Safety, Tolerability and Immune Response of IMVAMUNE (MVA-BN)Smallpox Vaccine in HIV Infected Patients

A Multicenter, Open-label Phase I/II Study to Evaluate Safety and Immunogenicity of MVA-BN® Smallpox Vaccine in HIV Infected Subjects (CD4 Counts >350 / µl) and Healthy Subjects With and Without Previous Smallpox Vaccination

The purpose of this study is to gather information on the safety and immunogenicity of an investigational smallpox vaccine in HIV infected populations.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: IMVAMUNE (MVA-BN)

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202-2859
      • Indiana University School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • University of Kentucky Medical Center
  • Missouri
    • St.Louis, Missouri, United States
      • Washington University School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-6073
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt AIDS Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male subjects between 18 and 49 years of age or female subjects between 18 and 55 years of age who provided informed consent.
• Women with negative pregnancy test.
• Women of childbearing potential must use an acceptable method of contraception.
• Cardiac enzymes within ULN.
• White blood cells ≥ 2500/mm3 and < 11,000/ mm3.
• Absolute neutrophil count ≥ 1000/mm3.
• Adequate renal function.
• Adequate hepatic function.
• Negative hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).
• Negative antibody test to hepatitis C virus (HCV).
• Negative urine glucose by dipstick or urinalysis.
• Normal 12-lead electrocardiogram.
• Availability for follow-up during the study.

Groups 1 and 3 (All vaccinia-naïve subjects) additionally:

• No history of known or suspected previous smallpox vaccination.
• No detectable vaccinia scar.
• No military service prior to 1989 or after January 2003.

Groups 2 and 4 (All previously vaccinated subjects) additionally:

• History of at least one previous smallpox vaccination
• Time since most current smallpox vaccination > 10 years.

Groups 1 and 2 (All HIV Infected subjects) additionally:

• Documented HIV-1 infection
• Plasma HIV-1 RNA level < 400 copies/mL at screening.
• CD4 cells ≥ 350/µL
• Haemoglobin ≥ 9.0 g/dL.
• Platelets ≥ 100,000/mm3.
• AST (SGOT), ALT (SGPT) and alkaline phosphatase ≤ 3 x ULN

Groups 3 and 4 (All Healthy subjects) additionally:

• Negative ELISA for HIV.
• Haemoglobin >11 g/dL.
• Platelets ≥ 140,000/mm3.
• AST (SGOT), ALT (SGPT) and alkaline phosphatase without clinically significant findings

Exclusion Criteria:

• Pregnant or breast-feeding women.
• Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
• History of any serious medical condition (other than HIV infection).
• History of or active autoimmune disease.
• Known or suspected impairment of immunologic function (other than HIV infection).
• History of malignancy.
• History or clinical manifestation of clinically significant and severe haematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
• Clinically significant mental disorder not adequately controlled by medical treatment.
• Any condition which might interfere with study objectives.
• History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor.
• History of an immediate family member with onset of ischemic heart disease before age 50.
• 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.
• History of chronic alcohol abuse and/or intravenous drug abuse.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Known previous allergic reaction to immunoglobulins.
• Known allergies to cidofovir or probenecid.
• History of anaphylaxis or severe allergic reaction.
• Acute disease (illness with or without a fever) at the time of enrollment.
• Temperature >100.4°F at the time of enrollment.
• Subjects undergoing treatment for tuberculosis infection or disease.
• Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior or after study vaccination.
• Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior or after study vaccination.
• Chronic administration of immuno-suppressant or immune-modifying drugs.
• Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.
• Administration or planned administration of immunoglobulins and/or any blood products.
• Use of any investigational or non-registered drug or vaccine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Occurrence, relationship and intensity of any serious and/or unexpected adverse reaction at any time during the study

Secondary Outcome Measures

Outcome Measure
Neutralisation assay specific seroconversion rates and geometric mean titres (at all blood sampling time points)
ELISA specific seroconversion rates and geometric mean titres (at all blood sampling time points)

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Richard N Greenberg, M.D., University Of Kentucky School of Medicine

Publications and helpful links

General Publications

• Greenberg RN, Overton ET, Haas DW, Frank I, Goldman M, von Krempelhuber A, Virgin G, Badeker N, Vollmar J, Chaplin P. Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia Ankara as a smallpox vaccine in HIV-infected subjects. J Infect Dis. 2013 Mar 1;207(5):749-58. doi: 10.1093/infdis/jis753. Epub 2012 Dec 7.

Study record dates

Study Major Dates

• Study Start: July 1, 2005

Study Registration Dates

• First Submitted: September 11, 2005
• First Submitted That Met QC Criteria: September 11, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Estimate): September 28, 2012
• Last Update Submitted That Met QC Criteria: September 27, 2012
• Last Verified: December 1, 2007

More Information

Terms related to this study

• Keywords: HIV
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Poxviridae Infections; Smallpox
• Other Study ID Numbers: POX-MVA-010; HHSN266200400072C (NIAID)