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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 Participants Undergoing Hematopoietic Cell Transplants (HCTs) (V212-001)

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ClinicalTrials.gov Identifier: NCT01229267
Recruitment Status : Completed
First Posted : October 27, 2010
Results First Posted : July 2, 2018
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE October 25, 2010
First Posted Date  ICMJE October 27, 2010
Results First Submitted Date  ICMJE April 16, 2018
Results First Posted Date  ICMJE July 2, 2018
Last Update Posted Date September 30, 2019
Actual Study Start Date  ICMJE November 30, 2010
Actual Primary Completion Date December 23, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2018)
  • Incidence of Confirmed Herpes-Zoster [ Time Frame: Up to approximately 5 years ]
    Clinical criteria for suspected Herpes-Zoster (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.
  • Percentage of Participants With One or More Serious Adverse Events [ Time Frame: Up to 28 days after vaccination 4 (up to 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 26, 2010)
Incidence of herpes zoster (HZ) [ Time Frame: Approximately 3 years ]
Incidence is defined as the number of HZ cases per 1000 person-years of follow-up from study enrollment to the end of study.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2018)
  • 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 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.
  • 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.
  • Incidence of Postherpetic Neuralgia [ Time Frame: Up to 6 months after the onset of HZ rash (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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2010)
  • Incidence of moderate to severe HZ-associated pain [ Time Frame: From HZ onset through the end of the 6 month HZ-follow-up period ]
    Moderate to severe HZ-associated pain (defined as 2 or more occurrences of a score of 3 or greater (0-to-10 scale) on the Zoster Brief Pain Inventory [ZBPI]),
  • Incidence of HZ complications [ Time Frame: Approximately 3 years ]
    HZ complications 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.
  • Incidence of postherpetic neuralgia (PHN) [ Time Frame: Onset of HZ rash up to 6-month follow-up ]
    Postherpetic neuralgia (PHN) is defined as a worst pain score [in the last24 hours] of 3 or greater [0-to-10 scale] on the Zoster Brief Pain Inventory (ZBP that persists or appears more than 90 days after the onset of the HZ rash
Current Other Pre-specified Outcome Measures
 (submitted: June 1, 2018)
Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event [ Time Frame: Up to 28 days after vaccination 4 (up to 118 days) ]
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 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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 Participants Undergoing Hematopoietic Cell Transplants (HCTs) (V212-001)
Official Title  ICMJE A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Clinical Trial to Study the Safety, Tolerability, Efficacy, and Immunogenicity of V212 in Recipients of Autologous Hematopoietic Cell Transplants (HCTs)
Brief Summary This is a randomized, double-blind, placebo-controlled study to assess the safety and efficacy of inactivated VZV vaccine for the prevention of HZ and HZ-related complications in adult recipients of autologous hematopoietic cell transplants (HCTs). The primary hypothesis is that vaccination with V212 vaccine will reduce the incidence of herpes zoster (HZ) compared to placebo when administered to recipients of HCT. The statistical criterion for success requires that the lower bound of the 95% confidence interval for the estimated vaccine efficacy in the V212 recipients (excluding the high-antigen lot) compared with that in the placebo recipients is >25%.
Detailed Description Study participants were randomized to receive one of 3 consistency lots of V212, a high antigen lot of V212, or placebo. To comply with regulatory requests, results for all lots of V212 were combined for the primary and secondary efficacy and safety evaluations (Protocol Amendment 2); all planned comparisons between the V212 lots were exploratory and are not included in this disclosure. Further, by regulatory request, the V212 High Antigen Lot was not included in the efficacy analyses for concerns that its inclusion would inflate the efficacy estimates (Protocol Amendment 4).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Herpes Zoster
Intervention  ICMJE
  • Biological: V212
    V212 viral antigen for HZ. Participants will receive consistency Lot 1, 2, or 3 or the High Antigen Lot.
    Other Name: Inactivated Varicella-Zoster (VZV) vaccine
  • Biological: Matching placebo
    Vaccine stabilizer for V212 with no virus antigen
Study Arms  ICMJE
  • Experimental: V212 Consistency Lot 1
    Participants randomized to receive V212 consistency Lot 1 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
    Intervention: Biological: V212
  • Experimental: V212 Consistency Lot 2
    Participants randomized to receive V212 consistency Lot 2 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
    Intervention: Biological: V212
  • Experimental: V212 Consistency Lot 3
    Participants randomized to receive V212 consistency Lot 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
    Intervention: Biological: V212
  • Experimental: V212 High Antigen Lot
    Participants randomized to receive V212 High Antigen Lot given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
    Intervention: Biological: V212
  • Placebo Comparator: Placebo
    Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.
    Intervention: Biological: Matching placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 29, 2015)
1257
Original Estimated Enrollment  ICMJE
 (submitted: October 26, 2010)
1204
Actual Study Completion Date  ICMJE December 23, 2015
Actual Primary Completion Date December 23, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • Scheduled to undergo an autologous hematopoietic cell transplant within 60 days of enrollment
  • 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
  • Prior receipt of any varicella or zoster vaccine
  • More than 2 relapses of the underlying cancer (participants with Hodgkin's lymphoma may have had more than 2 relapses)
  • Expectation of tandem transplant procedure
  • Is expected to receive >6 months (>180 days) of prophylactic antiviral therapy post-HCT.
  • Is pregnant or breastfeeding or expecting to conceive within the period of 2 weeks prior to enrollment through 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Argentina,   Australia,   Belgium,   Brazil,   Canada,   Colombia,   Croatia,   Czech Republic,   Ecuador,   France,   Germany,   Israel,   Italy,   Korea, Republic of,   Lithuania,   Mexico,   Netherlands,   Panama,   Peru,   Portugal,   Puerto Rico,   Russian Federation,   Spain,   Sweden,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT01229267
Other Study ID Numbers  ICMJE V212-001
2010-020150-34 ( EudraCT Number )
V212-001 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP