A Study of an Investigational V212/Heat-Treated Varicella-Zoster Virus (VZV) Vaccine in Immunocompromised Adults (V212-002)

• ClinicalTrials.gov Identifier: NCT00535236
• Recruitment Status: Completed
• First Posted: September 26, 2007
• Results First Posted: April 16, 2019
• Last Update Posted: May 20, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

This study will evaluate the safety and immunogenicity of a heat-treated VZV vaccine in autologous or allogeneic hematopoietic cell transplant (HCT) recipients, human immunodeficiency virus (HIV)-infected participants with a baseline cluster of differentiation 4 (CD4) cell count ≤200 cells/mm^3, participants with solid tumor malignancy (STM; breast, colorectal, lung, or ovarian malignancies) receiving chemotherapy, and participants with hematologic malignancy (HM; leukemia or leukemia-like disease, lymphoma or lymphoma-like disease, or multiple myeloma). The primary hypothesis is that the heat-treated VZV vaccine will elicit significant VZV-specific immune responses measured by either glycoprotein-based enzyme-linked immunosorbent assay (gpELISA) or VZV gamma interferon enzyme-linked immunospot (IFN-ELISPOT) at 28 days post dose vaccination 4 in, HIV-infected participants, participants with STM, and participants with HM. The primary immunogenicity objective and endpoints were considered by the protocol as exploratory for the autologous and allogeneic HCT groups.

Condition or disease	Intervention/treatment	Phase
Herpes Zoster; Herpes Zoster-related Complications	Biological: V212; Biological: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 341 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase I, Double-Blind, Randomized, Placebo-Controlled, Multicenter Clinical Trial to Evaluate the Safety and Immunogenicity of V212/Heat-Treated Varicella-Zoster Virus (VZV) Vaccine in Immunocompromised Adults
• Actual Study Start Date: November 2, 2007
• Actual Primary Completion Date: January 25, 2010
• Actual Study Completion Date: January 26, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Autologous HCT-V212; Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: V212; 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days
Placebo Comparator: Autologous HCT-Placebo; Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: Placebo; 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days
Experimental: Allogeneic HCT-V212; Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: V212; 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days
Placebo Comparator: Allogeneic HCT-Placebo; Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: Placebo; 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days
Experimental: STM-V212; Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: V212; 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days
Placebo Comparator: STM-Placebo; Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: Placebo; 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days
Experimental: HM-V212; Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: V212; 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days
Placebo Comparator: HM-Placebo; Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: Placebo; 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days
Experimental: HIV-V212; Participants receive V212 as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: V212; 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days
Placebo Comparator: HIV-Placebo; Participants receive placebo as a 0.65 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: Placebo; 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days

Outcome Measures

Primary Outcome Measures :

1. Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) [ Time Frame: Baseline (Day 1 predose vaccination 1) and 28 days postdose 4 (~Day 118) ]
   Blood sample taken at predose (Day 1) and 28 days post vaccination 4 to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-dose/GMT Pre-vaccination
2. Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by by VZV Interferon-gamma (IFN-g) Enzyme-linked Immunospot (ELISPOT) Assay [ Time Frame: Baseline (Day 1 predose vaccination 1) and 28 days postdose 4 (~Day 118) ]
   Blood sample taken at predose (Day 1) and 28 days post vaccination 4 to determine the geometric mean titre (GMT) of VZV antibodies via ELISPOT. The GMFR was calculated as GMT Post-dose/GMT Pre-vaccination
3. Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE) [ Time Frame: up to 28 days post vaccination 4 (up to ~Day 118) ]
   An SAE was defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants that experienced at least 1 SAE was summarized.

Secondary Outcome Measures :

1. Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card (VRC) [ Time Frame: Up to Day 5 post any vaccination ]
   An adverse event (AE) was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study drug. An AE could therefore have been any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study drug or protocol-specified procedure was also an AE. The percentage of participants with an injection-site AE prompted on the VRC was summarized.
2. Percentage of Participants With a Systemic Adverse Event Prompted on the VRC [ Time Frame: Up to 28 days post vaccination 4 (up to ~118 days) ]
   An adverse event (AE) was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study drug. An AE could therefore have been any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study drug or protocol-specified procedure was also an AE. The percentage of participants with a VRC-prompted systemic (non-injection site) AE was summarized.
3. Percentage of Participants With Elevated Oral Temperature (≥101.0°F (≥38.3ºC) Prompted on the VRC [ Time Frame: Up to 28 days post any vaccination (up to ~118 days) ]
   Participants were instructed on the VRC to take and record their oral (or oral equivalent) temperature daily from the day of vaccination from the date of each vaccine dose through the day prior to the next dose, or for 28 days. Elevated temperature was defined as ≥101.0°F (≥38.3ºC). The percentage of participants that record an elevated temperature was summarized.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men and women > or = to 18 years of age who are scheduled to receive an autologous or allogeneic hematopoietic cell transplant within 60 days of enrollment
• HIV-infected participants with a baseline CD4 cell count < or = to 200 cells/mm^3
• Participants with hematologic malignancies; or participants who are receiving chemotherapy for breast, colorectal, lung, or ovarian malignancies

Exclusion Criteria:

• History of allergy to any vaccine component
• Prior history of HZ
• Prior history of receipt of any varicella or zoster vaccine

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mullane KM, Winston DJ, Wertheim MS, Betts RF, Poretz DM, Camacho LH, Pergam SA, Mullane MR, Stek JE, Sterling TM, Zhao Y, Manoff SB, Annunziato PW. Safety and immunogenicity of heat-treated zoster vaccine (ZVHT) in immunocompromised adults. J Infect Dis. 2013 Nov 1;208(9):1375-85. doi: 10.1093/infdis/jit344. Epub 2013 Aug 1.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00535236
• Other Study ID Numbers: V212-002; 2007_608 ( Other Identifier: Merck ); V212-002 ( Other Identifier: Merck )
• First Posted: September 26, 2007
• Results First Posted: April 16, 2019
• Last Update Posted: May 20, 2019
• Last Verified: May 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Keywords provided by Merck Sharp & Dohme Corp.:

Prevention of herpes zoster and HZ-related complications

Additional relevant MeSH terms:

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