|Principal Investigator: FuadShihab|
|Keywords: Cytomegalovirus , CMV , Kidney Transplant , Infectious Disease , Vaccine||Department: Nephrology|
|IRB Number: 00068907||Co Investigator: LonnieSmith|
|Specialty: Transplant Surgery, Infectious Diseases|
|Sub Specialties: Kidney Transplant, Solid and Bone Marrow Transplant|
Primary Efficacy Endpoints
Incidence of CMV viremia (defined as plasma viral load of ≥ 1000 IU/mL by central assay) through one year post first Study Drug injection.
Secondary Efficacy Endpoints
Incidence of :
Adjudicated CMV-associated disease, including CMV syndrome and CMV tissue invasive disease, through one year post first Study Drug injection.
CMV viremia (defined as plasma viral load ≥ the lower limit of quantification [LLOQ]) by central assay through one year post first Study Drug injection.
Adjudicated CMV-specific antiviral therapy for the treatment of CMV viremia or disease through one year post first Study Drug injection.
Graft survival through one year post first Study Drug injection.
Subject survival through one year post first Study Drug injection.
Exploratory Efficacy Endpoints
Number of opportunistic infections other than CMV through one year post first Study Drug injection.
Time to first CMV viremia (defined as plasma viral load of ≥ 1000 IU/mL by central assay) through one year post study first Study Drug injection.
Time to first adjudicated CMV disease, including CMV syndrome and CMV tissue invasive disease, through one year post first Study Drug injection.
Number of episodes of CMV viral load of ≥ 1000 IU/mL by central assay through one year post first Study Drug injection.
Peak CMV viral load and area under the curve (AUC) through one year post first Study Drug injection.
Viral load area under the curve (AUC), as a measure of “cumulative viral load” through one year post first Study Drug injection.
Number of episodes of adjudicated CMV-associated disease, including CMV syndrome and CMV tissue-invasive disease, through one year post first Study Drug injection.
Number of episodes of viral resistance to ganciclovir or valganciclovir through one year post first Study Drug injection as determined by a central laboratory assay.
Incidence of biopsy-proven (T or B cell) rejection (BPAR)(Banff 2007 Grade > 1) through one year post first Study Drug injection.
Estimated glomerular filtration rate (eGFR) at the last study visit calculated using the 4 variable MDRD formula.
Incidence of clinically treated acute graft rejection through one year post first Study Drug injection.
Patient-reported outcomes through one year post first Study Drug injection.
o EuroQol-5 dimensions 5 levels (EQ-5D)
o Kidney Transplant Questionnaire (KTQ)
o Short Form Health Survey version 2 (SF-12v2)
Healthcare resource utilization through one year post first Study Drug injection.
o Resource use will be collected including the following: hospitalizations recorded as number of days in the Intensive Care Unit, Step-down Unit, and general medical ward (including emergency room visits greater than 24 hours), also non -
protocol -related physician visits and emergency room visits of less than 24 hours.
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written
informed consent and privacy language as per national regulations (e.g., Health Insurance
Portability and Accountability (HIPAA) Authorization for U.S. sites) must be obtained
from the subject or legally authorized representative prior to any study-specific
procedures (including withdrawal of prohibited medication, if applicable).
2. Subject is willing to comply with the protocol.
3. Subject is ≥ 18 years of age or the legal age of consent (whichever is greater).
4. Subject is CMV-seronegative at time of transplant and has received a kidney allograft
from a CMV-seropositive living or deceased donor. CMV serostatus of the recipient can
be determined from 8 weeks prior to transplant, by local laboratory, through day of
transplantation. If CMV serostatus is not available from this time period, CMV serostatus
may be assessed at the Screening Visit, by local laboratory, with results available prior to
5. Subject started valganciclovir or ganciclovir within 10 days of transplant and has received
it through Randomization per regulatory label (package insert).
6. Female subject must be either:
• Of non- child-bearing potential:
o post-menopausal (defined as at least 1 year without any menses) prior to
o documented surgically sterile or status post hysterectomy (at least 1 month
prior to Screening).
• Or, if of childbearing potential:
o must have a negative urine pregnancy test at Screening, and
o if heterosexually active, must use two forms of birth control* (at least one of
which must be a barrier method) starting at Screening and during the Primary
7. Female subject must not be breastfeeding at Screening and during the Primary Study
8. Female subject must not donate ova starting at Screening and during the Primary Study
9. Male subject and their female spouse/partners who are of childbearing potential must be
using highly effective contraception consisting of two forms of birth control* (one of
which must be a barrier method) starting at Screening and during the Primary Study
* Acceptable forms include:
Established use of oral, injected or implanted hormonal methods of contraception.
Placement of an intrauterine device (IUD) or intrauterine system (IUS).
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps)
with spermicidal foam/gel/film/cream/suppository.
Partner male sterilization (i.e., vasectomy)
10. Male subject must not donate sperm starting at Screening and during the Primary Study
11. Subject agrees not to participate in another interventional drug study while on treatment.
1. Subject is planned to undergo a course of CMV-specific prophylactic therapy with
antiviral drugs with a duration of greater than 100 days.
2. Subject has received from one month prior to transplant or is planning to receive CMV
3. Subject has had CMV viremia or CMV disease from time of transplant until time of
4. Subject has received, at any time, an organ transplant other than a kidney. (Dual
allocation of a kidney is allowed).
5. Subject requires dialysis on the day of Randomization.
6. Recipient or donor is known to be positive for human immunodeficiency virus (HIV),
hepatitis B surface antigen, or hepatitis B core IgM or IgG antibody.
7. Subject is known to have latent or active tuberculosis which has not been adequately
8. Subject required desensitization for ABO blood type incompatibility or a positive T or B
9. Subject has received any of the following substances or treatments:
a. Investigational therapy within 28 days or 5 half lives whichever is longer, prior to
Transplantation, or subject is scheduled to receive investigational research products
through one year after Randomization.
b. Alemtuzumab within 90 days prior to Randomization or is scheduled to receive
alemtuzumab any time through one year post Randomization.
c. Rituximab within 120 days prior to Randomization or is scheduled to receive
rituximab any time through one year post Randomization.
d. Eculizumab or bortezomib from the Day of Transplantation through the Day of
Randomization or is scheduled to receive eculizumab or bortezomib any time
through one year post Randomization.
e. IVIG and/or plasmapheresis from Day of Transplant through Day of Randomization.
f. Live attenuated vaccines within one month (30 days) prior to the first dose of Study
Drug or is scheduled to receive live attenuated vaccines within one month of any
Study Drug injection.
g. Subunit or killed vaccines within 14 days prior to the first dose of Study Drug or is
scheduled to receive subunit or killed vaccines within 14 days of any Study Drug
h. Administration of a CMV vaccine, including any prior exposure to ASP0113.
i. Subject has received the following anti-viral therapies or it is planned for them to
receive the AVT for prophylaxis of viral infections in excess of the following doses
from time of transplant through Randomization:
Aciclovir: 1600 mg orally (total daily dose), or 500 mg/m2/dose IV (total daily
Valaciclovir: 1000 mg orally (total daily dose)
Famciclovir: 500 mg orally (total daily dose)
10. Subject has received any anticoagulants including, but not limited to, vitamin K
antagonists, heparin or its derivatives, low molecular weight heparin, factor X inhibitors,
or thrombin inhibitors within 5 half-lives prior to randomization or is expected to use
anticoagulants within 5 half-lives prior to any Study Drug injection. Low dose
anticoagulants that are used for prevention of deep vein thrombosis and antiplatelet agents
11. Subject has any contraindication to or cannot be dosed with valganciclovir or ganciclovir
per package insert on the Day of Randomization for any reason.
12. Subject has, or is expected to have during the Primary Study Period, a contraindication to an
13. Subject, within 3 days prior to Randomization, has an AST or ALT greater than 3 x ULN
or total bilirubin greater than 2 x ULN unless secondary to suspected Gilbert’s disease.
14. Subject has a current malignancy or a recent history of malignancy (within the past 5
years prior to Screening) except non-metastatic basal or squamous cell carcinoma of the
skin that has been treated successfully or cancer in situ of the cervix uteri that has been
successfully treated by local therapy.
15. Subject is being treated for an active infection at the time of Randomization.
16. Subject has any condition or an unstable medical or psychiatric condition, including a
history of illicit drug(s) or alcohol abuse that the Investigator believes will place the
subject at unacceptable risk or interfere with compliance to protocol requirements.
17. Subject has any other condition which, in the opinion of the Investigator, precludes the
subject’s participation in the trial.
18. Subject has known allergies or previous adverse reactions to ganciclovir or
19. Subject has had an allergic reaction to any component of the vaccine, or to amino-glycosides,
as kanamycin is used during the manufacturing process of the vaccine.