Safety and Effectiveness of Live Zoster Vaccine in Anti-Tumor Necrosis Factor (TNF) Users (VERVE Trial)

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT02538341
• Collaborator: Oregon Health and Science University (Other)
• Enrollment: 617
• Locations: 34
• Arms: 2
• Actual Duration (Months): 55
• Patients Per Site: 18.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The VaricElla zosteR VaccinE (VERVE) trial evaluates the safety and effectiveness of the Herpes zoster (HZ) vaccine for shingles, Zostavax, in patients over 50 years old with arthritis and other diseases who are using anti-tumor necrosis factor (TNF) therapy and who have not previously received the vaccine.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis; Inflammatory Arthritis; Arthritis; Psoriatic Arthritis; Psoriasis; Ankylosing Spondylitis; Enteropathic Arthritis; Crohn's Disease	Biological: Herpes Zoster (HZ) Vaccine; Drug: Placebo	Phase 2

Detailed Description

Herpes zoster (HZ), also known as "shingles", is caused by reactivation and multiplication of the ubiquitous varicella zoster virus (VZV) that remains latent in everyone's sensory neurons following varicella, or "chickenpox". Among individuals who live to age 85, the lifetime risk for herpes zoster (HZ) is 50%, and more than one in five individuals affected by zoster develop post-herpetic neuralgia, resulting in chronic pain. Other serious complications include encephalitis, permanent vision loss, or more rarely, dissemination and death. Fortunately, a live attenuated vaccine is available and can reduce herpes zoster (HZ) risk by up to 70%. For patients with rheumatoid arthritis (RA), this vaccine has great potential to provide improved quality of life by reducing the incidence and complications associated with zoster. Due to the underlying disease and/or treatments (e.g. steroids) for rheumatoid arthritis (RA), the risk of herpes zoster (HZ) in rheumatoid arthritis patients is approximately double in the general population. This increased risk should make prevention of zoster and vaccination exceedingly important for rheumatoid arthritis patients. In fact, because of a higher overall absolute risk for herpes zoster (HZ) in rheumatoid arthritis, the vaccine yields a comparable or even greater absolute risk reduction to reduce the risk of shingles and post-herpetic neuralgia in a rheumatoid arthritis population as it does in the general population. However, the use of the herpes zoster (HZ) in rheumatoid arthritis, patients is very low (< 5%), and less frequently used than for the general population.

National guidelines from the Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) recommend a single dose of the herpes zoster (HZ) vaccine for all individuals age 60 or older, with the vaccine more recently gaining Federal Drug Administration (FDA) -approval for administration to persons age 50 and older. While a large number of rheumatoid arthritis patients would otherwise be recommended to receive this vaccine on the basis of age, theoretical safety concerns related to vaccination likely explain the very low vaccination rates observed. Currently, the Federal Drug Administration (FDA), the Advisory Committee on Immunization Practices (ACIP), and the American College of Rheumatology (ACR) consider the live zoster vaccine contraindicated in patients receiving immunosuppressive medications, such as biologic therapies. Such contraindication stems from the theoretical safety concern that these individuals could develop a varicella-like infection from the vaccine virus strain. However, investigators hypothesize that this vaccine can safely be given in this setting, as no published data is available to suggest that these safety concerns are warranted. A growing body of observational data suggests that vaccinating rheumatoid arthritis patients receiving biologic therapies with this vaccine may in fact be safe. Moreover, and similarly with little or no evidence, the Advisory Committee on Immunization Practices (ACIP) considers the vaccine safe and acceptable for patients using methotrexate at doses commonly used to treat rheumatoid arthritis (e.g. <= 25mg/week) and for patients using glucocorticoids at prednisone-equivalent doses of ≤ 20 mg/day.

In light of 1) a substantial elevated herpes zoster (HZ) risk among rheumatoid arthritis patients; 2) national data showing most rheumatoid arthritis patients are not vaccinated for herpes zoster (HZ) ; and 3) the high effectiveness of this vaccine in the general population, the investigators propose to conduct the Varicella zostER VaccinE (VERVE) trial, a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and long-term effectiveness of the live herpes zoster (HZ) vaccine. This study will recruit 1,000 individuals age 50 years or older currently receiving anti-tumor necrosis factor (TNF) therapy for rheumatoid arthritis or other diseases. Within a relevant 6-week safety window, the investigators will collect serious adverse events (satisfying a regulatory definition of a Serious Adverse Event) including non-serious events of vaccine-strain varicella-like infection or herpes zoster (HZ). Beyond the key public health importance of the clinical question addressed, clinical trial methodological innovations anticipated for this unique large pragmatic trial. Additionally, the investigators will study vaccine tolerability and long-term effectiveness through a linkage to health plan data to allow for cost-effective follow-up while minimizing participant and study-site burden. Results from this study will facilitate the parent trial and change rheumatoid arthritis management by demonstrating the clinical safety and immunogenicity of the live zoster vaccine among current anti-tumor necrosis factor (TNF) users. Rheumatologists and other providers will be able to improve the care, outcomes, and quality of life for patients using anti-tumor necrosis factor (TNF) therapy, substantially decreasing the morbidity of herpes zoster and its complications over a lifetime.

Study Design

• Study Type: Interventional
• Actual Enrollment: 617 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety and Effectiveness of Live Zoster Vaccine in Anti-TNF Users (VERVE Trial)
• Actual Study Start Date: May 1, 2016
• Actual Primary Completion Date: Dec 1, 2019
• Actual Study Completion Date: Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Zostavax (Zoster Vaccine Live) Zostavax (zoster vaccine live) is used to prevent herpes zoster (HZ) virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active herpes zoster (HZ) vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm.	Biological: Herpes Zoster (HZ) Vaccine; Other Names: Zostavax
Placebo Comparator: Placebo Normal Saline Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm.	Drug: Placebo; Other Names: Normal Saline

Outcome Measures

Primary Outcome Measures

1. GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Immunoglobulin G (IgG) Levels From Baseline at 6 Weeks [6 weeks post vaccination]

   Study protocol defined measure for immunogenicity samples.

2. GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Enzyme-linked Immune Absorbent Spot (ELISpot) Interferon Gamma (IFNg) Levels From Baseline at 6 Weeks [6 weeks post vaccination]

   Study protocol defined measure for immunogenicity samples.

Secondary Outcome Measures

1. GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Immunoglobulin G (IgG) Levels From Baseline at 1 Year [Baseline to 1 year]

   Study defined measure from labs. GMFR (Geometric Mean Fold Rise ) in varicella zoster virus (VZV) glycoprotein enzyme-linked immunosorbent assay (gpELISA) immunoglobulin G (IgG) levels

2. GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Enzyme-linked Immune Absorbent Spot (ELISpot) Interferon Gamma (IFNg) Levels From Baseline at 1 Year [Baseline to 1 year]

   Study defined measures from labs. GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) enzyme-linked immune absorbent spot (ELISpot) interferon gamma (IFNg)

3. Number of Samples With Confirmed Varicella ["Placebo Normal Saline Arm/Group was assessed up to 6 months and the "Zoster Vaccine Live (Zostavax)" Arm/Group was assessed up to 1 year]

   Evaluated all serious adverse events (SAEs) AND non-serious varicella zoster virus (VZV) events

4. Vaccine Tolerability Within 42 Days Following Vaccination. [42 days post vaccination]

   Patient self report data in the form of a diary to include injection site reactions; symptoms of swelling, redness or tenderness. Diary was completed from study injection administration up to 6 week visit

5. Evaluate Rheumatoid Arthritis Disease Activity Using the Clinical Disease Activity Index (CDAI) [42 days post vaccination]

   Rheumatoid arthritis disease activity will be measured using the clinical disease activity index (CDAI). Clinical disease activity index (CDAI) is a measure of rheumatoid arthritis disease activity and is scored on a scale ranging from 0-76, with lower numbers indicated better control of disease. Values <=10 are consistent with low disease activity or remission.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must be 50 years of age or older

• Must be currently treated with an anti-tumor necrosis factor (TNF) therapy** at the time of study drug administration, allowing for small deviations in dosing frequency and logistic feasibility (e.g. study visits to occur on a week day). Date of previous dose of medication is required. Specifically, meets one of the following: Etanercept dose within 9 days (1 week + 2 days), Adalimumab dose within 16 days (2 weeks + 2 days), Certolizumab Subcutaneous (SC) dose within 16 to 32 days depending on frequency schedule (2 weeks + 2 days, or 4 weeks and 4 days), Golimumab Subcutaneous (SC) dose within 32 days (4 weeks + 4 days), Golimumab Intravenous (IV) dose within 64 days (9 weeks + 1 day), Infliximab IV dose within last 64 days (9 weeks + 1 day)

**any form of biosimilar for the above listed anti-tumor necrosis factor (TNF) medications is acceptable

• Diagnosis of rheumatoid arthritis or another inflammatory arthritis (Phase 1A); or other inflammatory condition (e.g. psoriasis) requiring use of anti-tumor necrosis factor (TNF) therapy (Phase 1B and II)

• Phase I subjects must test positive for varicella-zoster virus (VZV) antibody immunoglobulin G (IgG)

• Subjects should have a self-reported history of prior varicella infection (i.e. chicken pox) or long-term residence (>30 years) in the continental United States.

• Phase IA subjects must not have received any oral or systemic glucocorticoids within 30 days prior to vaccination. Intra-articular glucocorticoid injections and inhaled glucocorticoids within the previous 30 days are acceptable.

• Subjects should be on stable doses of all biologic and non-biologic Disease-modifying antirheumatic drugs (DMARDs) for a minimum of 30 days prior to vaccination.

• Eligible women must be post-menopausal (> 1 year since last menstrual period) or have a surgical history of bilateral oophorectomy or hysterectomy.

• Subjects should be ambulatory, community dwelling and capable of giving informed consent.

Exclusion Criteria:

• Documented varicella-zoster virus (VZV) antibody immunoglobulin G (IgG) negative result

• Prior use of the zoster vaccine (Zostavax®, Merck)

• Glucocorticoids at a prednisone-equivalent daily dose > 10mg/day (for Phase 1B and Phase II participants; all systemic glucocorticoid use is prohibited for Phase 1A patients)

• Any known contraindication to Zostavax® vaccine, including allergy or sensitivity to gelatin or any other vaccine component

• Known human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)

• Currently receiving radiation or chemotherapy for any type of malignancy

• Any current use (within the last 30 days) of acyclovir, valacyclovir, famciclovir, or foscarnet

• Receipt of any other immunizations within one month before study vaccination (2 weeks in the case of inactivated influenza vaccines or other non-replicating immunization products [e.g., diphtheria-tetanus (dT), pneumococcal vaccine, hepatitis A vaccine, hepatitis B vaccine]), or scheduled within 6 weeks after recruitment.

• Active infection or inter-current illness (e.g., urinary tract infection, influenza)

• Participated in an investigational study within 1 month prior to study entry

• Active drug or alcohol use, dependence, or any other reason that, in the opinion of the site investigator, would interfere with the study

• Significant underlying illness that would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to less than 3 years)

• Any other reason that, in the opinion of the site investigator, would interfere with required study related evaluations (e.g. uncontrolled comorbidity, life expectancy < 1 year)

• Patients who have household contact with varicella-susceptible pregnant women or severely immunosuppressed individuals without history of primary varicella.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rheumatology Associates, PC	Birmingham	Alabama	United States	35205
2	Total Skin and Beauty Dermatology Center, PC	Birmingham	Alabama	United States	35205
3	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
4	Rheumatology Associates of North Alabama, PC	Huntsville	Alabama	United States	35801
5	Clinical and Translational Research Center of Alabama, PC	Tuscaloosa	Alabama	United States	35406
6	SunValley Arthritis Center, Ltd	Peoria	Arizona	United States	85381
7	Arthritis Association of Southern California	Los Angeles	California	United States	90015
8	The Regents of the University of California Los Angeles	Los Angeles	California	United States	90095
9	Rheumatology Consultants of Delaware dba Delaware Arthritis	Lewes	Delaware	United States	19958
10	Center for Arthritis and Rheumatic Diseases	Miami	Florida	United States	33157
11	Coral Research Clinic Corp	Miami	Florida	United States	33175
12	Arthritis Research of Florida, Inc	Palm Harbor	Florida	United States	34684
13	Sarasota Arthritis Research Center	Sarasota	Florida	United States	34239
14	West Broward Rheumatology Associates, Inc	Tamarac	Florida	United States	33321
15	North Georgia Rheumatology Group	Lawrenceville	Georgia	United States	30046
16	Arthritis Research Center Foundation, NDB	Wichita	Kansas	United States	67214
17	Ochsner Clinic Baton Rouge	Baton Rouge	Louisiana	United States	70809
18	Ochsner Clinic Foundation, New Orleans	New Orleans	Louisiana	United States	70121
19	Rheumatology & Osteoporosis Specialists	Shreveport	Louisiana	United States	71101
20	Boston Medical Center	Boston	Massachusetts	United States	02118
21	Pine Hollow Partners	East Lansing	Michigan	United States	48823
22	St. Paul Rheumatology	Eagan	Minnesota	United States	55121
23	University of Nebraska Medical Center	Omaha	Nebraska	United States	68106
24	The Center for Rheumatology, LLP	Albany	New York	United States	12293
25	Mary Imogene Bassett Hospital, Bassett Research Institute	Cooperstown	New York	United States	13326
26	The Ohio State University	Columbus	Ohio	United States	43203
27	Oregon Health & Science University	Portland	Oregon	United States	97239
28	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
29	Carolina Health Specialists	Myrtle Beach	South Carolina	United States	29572
30	Arthritis Associates, PLLC	Hixson	Tennessee	United States	37343
31	West Tennessee Research Institute	Jackson	Tennessee	United States	38305
32	Southwest Rheumatology Research, LLC	Mesquite	Texas	United States	75150
33	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
34	West Virginia Research Institute, PLLC	South Charleston	West Virginia	United States	25309

Sponsors and Collaborators

• University of Alabama at Birmingham
• Oregon Health and Science University

Investigators

• Principal Investigator: Jeffrey R Curtis, MD, MS, MPH, University of Alabama at Birmingham

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 8, 2020

More Information

Publications

None provided.

• Responsible Party: Jeff Curtis, MD, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02538341
• Other Study ID Numbers: VERVE-UM1; NCT01967316; NCT02538757
• First Posted: Sep 2, 2015
• Last Update Posted: Nov 23, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Spondylitis; Arthritis; Arthritis, Psoriatic; Spondylitis, Ankylosing; Crohn Disease; Psoriasis

Study Results

Participant Flow

Arm/Group Title	Zoster Vaccine Live (Zostavax)	Placebo Normal Saline
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine	Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Placebo
Period Title: Overall Study
STARTED	310	307
Week 6 (Primary Outcome)	303	299
Month 6 (Safety Outcome)	276	260
1 Year Visit	254	0
COMPLETED	254	260
NOT COMPLETED	56	47

Baseline Characteristics

Arm/Group Title	Zoster Vaccine Live (Zostavax)	Placebo Normal Saline	Total
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine	Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Placebo	Total of all reporting groups
Overall Participants	310	307	617
Age, Customized (years) [Mean (Standard Deviation) ]
Age	62.7 (7.6)	63.1 (7.4)	62.9 (7.5)
Age, Customized (Count of Participants)
50-59	126 40.6%	102 33.2%	228 37%
60-69	125 40.3%	142 46.3%	267 43.3%
70-79	50 16.1%	55 17.9%	105 17%
80-89	9 2.9%	7 2.3%	16 2.6%
90-99	0 0%	1 0.3%	1 0.2%
Sex: Female, Male (Count of Participants)
Female	207 66.8%	201 65.5%	408 66.1%
Male	103 33.2%	106 34.5%	209 33.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.6%	1 0.3%	3 0.5%
Asian	0 0%	1 0.3%	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	24 7.7%	14 4.6%	38 6.2%
White	202 65.2%	197 64.2%	399 64.7%
More than one race	1 0.3%	3 1%	4 0.6%
Unknown or Not Reported	81 26.1%	91 29.6%	172 27.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	14 4.5%	12 3.9%	26 4.2%
Not Hispanic	208 67.1%	194 63.2%	402 65.2%
Other Ethnicity	7 2.3%	7 2.3%	14 2.3%
Unknown/ Not reported	81 26.1%	94 30.6%	175 28.4%
Region of Enrollment (participants) [Number]
United States	310 100%	307 100%	617 100%

Outcome Measures

1. Primary Outcome

Title	GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Immunoglobulin G (IgG) Levels From Baseline at 6 Weeks
Description	Study protocol defined measure for immunogenicity samples.
Time Frame	6 weeks post vaccination

Outcome Measure Data

Analysis Population Description

Zoster vaccine live arm 7 did not complete Week 6; 5 lost to follow-up, 2 withdrew consent. Placebo arm 8 did not complete Week 6; 5 lost to follow-up, 3 withdrew consent. Zoster vaccine live arm 300 immunogenicity samples collected, 294 useable immunoglobulin G (IgG) samples, 287 usable immunoglobulin G (IgG) sample pairs. For the placebo arm 298 immunogenicity samples collected, 289 useable immunoglobulin G (IgG) samples, 259 usable immunoglobulin G (IgG) sample pairs.

Arm/Group Title	Zoster Vaccine Live (Zostavax)	Placebo Normal Saline
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine	Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Placebo
Measure Participants	303	299
Measure IgG samples pairs	287	289
Geometric Mean (95% Confidence Interval) [GMFR (Geometric Mean Fold Rise )]	1.33	1.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zoster Vaccine Live (Zostavax), Placebo Normal Saline
	Comments	Study protocol defined measure for immunogenicity samples. Participants must have at least 1 post vaccine immunogenicity measure to determine the GMFR (a priori analysis)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments	p values, from a generalized linear model on the rank order of the week 6 - baseline change using normal distribution and reciprocal link.
	Method	a generalized linear model
	Comments	p value,from a generalized linear model on the rank order of the week 6 - baseline change using normal distribution and reciprocal link.

2. Primary Outcome

Title	GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Enzyme-linked Immune Absorbent Spot (ELISpot) Interferon Gamma (IFNg) Levels From Baseline at 6 Weeks
Description	Study protocol defined measure for immunogenicity samples.
Time Frame	6 weeks post vaccination

Outcome Measure Data

Analysis Population Description

Zoster vaccine live arm 7 did not complete Week 6; 5 lost to follow-up, 2 withdrew consent. Placebo arm 8 did not complete Week 6; 5 lost to follow-up, 3 withdrew consent. For the zoster vaccine live arm 300 immunogenicity samples collected, 290 useable interferon gamma (IFNg) samples, 259 usable interferon gamma (IFNg) sample pairs. For the placebo arm 298 immunogenicity samples collected, 289 useable interferon gamma (IFNg) samples, 275 usable interferon gamma (IFNg)sample pairs.

Arm/Group Title	Zoster Vaccine Live (Zostavax)	Placebo Normal Saline
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine	Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Placebo
Measure Participants	303	299
Measure lab samples pairs	259	275
Geometric Mean (95% Confidence Interval) [GMFR (Geometric Mean Fold Rise )]	1.39	1.15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zoster Vaccine Live (Zostavax), Placebo Normal Saline
	Comments	Study protocol defined measure for immunogenicity samples. Participants must have at least 1 post vaccine immunogenicity measure to determine the GMFR (a priori analysis)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments	p values, from a generalized linear model on the rank order of the week 6 - baseline change using normal distribution and reciprocal link.
	Method	a generalized linear model
	Comments	p values, from a generalized linear model on the rank order of the week 6 - baseline change using normal distribution and reciprocal link.

3. Secondary Outcome

Title	GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Immunoglobulin G (IgG) Levels From Baseline at 1 Year
Description	Study defined measure from labs. GMFR (Geometric Mean Fold Rise ) in varicella zoster virus (VZV) glycoprotein enzyme-linked immunosorbent assay (gpELISA) immunoglobulin G (IgG) levels
Time Frame	Baseline to 1 year

Outcome Measure Data

Analysis Population Description

Zoster vaccine live arm 56 did not complete Year 1; 51 lost to follow-up, 3 withdrew consent, 2 deaths prior to month 6. Vaccine arm only. Placebo arm not applicable for this exploratory outcome. For the zoster vaccine live arm 131 immunogenicity samples collected, 122 useable immunoglobulin G (IgG) samples, 114 usable immunoglobulin G (IgG) sample pairs.

Arm/Group Title	Zoster Vaccine Live (Zostavax)
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine
Measure Participants	254
Measure lab samples	114
≤ Baseline	41
Within 20%	6
> 20%	67

4. Secondary Outcome

Title	GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Enzyme-linked Immune Absorbent Spot (ELISpot) Interferon Gamma (IFNg) Levels From Baseline at 1 Year
Description	Study defined measures from labs. GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) enzyme-linked immune absorbent spot (ELISpot) interferon gamma (IFNg)
Time Frame	Baseline to 1 year

Outcome Measure Data

Analysis Population Description

Zoster vaccine live arm 56 did not complete Year 1; 51 lost to follow-up, 3 withdrew consent, 2 deaths prior to month 6. Vaccine arm only. Placebo arm not applicable. For the zoster vaccine live arm 131 immunogenicity samples collected, 125 useable interferon gamma (IFNg) samples, 116 usable interferon gamma (IFNg) sample pairs.

Arm/Group Title	Zoster Vaccine Live (Zostavax)
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine
Measure Participants	254
Measure lab samples	116
≤ Baseline	87
Within 20%	2
> 20%	27

5. Secondary Outcome

Title	Number of Samples With Confirmed Varicella
Description	Evaluated all serious adverse events (SAEs) AND non-serious varicella zoster virus (VZV) events
Time Frame	"Placebo Normal Saline Arm/Group was assessed up to 6 months and the "Zoster Vaccine Live (Zostavax)" Arm/Group was assessed up to 1 year

Outcome Measure Data

Analysis Population Description

Lab samples collected for testing for varicella

Arm/Group Title	Zoster Vaccine Live (Zostavax)	Placebo Normal Saline
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine	Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Placebo
Measure Participants	310	307
Measure lab sample	4	4
Total Samples Tested	4	4
Total Sample with Confirmed Varicella	0	0

6. Secondary Outcome

Title	Vaccine Tolerability Within 42 Days Following Vaccination.
Description	Patient self report data in the form of a diary to include injection site reactions; symptoms of swelling, redness or tenderness. Diary was completed from study injection administration up to 6 week visit
Time Frame	42 days post vaccination

Outcome Measure Data

Analysis Population Description

7 participants from the Zostavax arm and 8 participants from the placebo arm did not complete 6 week visit for various a reasons (e.g., lost to follow up, consent withdrawn , etc.)

Arm/Group Title	Zoster Vaccine Live (Zostavax)	Placebo Normal Saline
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine	Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Placebo
Measure Participants	303	299
Count of Participants [Participants]	60 19.4%	13 4.2%

7. Secondary Outcome

Title	Evaluate Rheumatoid Arthritis Disease Activity Using the Clinical Disease Activity Index (CDAI)
Description	Rheumatoid arthritis disease activity will be measured using the clinical disease activity index (CDAI). Clinical disease activity index (CDAI) is a measure of rheumatoid arthritis disease activity and is scored on a scale ranging from 0-76, with lower numbers indicated better control of disease. Values <=10 are consistent with low disease activity or remission.
Time Frame	42 days post vaccination

Outcome Measure Data

Analysis Population Description

120 participants on Zostavax arm and 129 participants on placebo arms were non-rheumatoid arthritis participants.

Arm/Group Title	Zoster Vaccine Live (Zostavax)	Placebo Normal Saline
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine	Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Placebo
Measure Participants	190	178
CDAI at Baseline	9.54 (10.6)	9.34 (9.77)
CDAI at week 6	10.48 (10.93)	10.31 (10.87)
Changes in CDAI	0.77 (7.33)	0.98 (8.55)

Adverse Events

Time Frame	Adverse events and serious adverse events (SAEs) within 42 days of vaccination (placebo and vaccine). 6 months (final safety assessment for placebo arm).Serious Adverse Events (SAEs) up to 1 year (final safety assessment for treatment arm).
Adverse Event Reporting Description	Serious adverse events (SAEs) AND non-serious varicella zoster virus events. SAEs will include all that satisfy the FDA-accepted definition of SAEs (results in death, life threatening, results in or prolongs hospitalization, and any Herpes Zoster event). Adverse events (non-serious) include rashes,blisters,fever of greater than 101,sickness/illness. Also, any redness, swelling, tenderness of the injection site or any other body part.
Arm/Group Title	Zoster Vaccine Live (Zostavax)		Placebo Normal Saline
Arm/Group Description	Zostavax (zoster vaccine live) is used to prevent herpes zoster virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active Herpes Zoster Vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Herpes Zoster Vaccine		Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm. Placebo
All Cause Mortality
	Zoster Vaccine Live (Zostavax)		Placebo Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/310 (1%)		0/307 (0%)
Serious Adverse Events
	Zoster Vaccine Live (Zostavax)		Placebo Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/310 (3.2%)		8/307 (2.6%)
Cardiac disorders
Chest pain	0/310 (0%)	0	1/307 (0.3%)	1
Congenital, familial and genetic disorders
Death	3/310 (1%)	3	0/307 (0%)	0
Gastrointestinal disorders
Blocked Bowel	3/310 (1%)	3	0/307 (0%)	0
Infections and infestations
Respiratory Syncytial Virus Pneumonia	0/310 (0%)	0	1/307 (0.3%)	1
Sepsis due to pyelonephritis	0/310 (0%)	0	1/307 (0.3%)	1
Injury, poisoning and procedural complications
Hip fracture	0/310 (0%)	0	1/307 (0.3%)	2
Hip Fracture	1/310 (0.3%)	1	0/307 (0%)	0
Musculoskeletal and connective tissue disorders
Right groin pain secondary to edema of the right hip adductor	1/310 (0.3%)	1	0/307 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ductal carcinoma	1/310 (0.3%)	1	0/307 (0%)	0
Nervous system disorders
Pseudoseizures	1/310 (0.3%)	1	0/307 (0%)	0
Syncope and collapse	0/310 (0%)	0	1/307 (0.3%)	1
Renal and urinary disorders
Kidney stone	1/310 (0.3%)	1	0/307 (0%)	0
Left Ureteral Obstruction	1/310 (0.3%)	1	0/307 (0%)	0
Pyelonephritis	0/310 (0%)	0	1/307 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/310 (0%)	0	1/307 (0.3%)	1
Vascular disorders
Elevated blood pressure	0/310 (0%)	0	1/307 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Zoster Vaccine Live (Zostavax)		Placebo Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	120/310 (38.7%)		75/307 (24.4%)
Blood and lymphatic system disorders
Anemia	1/310 (0.3%)	1	0/307 (0%)	0
Low Blood Sugar	0/310 (0%)	0	1/307 (0.3%)	1
Cardiac disorders
Heart Irregularities	0/310 (0%)	0	1/307 (0.3%)	1
Eye disorders
Eye pain/Redness	2/310 (0.6%)	2	1/307 (0.3%)	1
Gastrointestinal disorders
Diarrhea	0/310 (0%)	0	1/307 (0.3%)	1
Anaphylaxis	0/310 (0%)	0	1/307 (0.3%)	1
Nausea	4/310 (1.3%)	6	1/307 (0.3%)	2
Constipation	1/310 (0.3%)	1	0/307 (0%)	0
General disorders
Back pain	1/310 (0.3%)	1	0/307 (0%)	0
Fever, Flu like Symptom	9/310 (2.9%)	10	8/307 (2.6%)	12
Cold	0/310 (0%)	0	1/307 (0.3%)	1
Dizziness	1/310 (0.3%)	1	1/307 (0.3%)	1
Headache , Migraine	2/310 (0.6%)	2	3/307 (1%)	3
Sore Throat	0/310 (0%)	0	1/307 (0.3%)	1
Cyst	1/310 (0.3%)	1	0/307 (0%)	0
Cat Bite	1/310 (0.3%)	1	0/307 (0%)	0
Canker sore	0/310 (0%)	0	1/307 (0.3%)	1
hidradenitis	0/310 (0%)	0	1/307 (0.3%)	1
Lower Extremity Pain	0/310 (0%)	0	1/307 (0.3%)	1
Law Pain	0/310 (0%)	0	1/307 (0.3%)	1
Not Specifies	20/310 (6.5%)	24	7/307 (2.3%)	9
Infections and infestations
Infection	8/310 (2.6%)	15	9/307 (2.9%)	18
Bursitis	0/310 (0%)	0	1/307 (0.3%)	1
Injury, poisoning and procedural complications
Ankle Sprain	0/310 (0%)	0	1/307 (0.3%)	1
Foot and Groin Injury	1/310 (0.3%)	1	1/307 (0.3%)	1
Fracture	1/310 (0.3%)	1	0/307 (0%)	0
Ruptured vericose vein	0/310 (0%)	0	1/307 (0.3%)	1
Sprained ankle	0/310 (0%)	0	1/307 (0.3%)	1
Musculoskeletal and connective tissue disorders
Joint Pain	1/310 (0.3%)	1	0/307 (0%)	0
Arthritis pain	1/310 (0.3%)	1	1/307 (0.3%)	1
Edema	0/310 (0%)	0	1/307 (0.3%)	1
Renal and urinary disorders
Angiomyolipoma	0/310 (0%)	0	1/307 (0.3%)	1
Skin and subcutaneous tissue disorders
Rash	14/310 (4.5%)	14	11/307 (3.6%)	14
Injection Site Reaction	47/310 (15.2%)	61	7/307 (2.3%)	13
Blister	0/310 (0%)	0	2/307 (0.7%)	2
Burn	0/310 (0%)	0	1/307 (0.3%)	1
Bug Bites	0/310 (0%)	0	1/307 (0.3%)	1
Psoriasis Flare	2/310 (0.6%)	2	2/307 (0.7%)	2
Chelitis	1/310 (0.3%)	1	0/307 (0%)	0
Poison Ivy	0/310 (0%)	0	1/307 (0.3%)	1
Herpes sore	1/310 (0.3%)	1	0/307 (0%)	0
Hives	0/310 (0%)	0	1/307 (0.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.