A Study to Evaluate the Safety and Efficacy of Inactivated Varicella-zoster Vaccine (VZV) as a Preventative Treatment for Herpes Zoster (HZ) and HZ-related Complications in Adult Participants With Solid Tumor or Hematologic Malignancy (V212-011)

Study Description

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Brief Summary:

This is a randomized, double-blind, placebo-controlled study to assess the safety and tolerability of V212 when administered to adults with solid tumor malignancy (STM) receiving chemotherapy and to assess the impact of V212 on the development of herpes zoster (HZ) in adults with STM receiving chemotherapy. The primary hypothesis is that vaccination with V212 will reduce the incidence of HZ compared with placebo in adults with STM (lower bound of the 97.5% {one-sided α=0.0125} confidence interval [CI] for the estimated vaccine efficacy in adults with STM be >25%).

Participants with hematologic malignancy (HM) were also enrolled and were to be originally included in the primary and secondary objectives and analyses. After an interim analysis demonstrated clear evidence of futility of V212 in the HM population, enrollment of this population was stopped and all HM-related objectives and analyses were made exploratory and are not reported in this record.

Condition or disease	Intervention/treatment	Phase
Herpes Zoster	Biological: V212; Biological: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	5305 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Prevention
Official Title:	A Phase III Randomized, Placebo-Controlled, Clinical Trial to Study the Safety and Efficacy of V212 in Adult Patients With Solid Tumor or Hematologic Malignancy
Actual Study Start Date :	June 24, 2011
Actual Primary Completion Date :	April 11, 2017
Actual Study Completion Date :	April 11, 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: V212-STM; Participants with STM receiving chemotherapy randomized to receive V212 vaccine given as a 4-dose regimen administered ~30 days apart.	Biological: V212; V212 viral antigen for HZ, 0.5 mL subcutaneous (SC) injection per dose, in a four dose regimen, approximately 30 days apart.; Other Name: Inactivated Varicella-Zoster (VZV) vaccine
Experimental: V212-HM; Participants with HM randomized to receive V212 vaccine given as a 4-dose regimen administered ~30 days apart.	Biological: V212; V212 viral antigen for HZ, 0.5 mL subcutaneous (SC) injection per dose, in a four dose regimen, approximately 30 days apart.; Other Name: Inactivated Varicella-Zoster (VZV) vaccine
Placebo Comparator: Placebo-STM; Participants with STM receiving chemotherapy randomized to receive placebo to V212 vaccine given as a 4-dose regimen administered ~30 days apart.	Biological: Placebo; Vaccine stabilizer for V212 with no virus antigen, 0.5 mL SC injection per dose, in a four dose regimen, approximately 30 days apart.
Placebo Comparator: Placebo-HM; Participants with HM randomized to receive placebo to V212 vaccine given as a 4-dose regimen administered ~30 days apart.	Biological: Placebo; Vaccine stabilizer for V212 with no virus antigen, 0.5 mL SC injection per dose, in a four dose regimen, approximately 30 days apart.

Outcome Measures

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Primary Outcome Measures :

1. Incidence of Confirmed Herpes-Zoster [ Time Frame: Up to approximately 5 years ]
   Clinical criteria for suspected HZ cases were the development of a papular or vesicular rash with a dermatomal or generalized distribution, or in the absence of a rash, clinical suspicion of VZV infection with or without the detection of VZV in diagnostic specimens from blood, cerebrospinal fluid, lung, liver, or other organ. All suspected cases of HZ were subjected to adjudication by the Clinical Adjudication Committee (CAC). Case confirmation was based on skin lesion polymerase chain reaction, if available, or by adjudication of the clinical case description by the CAC, conducted according to the CAC Standard Operations Procedure.
2. Percentage of Participants With One or More Serious Adverse Events [ Time Frame: Up to 28 days after vaccination 4 (up to approximately 118 days) ]
   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 sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event.

Secondary Outcome Measures :

1. Incidence of Moderate to Severe Herpes-Zoster-Associated Pain [ Time Frame: Up to 6 months after onset of HZ (up to approximately 5 years) ]
   Moderate to severe HZ-associated pain was defined as 2 or more occurrences of a score of 3 or greater (0-to-10 scale, where 0 is no pain and 10 is pain as bad as you can imagine) on the Zoster Brief Pain Inventory (ZBPI) at any time from HZ onset through the end of the 6 month HZ-follow-up period.
2. Incidence of Herpes-Zoster Complications [ Time Frame: Up to 6 months after onset of HZ (up to approximately 5 years) ]
   The composite efficacy endpoint of the incidence of HZ complications was defined as the occurrence of any of the following during the study: hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, or administration of intravenous acyclovir therapy for treatment of HZ.
3. Incidence of Postherpetic Neuralgia [ Time Frame: Up to 6 months after onset of HZ (up to approximately 5 years) ]
   Postherpetic Neuralgia (PHN) was defined as pain in the area of the HZ rash with pain in the last 24 hours scored as 3 or greater (on a 0 to 10 scale, where 0 is no pain and 10 is pain as bad as you can imagine) on the ZBPI that persists or appears greater than or equal to 90 days after HZ rash onset.

Other Outcome Measures:

1. Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event [ Time Frame: Up to 28 days after vaccination 4 (up to approximately 118 days) ]
   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 sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

• Has been diagnosed with an STM or HM and is not likely to undergo hematopoietic cell transplant (HCT) and is either ≥18 years of age and receiving a cytotoxic or immunosuppressive chemotherapy regimen OR is ≥ 50 years of age with a hematologic malignancy that is not in remission, whether on therapy or not
• Life expectancy ≥12 months
• Has prior history of varicella, antibodies to VZV (documented prior to receipt of blood products), or residence in a country with endemic VZV infection for ≥30 years or if participant is <30 years old, attended primary or secondary school in a country with endemic VZV infection
• Is highly unlikely to conceive during the time period starting 2 weeks prior to enrollment through 6 months from last vaccination dose
• Female participants of childbearing potential must have a negative serum or urine pregnancy test

Exclusion criteria:

• History of hypersensitivity reaction to any vaccine component
• Prior history of Herpes Zoster within 1 year of enrollment
• Has received or is expected to receive any varicella or non-study zoster vaccine
• Currently receiving or expected to receive long-term antiviral prophylaxis (>4 weeks duration) with activity against herpes simplex virus (HSV), VZV or cytomegalovirus (CMV)
• Is pregnant or breastfeeding or expecting to conceive within the period of 2 weeks prior to enrollment throughout 6 months from last vaccination dose
• Has received a live virus vaccine or is scheduled to receive a live virus vaccine in the period from 4 weeks prior to Dose 1 through 28 days Postdose 4
• Has received an inactivated vaccine or is scheduled to receive an inactivated vaccine in the period between 7 days prior to and 28 days following Doses 1 through 4

Contacts and Locations

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Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

Study Director:	Medical Director	Merck Sharp & Dohme Corp.

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:

Study Protocol and Statistical Analysis Plan  [PDF] June 30, 2015

More Information

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Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT01254630 History of Changes
Other Study ID Numbers:	V212-011; CTRI/2012/05/002673 ( Registry Identifier: CTRI ); 2010-023156-89 ( EudraCT Number ); V212-011 ( Other Identifier: Merck Protocol Number )
First Posted:	December 6, 2010
Results First Posted:	April 13, 2018
Last Update Posted:	April 13, 2018
Last Verified:	March 2018

Keywords provided by Merck Sharp & Dohme Corp.:

Herpes zoster; vaccine; herpes-zoster-related complications; immunocompromised	herpes zoster-associated pain; solid tumor malignancy; hematologic malignancy

Additional relevant MeSH terms:

Neoplasms; Herpes Zoster; Herpesviridae Infections; DNA Virus Infections	Virus Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs