Cytomegalovirus InfectionsPhase 2NCT00125502
Recombinant CMV gB Vaccine in Postpartum Women
A Phase 2 study testing CMV gB vaccine and MF59 adjuvant in people with Cytomegalovirus Infections, run by Robert Pass, MD at 2 sites in United States.
Trial summary
The purpose of this study is to determine if a new cytomegalovirus (CMV) vaccine (CMV gB/MF59) can safely prevent mothers from catching CMV infection between pregnancies. This study includes 464 women, ages 14-40 years, who delivered a newborn infant within 12 months prior to the study. Read more about this study
- Who is it for?
- Ages 14 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cytomegalovirus Infections
- What is being tested?
- CMV gB vaccine and MF59 adjuvant
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 464 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 1999to Jan 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 40 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Mothers, 14 to 40 years of age (inclusive), who have delivered a newborn infant within the previous 12 months, reside within the Birmingham metropolitan area or the Tuscaloosa county area, and sign an informed consent form following a detailed explanation of the study.
- Cytomegalovirus (CMV) seronegative as determined by the Axsym® System CMV IgG antibody assay (Abbott Diagnostics) performed within 14 weeks prior to the first immunization.
- In good health as judged by medical history obtained by patient interview and physical examination.
- Willing to participate with 4 follow-up visits per year for 3 years after the third dose of vaccine.
- Volunteers must be willing to use an effective means of contraception of their choice from the first dose of vaccine up to 2 months after the third dose of the vaccine.
- Methods that were considered effective for the purposes of this clinical trial included any hormonal contraceptive, double barrier methods and abstinence.
Who cannot join
- Known maternal immune disorder such as HIV infection, collagen vascular disease, immune deficiency, or chronic disease requiring treatment with immunosuppressive medication.
- Chronic disease such as diabetes, sickle cell disease, heart disease, fibromyalgia, arthritis or asthma requiring medication.
- Patients with a diagnosis of asthma or past asthma were allowed to enroll if they did not currently take medication for asthma and were off asthma medication and free from asthma symptoms for at least 2 years. Patients with mild to moderate essential hypertension on medication were allowed if their blood pressure was controlled within the normal range for at least one month.
- Positive rapid test for HIV antibody. All subjects were tested for HIV antibody using a rapid serologic test at the time of enrollment beginning with protocol version 1.7. Prior to that only subjects who had a history of a negative screening test for HIV during their most recent pregnancy were included. Subjects given HIV rapid serologic tests in this study were provided pre-test counseling before the test was performed and post-test counseling when the subject was informed of the test results. This counseling is provided by the study nurses according to CDC guidelines [Centers for Disease Control and Prevention. Revised Guidelines for HIV Counseling, Testing and Referral and Revised Recommendations for HIV Screening of Pregnant Women. Subjects who are eligible for this study were considered very unlikely to be HIV positive because almost all adults who are HIV positive are also CMV positive and almost all potential enrollees will have received HIV screening during their recent pregnancy.
- Maternal sterilization procedure planned in the postpartum period.
- Current use of steroids or other immunosuppressive medications.
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- Maternal drug or alcohol abuse.
- Mothers who are nursing their infants.
- Participation in a clinical trial of another investigational vaccine or drug, if they have received the investigational drug or vaccine within 6 months prior to enrollment date for this trial.
- A history of anaphylaxis or serious vaccine reactions.
- Previous receipt of CMV vaccine.
- Receipt of blood products within 3 months prior to study enrollment.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294-3293
University of Alabama at Tuscaloosa
Tuscaloosa, Alabama, 35487
About this study
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Clinical Trial of Recombinant CMV gB Vaccine in Postpartum Women
The purpose of this study is to determine if a new cytomegalovirus (CMV) vaccine (CMV gB/MF59) can safely prevent mothers from catching CMV infection between pregnancies. This study includes 464 women, ages 14-40 years, who delivered a newborn infant within 12 months prior to the study. Participants must live within the Birmingham metropolitan area or the Tuscaloosa county area and they cannot have had CMV infection previously. CMV vaccine or placebo (substance containing no medication) will be given at 3 study visits. Participants fill out diary cards for 7 days after each vaccination. Blood samples will be collected. Urine samples will be collected several times and pregnancy tests will be performed. Participants who tested positive for CMV will have urine, vaginal swab, and saliva specimens collected. Each participant will be followed for 3 years after the third dose of vaccine. Infants born to participants in the study will be checked for CMV infection.
Read the detailed description
The objective of this double-blind, randomized, placebo-controlled Phase II study is to determine whether a recombinant subunit vaccine comprised of cytomegalovirus (CMV) envelope glycoprotein B (gB) with MF59 adjuvant can prevent maternal CMV infection between pregnancies in a high risk population of women of childbearing age. This study will also permit determination of whether the approach used is a feasible one for a large scale efficacy trial with prevention of congenital CMV as the endpoint. CMV gB vaccine is comprised of a recombinant CMV envelope glycoprotein produced in a Chinese hamster ovary cell line. The CMV gB is combined with a novel adjuvant, MF59, a proprietary oil-in-water emulsion. Vaccines will be administered at 0, 1, and 6 months by intramuscular injection in the left deltoid. Placebo recipients will be given a normal saline solution. Study participants were recruited from postpartum wards and from the community. Potential participants were screened for antibody to CMV; those who were seronegative were invited to participate in the vaccine study. Participants received their initial immunization 1.5 to 12 months postpartum. A total of 464, seronegative women who were willing to participate and met enrollment inclusion and exclusion criteria were randomized to 1 of 2 groups: Group I participants received 20 micrograms of gB with MF59; Group II participants received placebo (normal saline). During the immunization period local and systemic reactogenicity was assessed by a 7-day diary card completed after each dose of vaccine. Adverse events are tabulated. Safety is assessed by comparing the local and systemic reactogenicity and adverse event rates between vaccine and placebo recipients. Study participants are screened for CMV infection every three months, beginning three months after the first dose of vaccine, using a CMV IgG antibody assay with preabsorption of sera with purified recombinant CMV gB (vaccine antigen). CMV infection will be confirmed by either isolation of virus or detection of CMV DNA in body fluids. After the 3 dose vaccine schedule has been completed, participants are followed every 3 months. The primary endpoint is the time to CMV infection. The rate of congenital CMV infection in offspring of immunized mothers is a secondary endpoint. The rate of congenital CMV infection will be compared between offspring of vaccine and placebo recipients. Each subject will be followed for 3 years from the third dose of vaccine. Specific information will be collected on the following pregnancy outcomes: pregnancy report, pregnancy follow-up, abnormal pregnancy outcome-mother, and abnormal pregnancy outcome-infant.
- Conditions
- Cytomegalovirus Infections
- Being tested
- CMV gB vaccine, MF59 adjuvant, Placebo
- Keywords
- CMV, Cytomegalovirus, vaccine, women, postpartum
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV gB vaccineBiological
CMV gB is combined with a novel adjuvant, MF59, a proprietary oil-in-water emulsion, administered at 0, 1, and 6 months.
MF59 adjuvantDrug
Oil-in-water emulsion
PlaceboDrug
Normal saline solution
| Study group | Role | What they receive |
|---|---|---|
| I | Experimental | n=200; 20 micrograms gB with MF59 Receives: Biological: CMV gB vaccine; Drug: MF59 adjuvant |
| II | Placebo comparator | n=200; placebo (normal saline) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to CMV infection.
Measured: From initial vaccine to final study visit.
Secondary outcomes (5)
Rate of CMV infection in CMV gB vaccine and placebo recipients.
Measured: From initial vaccine to final study visit.
Rate of congenital CMV infection in offspring of the immunized women.
Measured: From initial vaccine to final study visit.
Rate of local and systemic reactions and adverse events.
Measured: Duration of study.
Peak levels of antibody to CMV gB and neutralizing antibody and decline in antibody levels over time.
Measured: 2 weeks post third dose of vaccine and decline over time up to 3 years post-third dose of vaccine.
Lymphocyte proliferation response to gB.
Measured: From 3 months post-third dose of vaccine to study termination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2005 (estimated)
- Study startAug 1999
- Primary completionJun 2007
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 464 participants (actual)
Sponsor and investigators
- Lead sponsor
- Robert Pass, MD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), MCM Vaccines B.V.
- Responsible party
- Sponsor-investigator, Robert Pass, MD, University of Alabama at Birmingham
- Investigators
- Robert F Pass, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00125502
- Sponsor's protocol ID
- 99-038
- Other IDs
- U01AI063565, sanofi pasteur CMC00
- Status last verified
- Sep 2011
- First submitted
- 29 Jul 2005
- Last updated
- 20 Sep 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pass RF, Zhang C, Evans A, Simpson T, Andrews W, Huang ML, Corey L, Hill J, Davis E, Flanigan C, Cloud G. Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med. 2009 Mar 19;360(12):1191-9. doi: 10.1056/NEJMoa0804749.
PubMed 19297572
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Double-Blind, Placebo-Controlled, Clinical Trial of Recombinant CMV gB Vaccine in Postpartum Women
- ClinicalTrials.gov ID
- NCT00125502
- Acronym / sponsor ID
- 99-038
- Conditions
- Cytomegalovirus Infections
- Keywords
- CMV, Cytomegalovirus, vaccine, women, postpartum
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 464 participants (actual)
- Lead sponsor
- Robert Pass, MDUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), MCM Vaccines B.V.
- Study start
- Aug 1999
- Primary completion
- Jun 2007 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 1 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if a new cytomegalovirus (CMV) vaccine (CMV gB/MF59) can safely prevent mothers from catching CMV infection between pregnancies. This study includes 464 women, ages 14-40 years, who delivered a newborn infant within 12 months prior to the study. Participants must live within the Birmingham metropolitan area or the Tuscaloosa county area and they cannot have had CMV infection previously. CMV vaccine or placebo (substance containing no medication) will be given at 3 study visits. Participants fill out diary cards for 7 days after each vaccination. Blood samples will be collected. Urine samples will be collected several times and pregnancy tests will be performed. Participants who tested positive for CMV will have urine, vaginal swab, and saliva specimens collected. Each participant will be followed for 3 years after the third dose of vaccine. Infants born to participants in the study will be checked for CMV infection.
Detailed description
The objective of this double-blind, randomized, placebo-controlled Phase II study is to determine whether a recombinant subunit vaccine comprised of cytomegalovirus (CMV) envelope glycoprotein B (gB) with MF59 adjuvant can prevent maternal CMV infection between pregnancies in a high risk population of women of childbearing age. This study will also permit determination of whether the approach used is a feasible one for a large scale efficacy trial with prevention of congenital CMV as the endpoint. CMV gB vaccine is comprised of a recombinant CMV envelope glycoprotein produced in a Chinese hamster ovary cell line. The CMV gB is combined with a novel adjuvant, MF59, a proprietary oil-in-water emulsion. Vaccines will be administered at 0, 1, and 6 months by intramuscular injection in the left deltoid. Placebo recipients will be given a normal saline solution. Study participants were recruited from postpartum wards and from the community. Potential participants were screened for antibody to CMV; those who were seronegative were invited to participate in the vaccine study. Participants received their initial immunization 1.5 to 12 months postpartum. A total of 464, seronegative women who were willing to participate and met enrollment inclusion and exclusion criteria were randomized to 1 of 2 groups: Group I participants received 20 micrograms of gB with MF59; Group II participants received placebo (normal saline). During the immunization period local and systemic reactogenicity was assessed by a 7-day diary card completed after each dose of vaccine. Adverse events are tabulated. Safety is assessed by comparing the local and systemic reactogenicity and adverse event rates between vaccine and placebo recipients. Study participants are screened for CMV infection every three months, beginning three months after the first dose of vaccine, using a CMV IgG antibody assay with preabsorption of sera with purified recombinant CMV gB (vaccine antigen). CMV infection will be confirmed by either isolation of virus or detection of CMV DNA in body fluids. After the 3 dose vaccine schedule has been completed, participants are followed every 3 months. The primary endpoint is the time to CMV infection. The rate of congenital CMV infection in offspring of immunized mothers is a secondary endpoint. The rate of congenital CMV infection will be compared between offspring of vaccine and placebo recipients. Each subject will be followed for 3 years from the third dose of vaccine. Specific information will be collected on the following pregnancy outcomes: pregnancy report, pregnancy follow-up, abnormal pregnancy outcome-mother, and abnormal pregnancy outcome-infant.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| I | Experimental | Biological: CMV gB vaccine, Drug: MF59 adjuvantn=200; 20 micrograms gB with MF59 |
| II | Placebo comparator | Drug: Placebon=200; placebo (normal saline) |
Who may qualify
- Ages
- 14 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Mothers, 14 to 40 years of age (inclusive), who have delivered a newborn infant within the previous 12 months, reside within the Birmingham metropolitan area or the Tuscaloosa county area, and sign an informed consent form following a detailed explanation of the study.
- Cytomegalovirus (CMV) seronegative as determined by the Axsym® System CMV IgG antibody assay (Abbott Diagnostics) performed within 14 weeks prior to the first immunization.
- In good health as judged by medical history obtained by patient interview and physical examination.
- Willing to participate with 4 follow-up visits per year for 3 years after the third dose of vaccine.
- Volunteers must be willing to use an effective means of contraception of their choice from the first dose of vaccine up to 2 months after the third dose of the vaccine.
Key exclusion criteria (12 listed)
- Known maternal immune disorder such as HIV infection, collagen vascular disease, immune deficiency, or chronic disease requiring treatment with immunosuppressive medication.
- Chronic disease such as diabetes, sickle cell disease, heart disease, fibromyalgia, arthritis or asthma requiring medication.
- Patients with a diagnosis of asthma or past asthma were allowed to enroll if they did not currently take medication for asthma and were off asthma medication and free from asthma symptoms for at least 2 years. Patients with mild to moderate essential hypertension on medication were allowed if their blood pressure was controlled within the normal range for at least one month.
- Positive rapid test for HIV antibody. All subjects were tested for HIV antibody using a rapid serologic test at the time of enrollment beginning with protocol version 1.7. Prior to that only subjects who had a history of a negative screening test for HIV during their most recent pregnancy were included. Subjects given HIV rapid serologic tests in this study were provided pre-test counseling before the test was performed and post-test counseling when the subject was informed of the test results. This counseling is provided by the study nurses according to CDC guidelines [Centers for Disease Control and Prevention. Revised Guidelines for HIV Counseling, Testing and Referral and Revised Recommendations for HIV Screening of Pregnant Women. Subjects who are eligible for this study were considered very unlikely to be HIV positive because almost all adults who are HIV positive are also CMV positive and almost all potential enrollees will have received HIV screening during their recent pregnancy.
- Maternal sterilization procedure planned in the postpartum period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CMV gB vaccineCMV gB is combined with a novel adjuvant, MF59, a proprietary oil-in-water emulsion, administered at 0, 1, and 6 months. | Biological | I |
| MF59 adjuvantOil-in-water emulsion | Drug | I |
| PlaceboNormal saline solution | Drug | II |
Primary outcome
Time to CMV infection.
Time frame: From initial vaccine to final study visit.
5 secondary outcomes
Rate of CMV infection in CMV gB vaccine and placebo recipients.
Time frame: From initial vaccine to final study visit.
Rate of congenital CMV infection in offspring of the immunized women.
Time frame: From initial vaccine to final study visit.
Rate of local and systemic reactions and adverse events.
Time frame: Duration of study.
Peak levels of antibody to CMV gB and neutralizing antibody and decline in antibody levels over time.
Time frame: 2 weeks post third dose of vaccine and decline over time up to 3 years post-third dose of vaccine.
Lymphocyte proliferation response to gB.
Time frame: From 3 months post-third dose of vaccine to study termination.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2011.
- Derived from this study: PubMed 19297572Pass RF, Zhang C, Evans A, Simpson T, Andrews W, Huang ML, Corey L, Hill J, Davis E, Flanigan C, Cloud G. Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med. 2009 Mar 19;360(12):1191-9. doi: 10.1056/NEJMoa0804749.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert F Pass, MD principal investigator
University of Alabama at Birmingham
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CMV gB vaccine and MF59 adjuvant in people with Cytomegalovirus Infections, run by Robert Pass, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to CMV infection. (time frame: From initial vaccine to final study visit.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00125502, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2011.