Herpes Zoster Clinical Trial
Official title:
CSP #403 - Trial of Varicella Zoster Vaccine for the Prevention of Herpes Zoster and Its Complications
The incidence and severity of HZ (or shingles), as well as the frequency and severity of its
complications, increases markedly with increasing age. More than half of all cases occur in
persons over the age of 60. Even without complications, HZ can interfere with an elderly
patient's ability to perform essential activities of daily living, resulting in a loss of
independence that is emotionally devastating and frequently irreversible. The most common
complication of HZ in elderly persons is postherpetic neuralgia (PHN), which frequently
results in disordered sleep, chronic fatigue, anxiety and severe depression. Antiviral
therapy has a modest impact on the acute phase of HZ. However, it does not appear to prevent
the development of PHN.
This study is a 5.5 year randomized, double-blind, placebo-controlled, efficacy trial to
determine whether vaccination with live-attenuated Oka/Merck varicella-zoster decreases the
incidence and/or severity of herpes zoster (HZ) and its complications in adults 60 years of
age and older.
Primary Hypothesis:
Immunization with live, attenuated (Oka/Merck) varicella-zoster vaccine will significantly
reduce the burden of illness associated with herpes zoster (HZ).
Secondary Hypotheses:
Immunization with live, attenuated (Oka/Merck) varicella-zoster vaccine will reduce the
incidence of postherpetic neuralgia (PHN).
Primary Outcomes:
The primary outcome is the burden of illness due to HZ defined by the area under the worst
pain versus time curve measured during the 6 month period following HZ rash onset in
subjects who develop of HZ. The burden of illness outcome is sensitive to the incidence,
severity, and duration of HZ-associated pain. The secondary outcome is the incidence of PHN,
where PHN is defined as HZ-associated pain rated as greater than or equal to 3 (on a 0 to 10
scale) persisting or appearing more than 30 days after the onset of the HZ rash.
Interventions:
Immunization with 0.5 ml, live, attenuated (Oka/Merck) varicella-zoster vaccine versus
vaccine placebo.
Study Abstract:
The incidence and severity of HZ (or shingles), as well as the frequency and severity of its
complications, increases markedly with increasing age. More than half of all cases occur in
persons over the age of 60. Even without complications, HZ can interfere with an elderly
patient's ability to perform essential activities of daily living, resulting in a loss of
independence that is emotionally devastating and frequently irreversible. The most common
complication of HZ in elderly persons is postherpetic neuralgia (PHN), which frequently
results in disordered sleep, chronic fatigue, anxiety and severe depression. Antiviral
therapy has a modest impact on the acute phase of HZ. However, it does not appear to prevent
the development of PHN.
This study was a 5.5 year randomized, double-blind, placebo-controlled, efficacy trial to
determine whether vaccination with live-attenuated Oka/Merck varicella-zoster decreases the
incidence and/or severity of herpes zoster (HZ) and its complications in adults 60 years of
age and older; 37,200 subjects over 60 years of age will be randomized at 22 sites to
receive either vaccine or placebo. At least one third of the subjects were to be 70 years of
age or older. Subjects were followed actively for HZ until at least 750 cases of HZ and at
least 62 cases of PHN occurred. Subjects who developed HZ were evaluated for severity and
duration of associated pain, extent and duration of rash, and for changes in quality of life
associated with the disease for six months after the onset of HZ rash. All adverse events
(serious and non-serious) occurring within 42 days after vaccination were recorded.
Thereafter, serious adverse events were recorded if assessed as possibly related to the
vaccination. An adverse event substudy was to enroll 6000 subjects for recording all adverse
events on a vaccination Report Card. Substudy participants were also followed for any
hospital admissions during the study.
The study was initiated in December 1998. Patient recruitment began in November 1998 at one
site, at 20 sites between February 1999 and July 1999, and at one site that was added in
January 2000. On September 26, 2001, enrollment in the study was completed with 38,456
randomized subjects. The time point for the study definition of PHN was changed by protocol
amendment from 30 days to 90 days after HZ rash onset. A formal sample size re-estimation
was performed in June 2003. The Executive Committee and DSMB reviewed these results and
approved the increase in event size from 400 to 750 evaluable cases of HZ for the primary
endpoint. It was projected that the number of evaluable cases of HZ for the primary endpoint
and the number of evaluable cases of PHN for the secondary (co-primary) endpoint would be
observed by the end of September 2003. Therefore, the Study initiated its closeout plan
beginning in October 2004. Follow-up of the last suspected case of HZ was completed in March
2004 and closeout interviews for the more than 37,000 surviving subjects were completed as
of April 28, 2004.
The results of the main efficacy and safety analyses were unblinded on December 1, 2004, and
presented to the DSMB, Executive Committee, and representatives for Merck & Co., Inc.
Letters were sent to the study subjects informing them of the overall results and the
treatment they received. The main manuscript was published in the New England Journal of
Medicine (June 2005; 352:2271-84). The vaccine was approved for the prevention of shingles
by the FDA on May 25, 2006. The main efficacy study is closed. Additionally, three
substudies have been conducted:
A substudy (CSP#403B) was initiated in November 2005 to offer investigational zoster vaccine
to the placebo recipients of CSP#403. Vaccination was completed in March 2007 with 13,681
(75%) of the placebo recipients vaccinated. This substudy is closed. The safety results from
the substudy were published in the Journal of Infectious Diseases (J Infect Dis. 2013 May 31
epub).
A short-term persistence substudy (CSP#403A) was initiated in September 2004 to extend the
follow-up vaccine and placebo recipients to assess the longer term effectiveness of the
vaccine. This substudy bridged the period between the end of the efficacy study and the
vaccination of placebo recipients and the initiation of a long-term persistence study. The
study enrolled 14,270 subjects and completed follow-up in May 2007. This substudy is closed
and is in ongoing analysis. The primary results for this study were published in Clinical
Infectious Diseases (Clin Infect Dis. 2012 Nov 15;55(10):1320-1328)
CSP#403C, the Long-Term Persistence Substudy, was initiated in March 2006 and enrolled 6867
vaccine recipients from the main efficacy study. Enrollment was restricted to vaccine
recipients from the main efficacy study with no history of herpes zoster. This study was
initiated to complete an additional five-years of follow-up post-vaccination. The objective
of this study was to estimate the longer-term durability of zoster vaccine efficacy by
following a cohort of vaccine recipients from the primary efficacy study for three study
outcomes: 1) the incidence of herpes zoster, 2) the incidence of postherpetic neuralgia
(PHN), and 3) the burden of illness (BOI) due to herpes zoster. The study completed
surveillance for new cases of herpes zoster as of December 2010 and completed the follow-up
of the last case of herpes zoster in February 2011. All study sites have been closed out.
This substudy has been completed and is in the final analysis phase.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03120364 -
Immunogenicity and Safety of NBP608 Compared to Zostavax in Healthy Adult Aged 50 and Over
|
Phase 3 | |
Completed |
NCT01165203 -
Study to Evaluate GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Human Immunodeficiency Virus (HIV)-Infected Subjects
|
Phase 2 | |
Recruiting |
NCT06088745 -
A Phase Ⅲ Clinical Study to Evaluate Protective Efficacy and Safety of a Recombinant Herpes Zoster Vaccine
|
Phase 3 | |
Completed |
NCT01385566 -
A Study of Intradermal Administration of ZOSTAVAX™ (V211-051 AM2)
|
Phase 1 | |
Completed |
NCT01137669 -
ZOSTAVAX® in Renal Transplant Patients
|
Phase 1 | |
Completed |
NCT01911065 -
T Cell Responses to Varicella Zoster Virus (VZV) Vaccine SLVP020
|
Phase 4 | |
Completed |
NCT00550745 -
ZOSTAVAX™ Safety Study in Subjects ≥ 60 Years of Age (V211-020)
|
Phase 4 | |
Completed |
NCT01132729 -
Bioequivalency Study of Valacyclovir Hydrochloride 1000 mg Under Fasting Conditions
|
N/A | |
Completed |
NCT01132716 -
Bioequivalency Study of Valacyclovir Hydrochloride 1000 mg Under Fed Conditions
|
N/A | |
Completed |
NCT02852876 -
Study to Evaluate the Safety and Pharmacokinetics of Single Doses of ASP2151 in Healthy Male Subjects and the Effects of Food
|
Phase 1 | |
Completed |
NCT00231816 -
A Study of an Investigational Zoster Vaccine in Subjects With a History of Varicella (Chickenpox) Given Concomitantly With Another Vaccine (V211-011)
|
Phase 3 | |
Completed |
NCT05082688 -
Age Differences in Influenza and Herpes Zoster Vaccine Responses (INFLUENZA-SHINGRIX)
|
Phase 2 | |
Completed |
NCT04099706 -
Treatment of Chronic Postherpetic Pain With Autologous Fat Grafting - A RCT
|
N/A | |
Active, not recruiting |
NCT04091451 -
A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline's Herpes Zoster Subunit Vaccine (HZ/su) When Given on a Two-dose Schedule to Adults at Least 50 Years of Age (YOA) Who Had Prior Episode of Shingles
|
Phase 3 | |
Completed |
NCT02519855 -
Study to Evaluate Immunogenicity, Safety, and Tolerability of ZOSTAVAX™ Vaccine (Zoster Vaccine Live, V211) Administered Concomitantly Versus Nonconcomitantly With Quadrivalent Influenza Virus Vaccine (Inactivated) in Participants ≥50 Years of Age (V211-062)
|
Phase 3 | |
Completed |
NCT04523246 -
Training the Innate Immune System Against SARS-CoV-2 (COVID-19) Using the Shingrix Vaccine in Nursing Home Residents
|
Early Phase 1 | |
Completed |
NCT05047770 -
A Study on the Immune Response and Safety of the Shingles Vaccine and the Influenza Vaccine When Either is Given to Healthy Adults at the Same Time or Following a COVID-19 Booster Vaccine
|
Phase 3 | |
Completed |
NCT03314103 -
Efficacy Trial of a Vaccine to Prevent Herpes Zoster in Adults Over 40 Years of Age
|
Phase 3 | |
Completed |
NCT01527370 -
Safety, Tolerability, and Immunogenicity of Zoster Vaccine Live (ZOSTAVAX™) in Healthy Adults in India (V211-025)
|
Phase 3 | |
Completed |
NCT01954251 -
Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Vaccine GSK1437173A When Co-administered With GSK Biologicals' Seasonal Influenza Vaccine GSK2321138A in Adults Aged 50 Years and Older
|
Phase 3 |