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)
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Herpes Zoster
Keywords: Herpes zoster
vaccine
herpes-zoster-related complications
immunocompromised
herpes zoster-associated pain
solid tumor malignancy
hematologic malignancy
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-12-06
Enrollment: 5305
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Incidence of Confirmed Herpes-Zoster
timeFrame: Up to approximately 5 years
measure: Percentage of Participants With One or More Serious Adverse Events
timeFrame: Up to 28 days after vaccination 4 (up to approximately 118 days)
Secondary outcomes:
measure: Incidence of Moderate to Severe Herpes-Zoster-Associated Pain
timeFrame: Up to 6 months after onset of HZ (up to approximately 5 years)
measure: Incidence of Herpes-Zoster Complications
timeFrame: Up to 6 months after onset of HZ (up to approximately 5 years)
measure: Incidence of Postherpetic Neuralgia
timeFrame: Up to 6 months after onset of HZ (up to approximately 5 years)
Other outcomes:
measure: Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
timeFrame: Up to 28 days after vaccination 4 (up to approximately 118 days)
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.
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.