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

HIV Infections Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00316589
• Other study ID #: POX-MVA-011
• Status: Completed
• Phase: Phase 2
• Start date: June 2006
• Est. completion date: October 2009

Study information

• Verified date: December 2018
• Source: Bavarian Nordic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 581
• Est. completion date: October 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

• 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.

Related Conditions & MeSH terms

• HIV Infections
• Smallpox

Intervention

Biological:
• IMVAMUNE (MVA-BN)
2 immunizations, four weeks apart: 1 x 10E8 TCID50, subcutaneous

Locations

Country	Name	City	State
Puerto Rico	Clinical Research P.R., Inc.	San Juan
Puerto Rico	Maternal Infant Studies Center (CEMI)	San Juan
United States	Atlanta ID Group	Atlanta	Georgia
United States	Alabama Vaccine Research Clinic; University of Alabama at Birmingham	Birmingham	Alabama
United States	Immuniodeficiency Clinic, ECMC	Buffalo	New York
United States	Providence Clinical Research	Burbank	California
United States	Northern California Research	Carmichael	California
United States	Northstar Medical Center	Chicago	Illinois
United States	The CORE Center	Chicago	Illinois
United States	Clinical Research of West Florida	Clearwater	Florida
United States	University of South Carolina	Columbia	South Carolina
United States	Nicholaos C. Bellos, MD PA	Dallas	Texas
United States	Consultive Medicine	Daytona Beach	Florida
United States	Northpoint Medical, PA	Fort Lauderdale	Florida
United States	CSI Clinical Trials, Inc.	Fountain Valley	California
United States	Valley AIDS Council	Harlingen	Texas
United States	Diversified Medical Practices	Houston	Texas
United States	Indiana University School of Medicine; Division of Infectious Disease	Indianapolis	Indiana
United States	University of Iowa, Division of Infectious Diseases	Iowa City	Iowa
United States	Nemechek Health Renewal	Kansas City	Missouri
United States	Health for Life Clinic, PLLC	Little Rock	Arkansas
United States	AltaMed Health Services	Los Angeles	California
United States	The Kinder Medical Group	Miami	Florida
United States	Vanderbilt University, AIDS Clinical Trials Center	Nashville	Tennessee
United States	Alta Bates Summit Medical Center, East Bay AIDS Center	Oakland	California
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Infectious Diseases of NW Florida	Pensacola	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Clinical Trials Research Services	Pittsburgh	Pennsylvania
United States	Brown Medical School	Providence	Rhode Island
United States	Universtity of Rochester School of Medicine	Rochester	New York
United States	St. Louis University, Center for Vaccine Dev.	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Benchmark Clinical Research	San Francisco	California
United States	Palm Beach Center	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Bavarian Nordic	National Institutes of Health (NIH)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

Overton ET, Stapleton J, Frank I, Hassler S, Goepfert PA, Barker D, Wagner E, von Krempelhuber A, Virgin G, Meyer TP, Müller J, Bädeker N, Grünert R, Young P, Rösch S, Maclennan J, Arndtz-Wiedemann N, Chaplin P. Safety and Immunogenicity of Modified Vacci — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serious Adverse Events	Incidence, relationship and intensity of any Serious Adverse Event (SAE)	within 32 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Unsolicited Adverse Events: Incidence	Incidence of any unsolicited adverse events	within 29 days after any vaccination
Secondary	Unsolicited Adverse Events: Intensity	Occurrence of unsolicited adverse events by Intensity	within 29 days after any vaccination
Secondary	Unsolicited Adverse Events: Relationship to Vaccination	Occurrence of unsolicited adverse events by relationship to study vaccine	within 29 days after any vaccination
Secondary	CD4+ T-cell Counts	Median CD4+ T-cell counts over time	within 32 weeks
Secondary	CD8+ T-cell Counts	Median CD8+ T-cell counts over time	within 32 weeks
Secondary	Viral Load	Viral load (HIV-1 RNA levels) over time	within 32 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	ELISPOT IFN-?: Response Rate	Response rate based on number of subjects with response in an interferon gamma (IFN-?) 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
Secondary	ELISPOT IFN-?: SFU	Median number of interferon gamma (IFN-?) secreting peripheral blood mononuclear cells (PBMC) in response to stimulation with MVA-BN detected by ELISPOT assay.	within 32 weeks