Common Variable Immune DeficiencyNCT02960399
Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older
A study testing Zostavax® in people with Common Variable Immune Deficiency and Specific Antibody Deficiency, run by University of South Florida at 1 site in United States.
Trial summary
Recommendations concerning the administration of Zostavax® in patients with antibody deficiency are unclear. The investigators plan to assess the immunogenicity and safety of Zostavax® in patients with antibody deficiency as compared with healthy volunteers. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Common Variable Immune Deficiency, Specific Antibody Deficiency, X-linked Agammaglobulinemia
- What is being tested?
- Zostavax®
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Dec 2017
- Phase
- Interventional
- 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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults 60 years of age and older
- Diagnosis of common variable immunodeficiency (CVID), Specific Antibody Deficiency (SAD), or X-linked agammaglobulinemia (XLA)
- Receiving replacement gammaglobulin
- Willing and able to sign consent and follow study schedule
- History of varicella or long-term (greater than or equal to 30 years) residence in the USA
- Adults 60 years of age and older
- Willing and able to sign consent and follow study schedule
- History of varicella or long-term (greater than or equal to 30 years) residence in the USA
Who cannot join
- Allergy to Zostavax® or any of its components (i.e gelatin, neomycin)
- Absolute CD3, CD4, or CD8 lymphopenia as determined by age specific reference ranges
- Poor T cell function as indicated by a < 30 % increase in T cell response to mitogens or antigens as compared to the age matched normal reference range (in CVID) subjects
- Evidence of acute systemic illness or infection at within four weeks of screening or enrollment
- Prior herpes zoster infection
- Previously received herpes zoster vaccination
Show all 30Show fewer
- Malignancy including solid tumors, leukemia, or lymphoma
- Presence of autoimmune or other inflammatory disease
- Use of immunosuppressive or immunomodulatory medications including chronic corticosteroids. Treatment for >2weeks of daily steroids will be considered chronic use.
- History of bleeding or chronic skin disorders.
- Pregnant or breastfeeding females
- Immunizations within one month
- Persons with HIV or AIDS
- Subject unwilling to sign consent or adhere to study schedule
- Any condition that in the opinion of the investigator would interfere with the conduct of the study
- Subjects unlikely to adhere to protocol follow-up
- Allergy to Zostavax® or any of its components (i.e gelatin, neomycin)
- Evidence of acute systemic illness or infection at within four weeks of screening or enrollment
- Prior herpes zoster infection
- Previously received herpes zoster vaccination
- Malignancy including solid tumors, leukemia, or lymphoma
- Presence of autoimmune or other inflammatory disease
- Use of immunosuppressive or immunomodulatory medications including chronic corticosteroids. Treatment for >2weeks of daily steroids will be considered chronic use.
- History of bleeding or chronic skin disorders.
- Pregnant or breastfeeding females
- Immunizations within one month
- Persons with HIV or AIDS
- Subject unwilling to sign consent or adhere to study schedule
- Any condition that in the opinion of the investigator would interfere with the conduct of the study
- Subjects unlikely to adhere to protocol follow-up
Trial locations and contacts
1 site in 1 country.
United States1 site
University of South Florida
St. Petersburg, Florida, 33701
About this study
Recommendations concerning the administration of Zostavax® in patients with antibody deficiency are unclear. The investigators plan to assess the immunogenicity and safety of Zostavax® in patients with antibody deficiency as compared with healthy volunteers.
Read the detailed description
Common variable immune deficiency (CVID), specific antibody deficiency (SAD), and X-linked agammaglobulinemia (XLA) are among the most common primary antibody deficiencies in which the mainstay of treatment is gammaglobulin replacement. The use of high doses of immunoglobulin replacement therapy and the early recognition of co-morbid diseases during the course of CVID, SAD, and XLA has improved survival and led to an aging population of CVID, SAD, and XLA patients.
The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of all persons aged >60 years with 1 dose of vaccine directed against herpes zoster (Zostavax®) in the absence of any contraindications. Current standard of care includes avoidance of all vaccines when receiving gammaglobulin products due to passive immunity obtained from gammaglobulin against vaccine preventable infections. The exception to this rule is that patients on gammaglobulin should receive the yearly influenza vaccine due to its enhanced cell mediated immunity against the influenza virus. Clinical immunologists currently have no data upon which to advise patients receiving gammaglobulin replacement including those with CVID, SAD, and XLA concerning use of Zostavax®.
All gammaglobulin replacement products maintain protective antibody levels against VZV. However, humoral immune responses with anti-VZV antibodies are relatively constant and do not protect against the development of shingles. Varicella zoster virus specific cell mediated immunity (VZV-CMI), which is T cell dependent, is the critical component in preventing herpes zoster (shingles). VZV-CMI diminishes with age leaving the elderly most susceptible to shingles. Several studies have concluded that boosting VZV-CMI protects older adults from developing herpes zoster and postherpetic neuralgia (PHN).
Recommendations on the prevention of herpes zoster published in the Morbidity and Mortality Weekly Report (MMWR) by the Centers for disease control (CDC) in May 2008 make the following statements:
- Zoster vaccine should not be administered to persons with primary or acquired immunodeficiency including:
- Persons with clinical or laboratory evidence of other unspecified cellular immunodeficiency.
- Persons with impaired humoral immunity (e.g., hypogammaglobulinemia or dysgammaglobulinemia) can/should receive zoster vaccine.
The investigators hypothesize that vaccination with Zostavax® in adults with CVID, SAD, and XLA who have evidence of normal cell mediated immunity with normal T cell quantities and function will have a boost in VZV-CMI thereby reducing susceptibility to shingles and PHN.
Successful completion of this study will provide clinical immunologists with data upon which to advise antibody deficient patients concerning the use of Zostavax®.
- Conditions
- Common Variable Immune Deficiency, Specific Antibody Deficiency, X-linked Agammaglobulinemia
- Being tested
- Zostavax®
- Medical subject headings
- Common Variable Immunodeficiency, Bruton type agammaglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zostavax®Biological
Zostavax® immunization
| Study group | Role | What they receive |
|---|---|---|
| Antibody Deficient Patients | Experimental | Zostavax® vaccine administered to antibody deficient patients 60 years of age and older. Receives: Biological: Zostavax® |
| Healthy Subjects | Active comparator | Zostavax® vaccine administered per standard of care to healthy adults 60 years of age and older. Receives: Biological: Zostavax® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine in vitro changes in T cell proliferation preceding and following vaccination with Zostavax® by measurement of lymphocyte proliferation in response to VZV antigen.
Determine in vitro lymphocyte proliferation as counts per minute after stimulation of cells with varicella zoster antigen at time points preceding and following vaccination with Zostavax. Blood samples will be obtained prior to administering the Zostavax® vaccine and post-vaccination at 4 weeks, 3 months, and 6 months.
Measured: Day 0, Week 4, 3 months, 6 months
Secondary outcomes (1)
Determine in vitro changes in T cell proliferation preceding and following vaccination with Zostavax® by measurement of IFNg production by T cells in response to VZV antigen.
Determine in vitro IFNg production as Units/ml after stimulation of cells with varicella zoster antigen at time points preceding and following vaccination with Zostavax. Blood samples will be obtained prior to administering the Zostavax® vaccine and post-vaccination at 4 weeks, 3 months, and 6 months.
Measured: Day 0, Week 4, 3 months, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2016 (estimated)
- Study startDec 2015
- Primary completionDec 2017
- Study completionDec 2017
Why it stopped: PI has terminated the study at this time.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Common Variable Immune DeficiencyStudies of the same condition, open and under way.
- More trials run by University of South FloridaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of South Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Jennifer Leiding, MD, Principal investigator, University of South Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02960399
- Sponsor's protocol ID
- Pro00023706
- Status last verified
- Apr 2018
- First submitted
- 3 Oct 2016
- Last updated
- 31 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older
- ClinicalTrials.gov ID
- NCT02960399
- Acronym / sponsor ID
- Pro00023706
- Conditions
- Common Variable Immune Deficiency, Specific Antibody Deficiency, X-linked Agammaglobulinemia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI has terminated the study at this time.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of South FloridaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Dec 2015
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 9 Nov 2016 (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.
Recommendations concerning the administration of Zostavax® in patients with antibody deficiency are unclear. The investigators plan to assess the immunogenicity and safety of Zostavax® in patients with antibody deficiency as compared with healthy volunteers.
Detailed description
Common variable immune deficiency (CVID), specific antibody deficiency (SAD), and X-linked agammaglobulinemia (XLA) are among the most common primary antibody deficiencies in which the mainstay of treatment is gammaglobulin replacement. The use of high doses of immunoglobulin replacement therapy and the early recognition of co-morbid diseases during the course of CVID, SAD, and XLA has improved survival and led to an aging population of CVID, SAD, and XLA patients.
The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of all persons aged >60 years with 1 dose of vaccine directed against herpes zoster (Zostavax®) in the absence of any contraindications. Current standard of care includes avoidance of all vaccines when receiving gammaglobulin products due to passive immunity obtained from gammaglobulin against vaccine preventable infections. The exception to this rule is that patients on gammaglobulin should receive the yearly influenza vaccine due to its enhanced cell mediated immunity against the influenza virus. Clinical immunologists currently have no data upon which to advise patients receiving gammaglobulin replacement including those with CVID, SAD, and XLA concerning use of Zostavax®.
All gammaglobulin replacement products maintain protective antibody levels against VZV. However, humoral immune responses with anti-VZV antibodies are relatively constant and do not protect against the development of shingles. Varicella zoster virus specific cell mediated immunity (VZV-CMI), which is T cell dependent, is the critical component in preventing herpes zoster (shingles). VZV-CMI diminishes with age leaving the elderly most susceptible to shingles. Several studies have concluded that boosting VZV-CMI protects older adults from developing herpes zoster and postherpetic neuralgia (PHN).
Recommendations on the prevention of herpes zoster published in the Morbidity and Mortality Weekly Report (MMWR) by the Centers for disease control (CDC) in May 2008 make the following statements:
- Zoster vaccine should not be administered to persons with primary or acquired immunodeficiency including:
- Persons with clinical or laboratory evidence of other unspecified cellular immunodeficiency.
- Persons with impaired humoral immunity (e.g., hypogammaglobulinemia or dysgammaglobulinemia) can/should receive zoster vaccine.
The investigators hypothesize that vaccination with Zostavax® in adults with CVID, SAD, and XLA who have evidence of normal cell mediated immunity with normal T cell quantities and function will have a boost in VZV-CMI thereby reducing susceptibility to shingles and PHN.
Successful completion of this study will provide clinical immunologists with data upon which to advise antibody deficient patients concerning the use of Zostavax®.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Antibody Deficient Patients | Experimental | Biological: Zostavax®Zostavax® vaccine administered to antibody deficient patients 60 years of age and older. |
| Healthy Subjects | Active comparator | Biological: Zostavax®Zostavax® vaccine administered per standard of care to healthy adults 60 years of age and older. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adults 60 years of age and older
- Diagnosis of common variable immunodeficiency (CVID), Specific Antibody Deficiency (SAD), or X-linked agammaglobulinemia (XLA)
- Receiving replacement gammaglobulin
- Willing and able to sign consent and follow study schedule
- History of varicella or long-term (greater than or equal to 30 years) residence in the USA
Key exclusion criteria (30 listed)
- Allergy to Zostavax® or any of its components (i.e gelatin, neomycin)
- Absolute CD3, CD4, or CD8 lymphopenia as determined by age specific reference ranges
- Poor T cell function as indicated by a < 30 % increase in T cell response to mitogens or antigens as compared to the age matched normal reference range (in CVID) subjects
- Evidence of acute systemic illness or infection at within four weeks of screening or enrollment
- Prior herpes zoster infection
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 |
|---|---|---|
| Zostavax®Zostavax® immunization | Biological | Antibody Deficient Patients, Healthy Subjects |
Primary outcome
Determine in vitro changes in T cell proliferation preceding and following vaccination with Zostavax® by measurement of lymphocyte proliferation in response to VZV antigen.
Time frame: Day 0, Week 4, 3 months, 6 months
Determine in vitro lymphocyte proliferation as counts per minute after stimulation of cells with varicella zoster antigen at time points preceding and following vaccination with Zostavax. Blood samples will be obtained prior to administering the Zostavax® vaccine and post-vaccination at 4 weeks, 3 months, and 6 months.
1 secondary outcome
Determine in vitro changes in T cell proliferation preceding and following vaccination with Zostavax® by measurement of IFNg production by T cells in response to VZV antigen.
Time frame: Day 0, Week 4, 3 months, 6 months
Results and safety
The study was stopped early (reason given: PI has terminated the study at this time.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2018.
- Individual participant dataSharing planned: Undecided
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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.
Jennifer Leiding, MD principal investigator
University of South Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Zostavax® in people with Common Variable Immune Deficiency and Specific Antibody Deficiency, run by University of South Florida at 1 site 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 8 inclusion and 30 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: stopped early, as of the sponsor's last update on 31 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: PI has terminated the study at this time.). Results are not available in the source record.
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?
Determine in vitro changes in T cell proliferation preceding and following vaccination with Zostavax® by measurement of lymphocyte proliferation in response to VZV antigen. (time frame: Day 0, Week 4, 3 months, 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 May 2018.