gB/MF59 Vaccine in Preventing Cytomegalovirus Infection in Healthy Adolescent Females

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study to Assess the Safety and Efficacy of the Cytomegalovirus gB/MF59 Vaccine in Preventing Systemic Cytomegalovirus Infection in Healthy Adolescent Females

The purpose of this research study is to test the safety of and the body's response to an experimental cytomegalovirus (CMV) vaccine (called gB/MF59 vaccine). Participants will include approximately 400 healthy females, ages 12-17, recruited from adolescent clinics at Cincinnati Children's Hospital Medical Center, Vanderbilt University Medical Center, Baylor College of Medicine, University of Texas School of Public Health, Houston, and the University of Texas Medical Branch at Galveston. Participants will receive 3 doses of vaccine or placebo (saltwater) on a 0, 1, and 6 month schedule. Study procedures will include blood and urine samples. Participants will complete a diary recording temperatures and any side effects experienced. Subjects will be involved in study related procedures for up to 31 months.

Study Overview

Detailed Description

This is a randomized, double-blind, placebo-controlled, phase II study to assess the safety and efficacy of the cytomegalovirus glycoprotein B (gB)/MF59 vaccine in preventing systemic cytomegalovirus infection (CMV) in healthy adolescent females. The study interventions include: intramuscular (IM) injection of the investigational vaccine, CMV gB)/microfluidized adjuvant 59 (MF59), delivered as 20 micrograms in 0.5 mL of vaccine or IM injection of 0.5 mL of saline placebo. Subjects will be randomized (1:1) to receive vaccine or saline placebo. The primary efficacy objective is to assess whether injection with 3 doses of the CMV gB/MF59 vaccine will reduce the acquisition of a systemic CMV infection in healthy CMV-seronegative adolescent females. This will be accomplished by comparing the rates of acquisition of systemic CMV infection, defined as detection of CMV in the urine or blood, between the placebo and CMV vaccine recipients beginning 1 month after the third dose of vaccine. The primary safety objective is to assess the local and systemic effects of immunization and adverse events (AE) with the CMV gB/MF59 vaccine when administered to female adolescents on a 0-, 1-, and 6-month schedule. This will be assessed by comparing the rates of specific local and systemic reactogenicity events and AEs between the vaccine and placebo groups. The endpoint for this trial will be a systemic infection, which will be defined as identification of CMV from the urine (chosen because it is the most common site for isolation of CMV) or blood (chosen because it is the most likely route by which CMV reaches the fetus). Approximately 2400 healthy females, age 12 to 17 years (at time of initial enrollment) will be recruited in order to obtain approximately 400 CMV-seronegative subjects for the vaccine trial. Collection of sera will occur at Screening, Study Day 0, Month 6, Month 7 and every 3 months after Month 7. Collection of urine will occur at Study Day 0, Month 1, Month 2, Month 6, Month 7 and every 3 months after Month 7. Safety/reactogenicity monitoring will consist of solicited signs and symptoms self-reported by memory aid on the day of vaccination and for 6 follow-up days. Unsolicited symptoms will be collected for the 30-day period (± 2 days) after each vaccination and followed to adequate resolution or stabilization. The study duration for each subject will be 31 months: 7 months on the study with 24 months of follow-up beginning 1 month after the last injection. There will be 14 scheduled visits. This study is linked to DMID protocol 06-0043.

Study Type

Interventional

Enrollment (Actual)

409

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ohio
      • Cincinnati, Ohio, United States, 45229-3026
        • Cincinnati Children's Hospital Medical Center - Infectious Diseases
    • Tennessee
      • Nashville, Tennessee, United States, 37232-2573
        • Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
    • Texas
      • Galveston, Texas, United States, 77555-1121
        • The University of Texas Medical Branch - Sealy Center for Vaccine Development (SCVD)
      • Houston, Texas, United States, 77030-3411
        • Baylor College of Medicine - Molecular Virology and Microbiology
      • Houston, Texas, United States, 77030-1501
        • The University of Texas Health Science Center - Pediatrics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 17 years (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

Subject Inclusion Criteria (Screening):

  • Subjects must be willing and able to provide written informed assent prior to study enrollment; parent(s) or legal guardian must provide written informed consent prior to study enrollment.
  • Subjects must be female and be 12 to 17 years at time of screening.
  • Subjects must be willing to consider participation in the experimental cytomegalovirus (CMV) vaccine portion of the study which is 31-months in duration and must not be planning to relocate from the study area.
  • Subjects must be using or willing to consider using effective methods of birth control. This includes abstinence or if sexually active using an effective method of birth control (e.g., oral contraceptives; diaphragm or condom in combination with contraceptive jelly; cream or foam; intrauterine contraceptive device; Depo-Provera®; skin patch; vaginal ring or cervical cap) for 30 days prior to vaccination and must agree to continue such precautions for 3 months after completion of the vaccination series.
  • Subjects who are of childbearing potential must be willing to have a urine or serum pregnancy test within 24 hours before vaccination. The results will need to be negative to enroll in the vaccine study.

Subject's inclusion criteria (vaccine):

  • Subject is willing and able to provide written informed assent prior to study enrollment; parent(s) or legal guardian provides written informed consent prior to study enrollment.
  • Subject is female and 12 to 17 years at time of screening.
  • Subject is available for the 31-month duration of the study (7 months on the study and 24 months of follow-up beginning 1 month after the last injection) and is not planning to relocate from the study area.
  • Subject must agree to practice abstinence, or if sexually active must be using an effective method of birth control (e.g., oral contraceptives; diaphragm or condom in combination with contraceptive jelly; cream or foam; intrauterine contraceptive device; Depo-Provera®; skin patch; vaginal ring or cervical cap) for 30 days prior to vaccination and must agree to continue such precautions for 3 months after completion of the vaccination series.
  • Subject of child bearing potential has a negative urine or serum pregnancy test within 24 hours of vaccination.
  • Subject is willing and able to comply with the requirements of the protocol (e.g., completion of the memory aid, return for follow-up visits, accessible by phone and not planning on moving from the study area).

Subject Inclusion Criteria (Shedding):

  • Subjects must be willing and able to provide written informed assent prior to study enrollment; parent(s) or legal guardian must provide written informed consent prior to study enrollment.
  • Subject is positive for antibodies to CMV detected by enzyme-linked immunosorbent assay (ELISA) using a commercial CMV antibody assay screen.
  • Subjects must be willing and able to comply with the requirements of the protocol (e.g., completion of the visits, accessible by phone and not planning on moving from the study area).

Exclusion Criteria:

Subject Exclusion Criteria (Screening):

  • Receipt of blood and/or blood products in the past 3 months
  • Known to be pregnant or lactating
  • Planning to become pregnant during the first 8 months of the study (Months 0-8);
  • Known previous infection with cytomegalovirus (CMV);
  • Previously received a CMV vaccine;
  • History of allergic reactions to any component of the study vaccine;
  • History of malignancy or have a confirmed or suspected immunodeficient condition, such as human immunodeficiency virus (HIV) infection;
  • History of current acute or chronic autoimmune disease;
  • History of ongoing clinically significant illness (diabetes, pulmonary, cardiovascular, hepatic or renal functional abnormality) as determined by medical history;
  • History of any neurologic disorders or seizures, with the exception of febrile seizures during childhood;
  • Presently receiving or history of receiving any medications or treatments that affect the immune system such as immune globulin, interferon, immunomodulators, cytotoxic drugs or drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable) in the past 6 months. Inhaled and topical corticosteroids will be allowed;
  • History of depression not controlled with current drug therapy or involving institutionalization;
  • History of schizophrenia or psychosis;
  • History of suicide attempt;
  • Active substance or alcohol abuse;
  • Currently enrolled in another research study. (Subjects participating in a non-interventional studies, questionnaires, or observational studies will not be excluded from participation).

Subjects exclusion criteria (vaccine):

  • Antibodies to CMV that are detected at the screening visit;
  • Previously received a CMV vaccine;
  • Subject is planning on becoming pregnant during the first 8 months of the vaccine study;
  • Subject receives an experimental drug or vaccine in the 30 days prior to the first dose of vaccine or planned receipt before 30 days after the final dose of the vaccine;
  • Subject receives or is planning to receive a nonstudy vaccine within 30 days before or after any dose of study vaccine with the following exceptions: Administration of routine meningococcal, hepatitis A, hepatitis B, Tdap (Tetanus, Diphtheria, Pertussis), human papillomavirus (HPV), inactivated influenza (but not FluMist®), diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before or at least 8 days after a dose of study vaccine is allowed. Administration of vaccine injection can be delayed if a nonstudy vaccine has been administered and will be given as soon as acceptable;
  • Subject has an acute disease within 72 hours prior to enrollment in the vaccine study, defined as the presence of a moderate or severe illness (as determined by the investigator through medical history and physical examination. Study vaccine can be administered to persons with a minor illness, such as diarrhea, or mild upper respiratory tract infection with or without low-grade febrile illness. Vaccination can be delayed until the subject has recovered;
  • Subject receives systemic corticosteroids > 2mg/kg for >14 days. Inhaled and topical steroids are permitted.

Subject Exclusion Criteria (Shedding):

None

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 20 mcg CMV gB + MF59
200 subjects will receive vaccine CMV gB + MF59.
Microfluoridized adjuvant 59 (MF59).
CMV glycoprotein B (gB) delivered as 20 mcg in 0.5 mL of vaccine.
PLACEBO_COMPARATOR: Saline
200 subjects will receive saline placebo.
0.5 mL of saline placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy: systemic cytomegalovirus (CMV) infection, defined by the detection of CMV in the urine or blood, which will be evaluated by CMV detection by polymerase chain reaction (PCR).
Time Frame: Study Day 0, Month 1, Month 2, Month 6, Month 7 and every 3 months after Month 7.
Study Day 0, Month 1, Month 2, Month 6, Month 7 and every 3 months after Month 7.
Safety: incidence of local and systemic reactions, as determined by self-reported assessments using a memory aid, adverse events (AEs) and serious adverse events (SAEs).
Time Frame: Local and systemic reactions within 7 days of vaccination; adverse events (AEs) within the 30 day period after vaccination; serious adverse events (SAEs) observed any time throughout the duration of study.
Local and systemic reactions within 7 days of vaccination; adverse events (AEs) within the 30 day period after vaccination; serious adverse events (SAEs) observed any time throughout the duration of study.

Secondary Outcome Measures

Outcome Measure
Time Frame
Efficacy: CMV infections defined as seroconversion to nonvaccine CMV antigens or identification of CMV in the blood or urine.
Time Frame: Specimens collected every 3 months.
Specimens collected every 3 months.
Immunologic: CMV antibody measurements by CMV neutralization, enzyme-linked immunosorbent assay (ELISA), and CMV glycoprotein B (gB) assay.
Time Frame: Study Day 0, Month 6, Month 7 and every 3 months after Month 7.
Study Day 0, Month 6, Month 7 and every 3 months after Month 7.
Duration and magnitude of CMV replication in the urine and blood as determined from specimens.
Time Frame: Obtained monthly for 4 months and then every other month for 8 months after identification of CMV infection.
Obtained monthly for 4 months and then every other month for 8 months after identification of CMV infection.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (ACTUAL)

June 1, 2013

Study Completion (ACTUAL)

June 1, 2013

Study Registration Dates

First Submitted

August 19, 2005

First Submitted That Met QC Criteria

August 19, 2005

First Posted (ESTIMATE)

August 23, 2005

Study Record Updates

Last Update Posted (ACTUAL)

July 6, 2017

Last Update Submitted That Met QC Criteria

July 3, 2017

Last Verified

September 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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