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)

NCT01229267 | Completed Phase 3 Results DMC

• 2 other identifiers: V212-0012010-020150-34
• Study Type: interventional
• Target: 1,257
• Locations: 0 countries
• Sites: N/A

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%.

Conditions

Herpes Zoster

Keywords

Herpes zoster; vaccine; herpes zoster-related complications; immunocompromised; autologous hematopoietic cell transplants

Outcome Measures

Primary Outcomes (2)

• Incidence of Confirmed Herpes-Zoster

  Clinical criteria for suspected Herpes-Zoster (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 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 the onset of HZ rash (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 118 days)

Study Arms (5)

V212 Consistency Lot 1

EXPERIMENTAL

Participants randomized to receive V212 consistency Lot 1 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.

Biological: V212

V212 Consistency Lot 2

EXPERIMENTAL

Participants randomized to receive V212 consistency Lot 2 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.

Biological: V212

V212 Consistency Lot 3

EXPERIMENTAL

Participants randomized to receive V212 consistency Lot 3 given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.

Biological: V212

V212 High Antigen Lot

EXPERIMENTAL

Participants randomized to receive V212 High Antigen Lot given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.

Biological: V212

Placebo

PLACEBO COMPARATOR

Participants randomized to receive matching placebo given as a 0.5 mL subcutaneous injection at 30 days before and 30, 60, and 90 days after auto-HCT.

Biological: Matching placebo

Interventions

V212 BIOLOGICAL

V212 viral antigen for HZ. Participants will receive consistency Lot 1, 2, or 3 or the High Antigen Lot.

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

V212 Consistency Lot 1; V212 Consistency Lot 2; V212 Consistency Lot 3; V212 High Antigen Lot

Matching placebo BIOLOGICAL

Vaccine stabilizer for V212 with no virus antigen

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• 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

• 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.

  PMID: 31721601 DERIVED

• 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.

  PMID: 29856344 DERIVED

MeSH Terms

Conditions

Herpes Zoster

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

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: October 25, 2010
• First Posted: October 27, 2010
• Study Start: November 30, 2010
• Primary Completion: December 23, 2015
• Study Completion: December 23, 2015
• Last Updated: September 30, 2019
• Results First Posted: July 2, 2018

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share