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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 Adult Participants With Solid Tumor or Hematologic Malignancy (V212-011)

Primary Purpose

Herpes Zoster

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
V212
Placebo
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Herpes Zoster focused on measuring Herpes zoster, vaccine, herpes-zoster-related complications, immunocompromised, herpes zoster-associated pain, solid tumor malignancy, hematologic malignancy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Placebo Comparator

    Arm Label

    V212-STM

    V212-HM

    Placebo-STM

    Placebo-HM

    Arm Description

    Participants with STM receiving chemotherapy randomized to receive V212 vaccine given as a 4-dose regimen administered ~30 days apart.

    Participants with HM randomized to receive V212 vaccine given as a 4-dose regimen administered ~30 days apart.

    Participants with STM receiving chemotherapy randomized to receive placebo to V212 vaccine given as a 4-dose regimen administered ~30 days apart.

    Participants with HM randomized to receive placebo to V212 vaccine given as a 4-dose regimen administered ~30 days apart.

    Outcomes

    Primary Outcome Measures

    Incidence of Confirmed Herpes-Zoster
    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.
    Percentage of Participants With One or More Serious Adverse Events
    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

    Incidence of Moderate to Severe Herpes-Zoster-Associated Pain
    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.
    Incidence of Herpes-Zoster Complications
    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
    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.

    Full Information

    First Posted
    December 3, 2010
    Last Updated
    September 10, 2019
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01254630
    Brief Title
    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)
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    June 24, 2011 (Actual)
    Primary Completion Date
    April 11, 2017 (Actual)
    Study Completion Date
    April 11, 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Herpes Zoster
    Keywords
    Herpes zoster, vaccine, herpes-zoster-related complications, immunocompromised, herpes zoster-associated pain, solid tumor malignancy, hematologic malignancy

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    5305 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    V212-STM
    Arm Type
    Experimental
    Arm Description
    Participants with STM receiving chemotherapy randomized to receive V212 vaccine given as a 4-dose regimen administered ~30 days apart.
    Arm Title
    V212-HM
    Arm Type
    Experimental
    Arm Description
    Participants with HM randomized to receive V212 vaccine given as a 4-dose regimen administered ~30 days apart.
    Arm Title
    Placebo-STM
    Arm Type
    Placebo Comparator
    Arm Description
    Participants with STM receiving chemotherapy randomized to receive placebo to V212 vaccine given as a 4-dose regimen administered ~30 days apart.
    Arm Title
    Placebo-HM
    Arm Type
    Placebo Comparator
    Arm Description
    Participants with HM randomized to receive placebo to V212 vaccine given as a 4-dose regimen administered ~30 days apart.
    Intervention Type
    Biological
    Intervention Name(s)
    V212
    Other Intervention Name(s)
    Inactivated Varicella-Zoster (VZV) vaccine
    Intervention Description
    V212 viral antigen for HZ, 0.5 mL subcutaneous (SC) injection per dose, in a four dose regimen, approximately 30 days apart.
    Intervention Type
    Biological
    Intervention Name(s)
    Placebo
    Intervention Description
    Vaccine stabilizer for V212 with no virus antigen, 0.5 mL SC injection per dose, in a four dose regimen, approximately 30 days apart.
    Primary Outcome Measure Information:
    Title
    Incidence of Confirmed Herpes-Zoster
    Description
    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.
    Time Frame
    Up to approximately 5 years
    Title
    Percentage of Participants With One or More Serious Adverse Events
    Description
    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.
    Time Frame
    Up to 28 days after vaccination 4 (up to approximately 118 days)
    Secondary Outcome Measure Information:
    Title
    Incidence of Moderate to Severe Herpes-Zoster-Associated Pain
    Description
    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.
    Time Frame
    Up to 6 months after onset of HZ (up to approximately 5 years)
    Title
    Incidence of Herpes-Zoster Complications
    Description
    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.
    Time Frame
    Up to 6 months after onset of HZ (up to approximately 5 years)
    Title
    Incidence of Postherpetic Neuralgia
    Description
    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.
    Time Frame
    Up to 6 months after onset of HZ (up to approximately 5 years)
    Other Pre-specified Outcome Measures:
    Title
    Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
    Description
    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.
    Time Frame
    Up to 28 days after vaccination 4 (up to approximately 118 days)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    32665955
    Citation
    Boeckh MJ, Arvin AM, Mullane KM, Camacho LH, Winston DJ, Morrison VA, Hurtado K, Durrand Hall J, Pang L, Su SC, Kaplan SS, Annunziato PW, Popmihajlov Z; V212 Protocol 001 Trial Group and V212 Protocol 011 Trial Group. Immunogenicity of Inactivated Varicella Zoster Vaccine in Autologous Hematopoietic Stem Cell Transplant Recipients and Patients With Solid or Hematologic Cancer. Open Forum Infect Dis. 2020 Jun 2;7(7):ofaa172. doi: 10.1093/ofid/ofaa172. eCollection 2020 Jul.
    Results Reference
    derived
    PubMed Identifier
    31399378
    Citation
    Mullane KM, Morrison VA, Camacho LH, Arvin A, McNeil SA, Durrand J, Campbell B, Su SC, Chan ISF, Parrino J, Kaplan SS, Popmihajlov Z, Annunziato PW; V212 Protocol 011 Trial Team. Safety and efficacy of inactivated varicella zoster virus vaccine in immunocompromised patients with malignancies: a two-arm, randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2019 Sep;19(9):1001-1012. doi: 10.1016/S1473-3099(19)30310-X. Epub 2019 Aug 6. Erratum In: Lancet Infect Dis. 2019 Aug 23;:
    Results Reference
    derived

    Learn more about this trial

    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)

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