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

Study Overview
=================
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.

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

Conditions
-----------------
Herpes Zoster, Herpes Zoster-related Complications

Intervention / Treatment
-----------------
* Biological: V212
* Biological: Placebo


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous HCT-V212<br>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<br>* 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days<br>|
| Placebo Comparator: Autologous HCT-Placebo<br>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<br>* 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days<br>|
| Experimental: Allogeneic HCT-V212<br>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<br>* 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days<br>|
| Placebo Comparator: Allogeneic HCT-Placebo<br>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<br>* 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days<br>|
| Experimental: STM-V212<br>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<br>* 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days<br>|
| Placebo Comparator: STM-Placebo<br>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<br>* 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days<br>|
| Experimental: HM-V212<br>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<br>* 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days<br>|
| Placebo Comparator: HM-Placebo<br>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<br>* 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days<br>|
| Experimental: HIV-V212<br>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<br>* 0.65 ml V212 in 4 dose regimen. Treatment period of 125 days<br>|
| Placebo Comparator: HIV-Placebo<br>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<br>* 0.65 ml V212 Pbo in 4 dose regimen. Treatment period of 125 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) | 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 | Baseline (Day 1 predose vaccination 1) and 28 days postdose 4 ( Day 118) | 
| Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by by VZV Interferon-gamma (IFN-g) Enzyme-linked Immunospot (ELISPOT) Assay | 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 | Baseline (Day 1 predose vaccination 1) and 28 days postdose 4 ( Day 118) | 
| Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE) | 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. | up to 28 days post vaccination 4 (up to  Day 118) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card (VRC) | 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. | Up to Day 5 post any vaccination | 
| Percentage of Participants With a Systemic Adverse Event Prompted on the VRC | 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. | Up to 28 days post vaccination 4 (up to  118 days) | 
| Percentage of Participants With Elevated Oral Temperature (≥101.0°F (≥38.3ºC) Prompted on the VRC | 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. | Up to 28 days post any vaccination (up to  118 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prevention of herpes zoster and HZ-related complications