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

Phase 2
Completed
Conditions
HIV Infections
Interventions
Biological: IMVAMUNE (MVA-BN)
Registration Number
NCT00316589
Lead Sponsor
Bavarian Nordic
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
581
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HIV-infected, vaccinia-experiencedIMVAMUNE (MVA-BN)Subjects with a history of previous smallpox vaccination, IMVAMUNE (MVA-BN)
HIV-infected, vaccinia-naiveIMVAMUNE (MVA-BN)Subjects without a history of previous smallpox vaccination, IMVAMUNE (MVA-BN)
Healthy subjectsIMVAMUNE (MVA-BN)Control group with and without a history of previous smallpox vaccination IMVAMUNE (MVA-BN)
Primary Outcome Measures
NameTimeMethod
Serious Adverse Eventswithin 32 weeks

Incidence, relationship and intensity of any Serious Adverse Event (SAE)

Secondary Outcome Measures
NameTimeMethod
Unsolicited Adverse Events: Incidencewithin 29 days after any vaccination

Incidence of any unsolicited adverse events

Unsolicited Adverse Events: Intensitywithin 29 days after any vaccination

Occurrence of unsolicited adverse events by Intensity

Unsolicited Adverse Events: Relationship to Vaccinationwithin 29 days after any vaccination

Occurrence of unsolicited adverse events by relationship to study vaccine

CD4+ T-cell Countswithin 32 weeks

Median CD4+ T-cell counts over time

CD8+ T-cell Countswithin 32 weeks

Median CD8+ T-cell counts over time

Viral Loadwithin 32 weeks

Viral load (HIV-1 RNA levels) over time

Related Grade >=3 Adverse Eventswithin 29 days after any vaccination

Incidence of any Grade 3 or higher adverse drug reaction (missing, unknown, not evaluable, possibly, probably, or definitely related) to the study vaccine

Solicited Local Adverse Eventswithin 8 days after any vaccination

Incidence and intensity of solicited local AEs (pain, erythema, swelling). Percentages based on subjects with at least one completed diary card.

Solicited General Adverse Eventswithin 8 days after any vaccination

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.

PRNT Seroconversion Ratewithin 32 weeks

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.

PRNT GMTwithin 32 weeks

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'.

ELISA Seroconversion Ratewithin 32 weeks

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.

ELISA GMTwithin 32 weeks

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'.

ELISPOT IFN-γ: Response Ratewithin 32 weeks

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.

ELISPOT IFN-γ: SFUwithin 32 weeks

Median number of interferon gamma (IFN-γ) secreting peripheral blood mononuclear cells (PBMC) in response to stimulation with MVA-BN detected by ELISPOT assay.

Trial Locations

Locations (36)

AltaMed Health Services

🇺🇸

Los Angeles, California, United States

The CORE Center

🇺🇸

Chicago, Illinois, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Clinical Trials Research Services

🇺🇸

Pittsburgh, Pennsylvania, United States

University of South Carolina

🇺🇸

Columbia, South Carolina, United States

Valley AIDS Council

🇺🇸

Harlingen, Texas, United States

Benchmark Clinical Research

🇺🇸

San Francisco, California, United States

Alabama Vaccine Research Clinic; University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Health for Life Clinic, PLLC

🇺🇸

Little Rock, Arkansas, United States

University of Iowa, Division of Infectious Diseases

🇺🇸

Iowa City, Iowa, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

The Kinder Medical Group

🇺🇸

Miami, Florida, United States

Consultive Medicine

🇺🇸

Daytona Beach, Florida, United States

CSI Clinical Trials, Inc.

🇺🇸

Fountain Valley, California, United States

Atlanta ID Group

🇺🇸

Atlanta, Georgia, United States

Northern California Research

🇺🇸

Carmichael, California, United States

Clinical Research of West Florida

🇺🇸

Clearwater, Florida, United States

Northpoint Medical, PA

🇺🇸

Fort Lauderdale, Florida, United States

Infectious Diseases of NW Florida

🇺🇸

Pensacola, Florida, United States

Palm Beach Center

🇺🇸

West Palm Beach, Florida, United States

Indiana University School of Medicine; Division of Infectious Disease

🇺🇸

Indianapolis, Indiana, United States

St. Louis University, Center for Vaccine Dev.

🇺🇸

Saint Louis, Missouri, United States

Northstar Medical Center

🇺🇸

Chicago, Illinois, United States

Diversified Medical Practices

🇺🇸

Houston, Texas, United States

Nemechek Health Renewal

🇺🇸

Kansas City, Missouri, United States

Vanderbilt University, AIDS Clinical Trials Center

🇺🇸

Nashville, Tennessee, United States

Universtity of Rochester School of Medicine

🇺🇸

Rochester, New York, United States

Nicholaos C. Bellos, MD PA

🇺🇸

Dallas, Texas, United States

Brown Medical School

🇺🇸

Providence, Rhode Island, United States

Maternal Infant Studies Center (CEMI)

🇵🇷

San Juan, Puerto Rico

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

University of Oklahoma

🇺🇸

Oklahoma City, Oklahoma, United States

Alta Bates Summit Medical Center, East Bay AIDS Center

🇺🇸

Oakland, California, United States

Providence Clinical Research

🇺🇸

Burbank, California, United States

Clinical Research P.R., Inc.

🇵🇷

San Juan, Puerto Rico

Immuniodeficiency Clinic, ECMC

🇺🇸

Buffalo, New York, United States

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