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)

NCT01254630 | Completed Phase 3 Results DMC

• 3 other identifiers: V212-011CTRI/2012/05/0026732010-023156-89
• Study Type: interventional
• Target: 5,305
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Herpes Zoster

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to approximately 5 years

• 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.

  Up to 28 days after vaccination 4 (up to approximately 118 days)

Secondary Outcomes (3)

• Incidence of Moderate to Severe Herpes-Zoster-Associated Pain

  Up to 6 months after onset of HZ (up to approximately 5 years)

• Incidence of Herpes-Zoster Complications

  Up to 6 months after onset of HZ (up to approximately 5 years)

• Incidence of Postherpetic Neuralgia

  Up to 6 months after onset of HZ (up to approximately 5 years)

Other Outcomes (1)

• Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event

  Up to 28 days after vaccination 4 (up to approximately 118 days)

Study Arms (4)

V212-STM

EXPERIMENTAL

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

Biological: V212

V212-HM

EXPERIMENTAL

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

Biological: V212

Placebo-STM

PLACEBO COMPARATOR

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

Biological: Placebo

Placebo-HM

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

V212 BIOLOGICAL

V212 viral antigen for HZ, 0.5 mL subcutaneous (SC) injection per dose, in a four dose regimen, approximately 30 days apart.

Also known as: Inactivated Varicella-Zoster (VZV) vaccine

V212-HM; V212-STM

Placebo BIOLOGICAL

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-HM; Placebo-STM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (4)

• Zorger AM, Hirsch C, Baumann M, Feldmann M, Brockelmann PJ, Mellinghoff S, Monsef I, Skoetz N, Kreuzberger N. Vaccines for preventing infections in adults with haematological malignancies. Cochrane Database Syst Rev. 2025 May 21;5(5):CD015530. doi: 10.1002/14651858.CD015530.pub2.

  PMID: 40396505 DERIVED

• Hirsch C, Zorger AM, Baumann M, Park YS, Brockelmann PJ, Mellinghoff S, Monsef I, Skoetz N, Kreuzberger N. Vaccines for preventing infections in adults with solid tumours. Cochrane Database Syst Rev. 2025 Apr 16;4(4):CD015551. doi: 10.1002/14651858.CD015551.pub2.

  PMID: 40237463 DERIVED

• 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.

  PMID: 32665955 DERIVED

• 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.

  PMID: 31399378 DERIVED

MeSH Terms

Conditions

Herpes Zoster; Hematologic Neoplasms

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2010
• First Posted: December 6, 2010
• Study Start: June 24, 2011
• Primary Completion: April 11, 2017
• Study Completion: April 11, 2017
• Last Updated: September 30, 2019
• Results First Posted: April 13, 2018

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share