Clinical trial NCT01229267: 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: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Herpes Zoster
Keywords: Herpes zoster
vaccine
herpes zoster-related complications
immunocompromised
autologous hematopoietic cell transplants
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-10-27
Enrollment: 1257
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 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).

Eligibility criteria: 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.

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 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 the onset of HZ rash (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 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: Eriksson J, Hunger M, Bourhis F, Thoren R, Popmihajlov Z, Finelli L, Jiang Y. Cost and utility in immunocompromised subjects who developed herpes zoster during the randomized V212 inactivated varicella-zoster vaccine (ZVIN) trial. Expert Rev Pharmacoecon Outcomes Res. 2020 Dec;20(6):613-621. doi: 10.1080/14737167.2020.1693267. Epub 2019 Nov 18.
citation: Winston DJ, Mullane KM, Cornely OA, Boeckh MJ, Brown JW, Pergam SA, Trociukas I, Zak P, Craig MD, Papanicolaou GA, Velez JD, Panse J, Hurtado K, Fernsler DA, Stek JE, Pang L, Su SC, Zhao Y, Chan ISF, Kaplan SS, Parrino J, Lee I, Popmihajlov Z, Annunziato PW, Arvin A; V212 Protocol 001 Trial Team. Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2018 May 26;391(10135):2116-2127. doi: 10.1016/S0140-6736(18)30631-7. Epub 2018 May 24.