2 (separately).

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: Visit 1 (week 1), Visit 3 (week 4), Visit 4 (week 6) and FU Visit (6 months) ] [ Designated as safety issue: No ]
    GMTs and seroconversion after vaccination with MVA-BN® smallpox vaccine measured by ELISA and PRNT at all other immunogenicity sampling points (Visit 1, 3, 4, FU) of Group 2 and 3 (separately) compared to Group 1.

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: Visit 6 (week ) and Visit 7 (week ) ] [ Designated as safety issue: No ]
    GMTs and seroconversion after vaccination with MVA-BN® smallpox vaccine measured by ELISA and PRNT at trial Visit 6 and 7 of Group 3.

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: throughout entire trial ] [ Designated as safety issue: Yes ]
    Occurrence, relationship to the trial vaccine and intensity of any Adverse Event of Special Interest (AESI).

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: 28 days after each vaccination ] [ Designated as safety issue: Yes ]
    Occurrence of any Grade 3 or 4 Adverse Events (AEs) probably, possibly or definitely related to the trial vaccine within 28 days after each vaccination.

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: 28 days after each vaccination ] [ Designated as safety issue: Yes ]
    Occurrence, relationship to the trial vaccine and intensity of unsolicited non-serious AEs within 28 days after each vaccination.

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: 7 days following each vaccination ] [ Designated as safety issue: Yes ]
    Occurrence, intensity and duration of solicited local AEs (redness, swelling, induration, pruritus and pain) during the 8-day period (day of vaccination and the following 7 days) after each vaccination.

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: 7 days following each vaccination ] [ Designated as safety issue: Yes ]
    Occurrence, relationship to the trial vaccine, intensity and duration of solicited general AEs (pyrexia, headache, myalgia, nausea, fatigue and chills) during the 8-day period (day of vaccination and the following 7 days) after each vaccination.

  • To compare the immunogenicity and safety of three different vaccination strategies of MVA-BN® smallpox vaccine [ Time Frame: 2 weeks after each vaccination ] [ Designated as safety issue: Yes ]
    Change in CD4 T cell counts in Human Immunodeficiency Virus (HIV)-infected subjects 2 weeks after each vaccination.


Estimated Enrollment: 90
Study Start Date: April 2014
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 (standard regimen)
One injection at Day 0 and Day 28 with 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10 to the 8 Tissue Culture Infectious Dose 50% (TCID50) per ml
Biological: MVA-BN® smallpox vaccine
MVA-BN® smallpox vaccine
Experimental: Group 2 (double dose regimen)
Two injections at Day 0 and two injections at Day 28 with 0.5 ml MVA-BN® smallpox vaccine each containing at least 1 x 10 to the 8 TCID50 per ml
Biological: MVA-BN® smallpox vaccine
MVA-BN® smallpox vaccine
Experimental: Group 3 (booster regimen)
One injection at Day 0 and Day 28 with 0.5 ml MVA-BN® smallpox vaccine containing at least 1 x 10 to the 8 TCID50 per ml (standard regimen) and one booster injection at week 12
Biological: MVA-BN® smallpox vaccine
MVA-BN® smallpox vaccine

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1. Male and female subjects aged between 18-45 years, vaccinia-naïve. 2. HIV-1 infection documented by ELISA and confirmed by Western blot at any time prior to study entry. HIV-1 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), HIV-1 culture, HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA), or a second antibody test other than ELISA is acceptable as an alternative test at any time prior to study entry.

3. On stable antiretroviral therapy (ART) i.e. Combination ART for at least 6 months. Subject must be on the same ART regimen for at least 12 weeks with no change prior to enrollment in this clinical trial.

4. Screening HIV-1 RNA < 200 copies/ml by US Food and Drug Administration (FDA) approved PCR assay within 45 days prior to study entry.

5. Current CD4 counts ≥ 100 cells/µl ≤ 500 cells/µl. 6. Documented nadir CD4 count < 200 cells/µl at any time prior to enrollment. 7. Hemoglobin ≥ 9.0 g/dl for female subjects, ≥ 10.0 g/dl or male subjects. 8. Platelets ≥ 100,000/mm3. 9. Ability and willingness of subject to provide written informed consent. 10. Body Mass Index (BMI) ≥ 18.5 and < 35 kg/m2. 11. Women of childbearing potential (WOCBP) must have used an acceptable method of contraception for 30 days prior to the first vaccination, must agree to use an acceptable method of contraception during the trial, and must avoid becoming pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal (defined as ≥ 12 months without a menstrual period) or surgically sterilized. Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products).

12. WOCBP must have a negative serum pregnancy test at screening (SCR) and a negative urine pregnancy test within 24 hours prior to each vaccination.

13. Absolute neutrophil count cells ≥ 750/mm3. 14. Adequate renal function defined as a calculated Creatinine Clearance (CrCl) > 60 ml/min as estimated by the Cockcroft-Gault equation.

  1. For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl x 72) = CrCl (ml/min)
  2. For women: multiply the result by 0.85 = CrCl (ml/min).Adequate hepatic function defined as: Total bilirubin ≤ 2 x upper limit normal (ULN) in the absence of other evidence of significant liver disease

    15. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 x ULN.

    16. Troponin I < 2 x ULN at entry in the clinical trial. 17. Electrocardiogram (ECG) without clinically significant findings (e.g. any kind 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, two premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia).

    Exclusion Criteria:1. Pregnant or breast-feeding women. 2. Typical vaccinia scar. 3. Known or suspected history of smallpox vaccination. 4. History of vaccination with any poxvirus-based vaccine. 5. Uncontrolled serious infection, i.e. not responding to antimicrobial therapy.

    6. History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject or would limit the subject's ability to complete the trial including uncontrolled diabetes as according to the 'Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events' Version 1.0, December 2004, Clarification August 2009.

    7. History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.

    8. Known or suspected impairment of immunologic function except those defined in the inclusion criteria, including, but not limited to clinically significant liver disease, diabetes mellitus type I and moderate to severe kidney impairment.

    9. History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer must not be vaccinated at the previous tumor site.

    10. History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders (except HIV infection, chronic or active Hepatitis-B-Virus or Hepatitis-C-Virus infection).

    11. Clinically significant psychiatric disorder not adequately controlled by medical treatment.

    12. History of coronary heart disease, myocardial infarction, angina pectoris, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor.

    13. Known history of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years.

    14. 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 (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof). NOTE: This criterion applies only to subjects 20 years of age and older.

    15. Current alcohol abuse (40 g/day for at least 6 month) and/or intravenous and/or intranasal drug abuse (within the past 6 months).

    16. Known allergy to MVA-BN® vaccine or any of its constituents, e.g. tris (hydroxymethyl)-amino methane, including known allergy to egg or aminoglycosides.

    17. History of anaphylaxis or severe allergic reaction to any vaccine. 18. Acute disease (illness with or without a fever) at the time of enrollment. 19. Body temperature ≥ 100.4°F (≥ 38.0°C) at the time of enrollment. 20. Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior to or after trial vaccination.

    21. Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior to or after trial vaccination.

    22. Use of immunosuppressant or immunomodulatory agents including systemic glucocorticoids (excluding nasal or inhaled steroids), tacrolimus, sirolimus, rapamycin, mycophenolate, cyclosporine, TNF-alpha blockers or antagonists, azathioprine, interferon, growth factors, or intravenous immunoglobulin in the 60 days prior to enrollment in this clinical trial.

    23. Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.

    24. Administration or planned administration of immunoglobulins and/or any blood products during a period starting from three months prior to administration of the vaccine and ending at last physical trial visit.

    25. Use of any investigational or non-registered drug or vaccine other than the trial vaccine within 30 days preceding the first dose of the trial vaccine, or planned administration of such a drug during the trial period.

    26. Trial personnel.

  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: NCT02038881

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Aeryn Peck    205-934-6775    temple88@uab.edu   
Principal Investigator: Edgar T Overton, MD         
Sub-Investigator: Paul Goepfert, MD         
Sub-Investigator: Catrena Johnson, RN         
Sub-Investigator: Leslie Christian, RN         
Sub-Investigator: Tarana Billups, Pharm D         
Sub-Investigator: Sonya Heath, MD         
Sub-Investigator: Pamela Cunningham, RN         
Sub-Investigator: Deon Powell, Pharm D         
Sub-Investigator: Kristie Heath, Pharm D         
Sub-Investigator: Ricardo Franco, MD         
Sub-Investigator: Aeryn Peck, RN         
Sub-Investigator: Amy Player, Pharm D         
United States, Arkansas
Health for Life Clinic Little Rock Recruiting
Little Rock, Arkansas, United States, 72207
Contact: Doris Walker       dwalker@hflclinic.com   
Principal Investigator: Thomas T Jefferson, MD         
Sub-Investigator: Tammy Miller, RNP, BSN         
United States, Florida
Infectious Disease Associats of NW Florida Center for Prevention and Treatment of Infections Infectious Diseases Associates of NW FL Recruiting
Pensacola, Florida, United States, 32504
Contact: Ann Brown    850-476-3131    abrown@infectioncenter.com   
Principal Investigator: Barbara H Wade, MD FACP         
Sub-Investigator: William M Vaughan, MHS PA-C PhD         
Sub-Investigator: Ethan W Rhone, PA-C         
Sub-Investigator: Jennifer F Buck, PA-C         
United States, Illinois
University of Illinois - Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Justin A Franz    312-413-8412    jfranz@uic.edu   
Principal Investigator: Richard M Novak, MD         
Sub-Investigator: Stockton M Mayer, DO         
Sub-Investigator: Triniece Pearson, MBA BSN RN         
Sub-Investigator: Justin A Franz         
United States, Iowa
University of Iowa Departments of Internal Medicine and Microbiology University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Wendy Sauter    319-353-7919    wendy-sauter@uiowa.edu   
Principal Investigator: Jack T Stapleton, MD         
Sub-Investigator: Patricia L Winokur, MD         
Sub-Investigator: Dilek Ince, MD         
Sub-Investigator: Kathryn L Flanders, MS MSN ARNP         
Sub-Investigator: Wendy Sauter, RN BSN BS         
Sub-Investigator: Jeffery Meier, MD         
Sub-Investigator: Deborah Pearson, RN         
Sub-Investigator: Rina Chaudhary, MA EDS         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Teresa Spitz    314-747-1915    tspitz@dom.wustl.edu   
Principal Investigator: Steven J Lawrence, MD MSc         
Sub-Investigator: Rachel M Presti, MD PhD         
Sub-Investigator: David B Clifford, MD         
Sub-Investigator: Michael K Klebert, RN PhD         
United States, Pennsylvania
University of Pennsylvania Clinical Trials Unit Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joseph Quinn    215-349-8091    joseph.quinn@uphs.upenn.edu   
Principal Investigator: Ian Frank, MD         
Sub-Investigator: Pablo Tebas, MD         
Sub-Investigator: Susan L Hansen-Flaschen, MSN RN CRNP         
Sub-Investigator: Eileen Hollen, CRNP         
Sponsors and Collaborators
Bavarian Nordic
Investigators
Principal Investigator: Edgar T Overton, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: Bavarian Nordic
ClinicalTrials.gov Identifier: NCT02038881     History of Changes
Other Study ID Numbers: POX-MVA-037
Study First Received: January 15, 2014
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Smallpox
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Poxviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on September 14, 2014