- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01254630
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)
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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.
|
V212 viral antigen for HZ, 0.5 mL subcutaneous (SC) injection per dose, in a four dose regimen, approximately 30 days apart.
Other Names:
|
Experimental: V212-HM
Participants with HM randomized to receive V212 vaccine given as a 4-dose regimen administered ~30 days apart.
|
V212 viral antigen for HZ, 0.5 mL subcutaneous (SC) injection per dose, in a four dose regimen, approximately 30 days apart.
Other Names:
|
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.
|
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.
|
Vaccine stabilizer for V212 with no virus antigen, 0.5 mL SC injection per dose, in a four dose regimen, approximately 30 days apart.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to approximately 5 years
|
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.
|
Up to 28 days after vaccination 4 (up to approximately 118 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 6 months after onset of HZ (up to approximately 5 years)
|
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.
|
Up to 6 months after onset of HZ (up to approximately 5 years)
|
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.
|
Up to 6 months after onset of HZ (up to approximately 5 years)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 28 days after vaccination 4 (up to approximately 118 days)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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.
- 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;:
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Virus Diseases
- Infections
- Neoplasms by Site
- Hematologic Diseases
- DNA Virus Infections
- Skin Diseases, Infectious
- Skin Diseases, Viral
- Herpesviridae Infections
- Varicella Zoster Virus Infection
- Neoplasms
- Hematologic Neoplasms
- Herpes Zoster
- Herpes Simplex
- Physiological Effects of Drugs
- Immunologic Factors
- Vaccines
Other Study ID Numbers
- V212-011 (Other Identifier: Merck Protocol Number)
- CTRI/2012/05/002673 (Registry Identifier: CTRI)
- 2010-023156-89 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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