Herpes ZosterPhase 2NCT01527383
A Study to Evaluate the Safety and Immunogenicity of Inactivated Varicella Zoster Virus (VZV) Vaccine in Adults With Autoimmune Disease (V212-009)
A Phase 2 study testing V212 in people with Herpes Zoster, run by Merck Sharp & Dohme LLC.
Trial summary
This is a study to evaluate the safety and immunogenicity of V212 vaccine in adults with autoimmune disease, including participants with rheumatoid arthritis, psoriatic arthritis, psoriasis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, and other similar diseases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Herpes Zoster
- What is being tested?
- V212
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 354 participants
- Where
- No sites listed yet
- Study dates
- 21 Feb 2012to 26 Feb 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with an autoimmune disease
- Clinically stable disease for at least 30 days before enrollment
- Not likely to undergo hematopoietic stem cell transplantation during the study period
- Receiving at least one parenteral or oral biologic agent, such as a Tumor Necrosis factor (TNF) alpha inhibitor, or a parenteral or oral non-biologic therapy, at a stable dose for at least 3 months, with no planned or anticipated changes
- History of varicella, antibodies to VZV, or residence for at least 30 years in a country with endemic VZV infection, or if participant is less than 30 years old, attended primary or secondary school in a country with endemic VZV infection
Who cannot join
- Prior history of Herpes Zoster (shingles) within 1 year before enrollment
- Prior varicella or zoster vaccine
- Active central nervous system lupus erythematosus requiring therapeutic intervention within 90 days of enrollment
- Prior or planned therapy containing rituximab or other anti-Cluster of Differentiation (CD) 20 monoclonal antibodies from 3 months before enrollment through 28 days postdose 4
- Systemic corticosteroid therapy, prednisone, or equivalent over 40 mg daily at the time of enrollment
About this study
Official title: A Phase II Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Immunogenicity of V212 in Adult Patients With Autoimmune Disease
This is a study to evaluate the safety and immunogenicity of V212 vaccine in adults with autoimmune disease, including participants with rheumatoid arthritis, psoriatic arthritis, psoriasis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, and other similar diseases. The primary hypothesis is that vaccination with V212 vaccine will elicit significant VZV-specific immune responses at approximately 28 days after vaccination 4. The statistical criterion for significance requires that the lower bound of the 2-sided 95% confidence interval of the geometric mean fold rise in vaccine recipients is >1.0.
- Conditions
- Herpes Zoster
- Being tested
- V212, Placebo
- Keywords
- Shingles
- Medical subject headings
- Herpes Zoster
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
V212Biological
Also called Inactivated Varicella-Zoster (VZV) vaccine
V212 viral antigen for HZ
PlaceboBiological
Placebo comparator to V212 vaccine
| Study group | Role | What they receive |
|---|---|---|
| V212 | Experimental | Participants receive V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. Receives: Biological: V212 |
| Placebo | Placebo comparator | Participants receive placebo as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA)
Serum samples were tested for antibody response using a gpELISA. The GMFR is response at approximately 28 days postdose 4 / response predose on Day 1.
Measured: Baseline and ~28 days after Vaccination 4 (~Day 118)
GMFR in VZV Antibody Response Measured by VZV Interferon-gamma (IFN-g) Enzyme-linked Immunospot (ELISPOT) Assay
Serum samples were tested for activity using a VZV ELISPOT assay. The assay detects IFN-γ-secreting, VZV-specific cells from peripheral blood mononuclear cells (PBMCs). The unit of measure of the assay is ELISPOT cell count / 10^6 PBMCs, and is expressed as geometric mean count (GMC). The GMFR is GMC at ~28 days after Vaccination 4 / GMC predose on Day 1.
Measured: Baseline and ~28 days after Vaccination 4 (~Day 118)
Percentage of Participants With a Serious Adverse Event
A serious adverse event (SAE) is defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants with one or more SAE was assessed.
Measured: Up to ~28 days after Vaccination 4 (~Day 118)
Secondary outcomes (3)
Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Vaccination Report Card (VRC)-prompted injection-site AEs were erythema, pain, and swelling. The percentage of participants with one or more VRC-prompted injection-site AE was assessed.
Measured: Up to Day 5 after any vaccination
Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. VRC-prompted systemic AEs included non-injection-site varicella-like and HZ-like rashes. The percentage of participants with one or more VRC-prompted systemic AE was assessed.
Measured: Up to ~28 days after Vaccination 4 (~Day 118)
Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card
Elevated temperature is defined as ≥100.4 °F (≥38.0 °C), oral equivalent. The percentage of participants with VRC-prompted elevated temperature was assessed.
Measured: Up to ~28 days after Vaccination 4 (~Day 118)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2012 (estimated)
- Study start21 Feb 2012
- Primary completion26 Feb 2013
- Study completion26 Feb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Herpes ZosterStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 354 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01527383
- Sponsor's protocol ID
- V212-009
- Other IDs
- V212-009, 2011-002313-11
- Status last verified
- Jan 2019
- First submitted
- 16 Jan 2012
- Last updated
- 14 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Eberhardson M, Hall S, Papp KA, Sterling TM, Stek JE, Pang L, Zhao Y, Parrino J, Popmihajlov Z. Safety and Immunogenicity of Inactivated Varicella-Zoster Virus Vaccine in Adults With Autoimmune Disease: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Clin Infect Dis. 2017 Oct 1;65(7):1174-1182. doi: 10.1093/cid/cix484.
PubMed 29126292
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Immunogenicity of V212 in Adult Patients With Autoimmune Disease
- ClinicalTrials.gov ID
- NCT01527383
- Acronym / sponsor ID
- V212-009
- Conditions
- Herpes Zoster
- Keywords
- Shingles
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 354 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 21 Feb 2012 (actual)
- Primary completion
- 26 Feb 2013 (actual)
- Study completion
- 26 Feb 2013 (actual)
- First posted
- 7 Feb 2012 (estimated)
- Results
- Posted 14 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to evaluate the safety and immunogenicity of V212 vaccine in adults with autoimmune disease, including participants with rheumatoid arthritis, psoriatic arthritis, psoriasis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, and other similar diseases. The primary hypothesis is that vaccination with V212 vaccine will elicit significant VZV-specific immune responses at approximately 28 days after vaccination 4. The statistical criterion for significance requires that the lower bound of the 2-sided 95% confidence interval of the geometric mean fold rise in vaccine recipients is >1.0.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| V212 | Experimental | Biological: V212Participants receive V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
| Placebo | Placebo comparator | Biological: PlaceboParticipants receive placebo as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosed with an autoimmune disease
- Clinically stable disease for at least 30 days before enrollment
- Not likely to undergo hematopoietic stem cell transplantation during the study period
- Receiving at least one parenteral or oral biologic agent, such as a Tumor Necrosis factor (TNF) alpha inhibitor, or a parenteral or oral non-biologic therapy, at a stable dose for at least 3 months, with no planned or anticipated changes
- History of varicella, antibodies to VZV, or residence for at least 30 years in a country with endemic VZV infection, or if participant is less than 30 years old, attended primary or secondary school in a country with endemic VZV infection
Key exclusion criteria (5 listed)
- Prior history of Herpes Zoster (shingles) within 1 year before enrollment
- Prior varicella or zoster vaccine
- Active central nervous system lupus erythematosus requiring therapeutic intervention within 90 days of enrollment
- Prior or planned therapy containing rituximab or other anti-Cluster of Differentiation (CD) 20 monoclonal antibodies from 3 months before enrollment through 28 days postdose 4
- Systemic corticosteroid therapy, prednisone, or equivalent over 40 mg daily at the time of enrollment
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 |
|---|---|---|
| V212Also: Inactivated Varicella-Zoster (VZV) vaccineV212 viral antigen for HZ | Biological | V212 |
| PlaceboPlacebo comparator to V212 vaccine | Biological | Placebo |
Primary outcome
Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA)
Time frame: Baseline and ~28 days after Vaccination 4 (~Day 118)
Serum samples were tested for antibody response using a gpELISA. The GMFR is response at approximately 28 days postdose 4 / response predose on Day 1.
GMFR in VZV Antibody Response Measured by VZV Interferon-gamma (IFN-g) Enzyme-linked Immunospot (ELISPOT) Assay
Time frame: Baseline and ~28 days after Vaccination 4 (~Day 118)
Serum samples were tested for activity using a VZV ELISPOT assay. The assay detects IFN-γ-secreting, VZV-specific cells from peripheral blood mononuclear cells (PBMCs). The unit of measure of the assay is ELISPOT cell count / 10^6 PBMCs, and is expressed as geometric mean count (GMC). The GMFR is GMC at ~28 days after Vaccination 4 / GMC predose on Day 1.
Percentage of Participants With a Serious Adverse Event
Time frame: Up to ~28 days after Vaccination 4 (~Day 118)
A serious adverse event (SAE) is defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants with one or more SAE was assessed.
3 secondary outcomes
Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card
Time frame: Up to Day 5 after any vaccination
Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card
Time frame: Up to ~28 days after Vaccination 4 (~Day 118)
Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card
Time frame: Up to ~28 days after Vaccination 4 (~Day 118)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29126292Eberhardson M, Hall S, Papp KA, Sterling TM, Stek JE, Pang L, Zhao Y, Parrino J, Popmihajlov Z. Safety and Immunogenicity of Inactivated Varicella-Zoster Virus Vaccine in Adults With Autoimmune Disease: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Clin Infect Dis. 2017 Oct 1;65(7):1174-1182. doi: 10.1093/cid/cix484.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing V212 in people with Herpes Zoster, run by Merck Sharp & Dohme LLC.
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 5 inclusion and 5 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 14 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 14 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) (time frame: Baseline and ~28 days after Vaccination 4 (~Day 118)). The study lists 3 primary outcomes in all. 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 NCT01527383, 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 14 Jan 2019.