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

Study Overview
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Brief Summary
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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

Official Title
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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.

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: IMVAMUNE (MVA-BN)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, treatment experienced, treatment vaccinia naive