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)
This is a randomized, double-blind (with in-house blinding procedures), placebocontrolled, multicenter study to evaluate the safety, tolerability, efficacy, and immunogenicity of inactivated VZV vaccine for the prevention of HZ in recipients of autologous HCTs. Approximately 1204 patients [?]18 years of age will be enrolled and randomly allocated to receive either inactivated VZV vaccine from one of three consistency lots (~552 patients), inactivated VZV vaccine from a high antigen lot (~100 patients), or placebo (~552 patients), administered in a 4-dose regimen. Randomization will be stratified by intended duration of prophylactic antiviral therapy post-HCT ([?]3 months versus [Greater Than]3 to [?]6 months post-HCT) and by age ([Less Than]50 years of age versus [?] 50 years of age). For this protocol, [?]3 months is defined as [?]90 days and [?]6 months is defined as [?]180 days. The protocol defines the maximum duration of prophylactic antiviral therapy post-HCT as 6 months (180 days).
This will be an event-driven study based on the occurrence of confirmed HZ cases. Patients will remain in the study from the time of enrollment until accrual of the target number (~252) of confirmed HZ cases among inactivated VZV vaccine consistency lot and placebo recipients. A confirmed case of HZ is defined primarily on the basis of detection of VZV DNA in a skin lesion specimen by PCR. For those suspected cases that do not have a diagnostic skin lesion PCR result, either because the result is inadequate or missing, case confirmation will be based on the result of adjudication of the clinical case description by the Clinical Adjudication Committee (CAC), conducted according to the CAC Standard Operations Procedure (SOP).
Patients will be evaluated for safety utilizing a vaccination report card (VRC) following each vaccine dose. Each patient will be followed for at least 1-year following their last vaccination dose. The planned study duration stated in this protocol is estimated based on assumptions of patient enrollment and follow-up times and HZ incidence. If these assumptions are met, patients will be followed for approximately 3 years for the occurrence of suspected HZ, in order to accrue approximately 252 confirmed HZ cases among inactivated VZV vaccine consistency lot and placebo recipients. It should be noted that patients may be followed in the study for less than or more than 3 years, depending on the time that it takes to accrue approximately 252 confirmed cases among inactivated VZV vaccine consistency lot and placebo recipients. In the event that the necessary 252 confirmed cases of HZ among inactivated VZV vaccine consistency lot and placebo recipients accrue sooner than 1 year after the last vaccine dose is administered in this study, the study will continue to allow all patients to complete the 1-year postvaccination follow-up.
Enrollment for the study is expected to be completed in approximately 1 year. The study flow charts are shown in Sections 1.7 and 1.8. The planned randomization schedule by vaccination group is shown in Section 2.4.2. These charts and schedules can be found in the Study Protocol.
A patient will be eligible to participate in this study if all of the following criteria apply.
1. Patient is >=18 years of age on day of signing informed consent.
2. Patient 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 patient is 30 years old, attended primary or secondary school in a country with endemic VZV infection.
3. Patient is scheduled to undergo autologous HCT for treatment of lymphoma or other indication, including any other malignancy or an indication that is not a malignancy within 60 days of enrollment.
4. Patient is highly unlikely to conceive during the time period starting 2 weeks prior to enrollment through 6 months from last vaccination dose, as indicated by at least one "yes" answer to the following questions.
-Patient is a male.
-Patient is a female of reproductive potential who agrees to remain abstinent or use (or have their partner use) adequate contraception during the time period starting 2 weeks prior to enrollment through 6 months from the last vaccination dose. Acceptable methods of birth control include use of hormonal contraceptives, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, tubal ligation, condoms, or abstinence.
-Patient is a female who is not of reproductive potential. A female patient who is not of reproductive potential is defined as: one who has either (1) reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle stimulating hormone [FSH] levels in the postmenopausal range as determined by a laboratory, or 12 months of spontaneous amenorrhea), (2) post-surgical bilateral oophorectomy and/or hysterectomy, or (3) bilateral tubal ligation.
5. All female patients of childbearing potential must have a negative serum or urine pregnancy test.
6. Patient understands the study procedures and agrees to participate in the study by giving written informed consent.
7. Patient is able to understand and complete study questionnaires.