Safety and Immunogenicity of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in HIV Infected Patients

A Multicenter, Open-label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA-BN® (IMVAMUNE) Smallpox Vaccine in 18-55 Year Old Naive and Previously Vaccinated HIV Infected Subjects With CD4 Counts >200 - 750/µl.

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 581
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research P.R., Inc.
  • San Juan, Puerto Rico, 00936-5067
    • Maternal Infant Studies Center (CEMI)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-2050
      • Alabama Vaccine Research Clinic; University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • Health for Life Clinic, PLLC
  • California
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Carmichael, California, United States, 95608
      • Northern California Research
    • Fountain Valley, California, United States, 92708
      • CSI Clinical Trials, Inc.
    • Los Angeles, California, United States, 90022
      • AltaMed Health Services
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center, East Bay AIDS Center
    • San Francisco, California, United States, 94102
      • Benchmark Clinical Research
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida
    • Daytona Beach, Florida, United States, 32117
      • Consultive Medicine
    • Fort Lauderdale, Florida, United States, 33308
      • Northpoint Medical, PA
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Pensacola, Florida, United States, 32504
      • Infectious Diseases of NW Florida
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
    • Chicago, Illinois, United States, 60612
      • The CORE Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-2859
      • Indiana University School of Medicine; Division of Infectious Disease
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa, Division of Infectious Diseases
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Nemechek Health Renewal
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University, Center for Vaccine Dev.
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5130
      • University of Nebraska Medical Center
  • New York
    • Buffalo, New York, United States, 14260
      • Immuniodeficiency Clinic, ECMC
    • Rochester, New York, United States, 14642
      • Universtity of Rochester School of Medicine
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-6073
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • Clinical Trials Research Services
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Brown Medical School
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University, AIDS Clinical Trials Center
  • Texas
    • Dallas, Texas, United States, 75204
      • Nicholaos C. Bellos, MD PA
    • Harlingen, Texas, United States, 78550
      • Valley AIDS Council
    • Houston, Texas, United States, 77027
      • Diversified Medical Practices

Participation Criteria

Eligibility Criteria

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

Description

• Genders eligible for Study: Both
• Age: between 18 and 55 years
• Healthy volunteers are accepted

Inclusion Criteria:

• Subjects tested positive for HIV-1 infection (HIV-infected subjects).
• Subjects that are tested negative for HIV (Healthy subjects).
• Either on stable antiretroviral therapy or not on antiretroviral therapy.
• CD4 cells > = 200 - 750/µl.
• Subjects must be in good general health except for HIV infection.
• Women must not be pregnant and use an acceptable method of contraception.

Exclusion Criteria:

• Impairment of immunologic function (other than HIV infection).
• History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure.
• Uncontrolled serious infection.
• History of or active autoimmune disease.
• History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
• History of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before the age of 50 years.
• High risk of developing a myocardial infarction or coronary death.
• History of intravenous drug abuse (within the last 12 months).
• Known allergy to egg or aminoglycoside (gentamicin).
• History of anaphylaxis or severe allergic reaction.
• Subjects undergoing treatment for tuberculosis infection or disease.
• Chronic administration of systemic immuno-suppressants.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy subjects; Control group with and without a history of previous smallpox vaccination IMVAMUNE (MVA-BN)	Biological: IMVAMUNE (MVA-BN); 2 immunizations, four weeks apart: 1 x 10E8 TCID50, subcutaneous; Other Names: IMVANEX
Experimental: HIV-infected, vaccinia-naive; Subjects without a history of previous smallpox vaccination, IMVAMUNE (MVA-BN)	Biological: IMVAMUNE (MVA-BN); 2 immunizations, four weeks apart: 1 x 10E8 TCID50, subcutaneous; Other Names: IMVANEX
Experimental: HIV-infected, vaccinia-experienced; Subjects with a history of previous smallpox vaccination, IMVAMUNE (MVA-BN)	Biological: IMVAMUNE (MVA-BN); 2 immunizations, four weeks apart: 1 x 10E8 TCID50, subcutaneous; Other Names: IMVANEX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events	Incidence, relationship and intensity of any Serious Adverse Event (SAE)	within 32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ELISA GMT	Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'.	within 32 weeks
PRNT GMT	Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Titers below the detection limit are included with a value of '1'.	within 32 weeks
Related Grade >=3 Adverse Events	Incidence of any Grade 3 or higher adverse drug reaction (missing, unknown, not evaluable, possibly, probably, or definitely related) to the study vaccine	within 29 days after any vaccination
Solicited Local Adverse Events	Incidence and intensity of solicited local AEs (pain, erythema, swelling). Percentages based on subjects with at least one completed diary card.	within 8 days after any vaccination
Solicited General Adverse Events	Incidence of solicited general AEs (increased body temperature, headache, myalgia, chills, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card.	within 8 days after any vaccination
Unsolicited Adverse Events: Incidence	Incidence of any unsolicited adverse events	within 29 days after any vaccination
Unsolicited Adverse Events: Intensity	Occurrence of unsolicited adverse events by Intensity	within 29 days after any vaccination
Unsolicited Adverse Events: Relationship to Vaccination	Occurrence of unsolicited adverse events by relationship to study vaccine	within 29 days after any vaccination
CD4+ T-cell Counts	Median CD4+ T-cell counts over time	within 32 weeks
CD8+ T-cell Counts	Median CD8+ T-cell counts over time	within 32 weeks
Viral Load	Viral load (HIV-1 RNA levels) over time	within 32 weeks
PRNT Seroconversion Rate	Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.	within 32 weeks
ELISA Seroconversion Rate	Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.	within 32 weeks
ELISPOT IFN-γ: Response Rate	Response rate based on number of subjects with response in an interferon gamma (IFN-γ) ELISPOT assay. Response is defined as the appearance of a signal in subjects that had no signal at Baseline or a relative increase by a factor of ≥1.7 compared to Baseline in subjects that had a signal at Baseline. Percentages based on number of subjects with data available.	within 32 weeks
ELISPOT IFN-γ: SFU	Median number of interferon gamma (IFN-γ) secreting peripheral blood mononuclear cells (PBMC) in response to stimulation with MVA-BN detected by ELISPOT assay.	within 32 weeks

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Edgar Turner Overton, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Overton ET, Stapleton J, Frank I, Hassler S, Goepfert PA, Barker D, Wagner E, von Krempelhuber A, Virgin G, Meyer TP, Muller J, Badeker N, Grunert R, Young P, Rosch S, Maclennan J, Arndtz-Wiedemann N, Chaplin P. Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial. Open Forum Infect Dis. 2015 May 5;2(2):ofv040. doi: 10.1093/ofid/ofv040. eCollection 2015 Apr. Erratum In: Open Forum Infect Dis. 2016 Jan;3(1):ofv183.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: April 19, 2006
• First Submitted That Met QC Criteria: April 19, 2006
• First Posted (Estimate): April 21, 2006

Study Record Updates

• Last Update Posted (Actual): January 3, 2019
• Last Update Submitted That Met QC Criteria: December 7, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: HIV; treatment experienced; treatment vaccinia naive
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Poxviridae Infections; Smallpox
• Other Study ID Numbers: POX-MVA-011