E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CMV reactivation after Kidney Transplantation Receiving an Organ from a CMV-Seropositive Donor |
|
E.1.1.1 | Medical condition in easily understood language |
CMV infection, disease, and related complications occuring in people after Kidney Transplantation Receiving an Organ from a CMV-Seropositive Donor |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049107 |
E.1.2 | Term | CMV viraemia |
E.1.2 | System Organ Class | 100000004862 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of ASP0113 compared to placebo in reducing the incidence of CMV viremia (defined as plasma viral load ≥ 1000 IU/mL by central laboratory assay) through one year post first Study Drug injection in CMV-seronegative subjects receiving a kidney from a CMV-seropositive donor. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety of ASP0113 in CMV-seronegative subjects receiving a kidney from a CMV-seropositive donor |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenomics Sub-Study, The retrospective pharmacogenomic research that will be conducted in the future with acquired blood samples is exploratory. The objective of this research is to comprehensively analyze: • Suspected disease-related genes. • Genes of relevance to clinical response, pharmacokinetics, and toxicity/safety issues, to be identified in a precautionary/retrospective setting. |
|
E.3 | Principal inclusion criteria |
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 from a CMVseropositive 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 Randomization. 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 Screening, or 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 Study Period. 7. Female subject must not be breastfeeding at Screening and during the Primary Study Period. 8. Female subject must not donate ova starting at Screening and during the Primary Study Period. 9. Male subject and his 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 Period . *Acceptable forms of birth control include: * Established use of oral, injected or implanted hormonal methods of contraception. * Placement of 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 Period. 11. Subject agrees not to participate in another interventional drug study while on treatment. |
|
E.4 | Principal exclusion criteria |
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 immunoglobulin. 3. Subject has had CMV viremia or CMV disease from time of transplant until time of Randomization. 4. Subject has received, at any time, an organ transplant other than a kidney. (Dual allocation of a kidney is acceptable). 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 treated. 8. Subject required desensitization for ABO blood type incompatibility or a positive T or B cell crossmatch. 9. Subject has received any of the following substances or treatments: a. Investigational research products within 28 days or 5 half lives whichever is longer, prior toTransplantation, 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 a subunit or killed vaccine within 14 days prior to any Study Drug injection. 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 Intravenous (IV) (total daily dose) * 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 are allowed. 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 intramuscular injection. 13. Subject, within 3 days prior to Randomization, has an Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) greater than 3 x Upper Limits of Normal (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. The subject has any other condition which, in the opinion of the Investigator, precludes the subjects participation in the trial. 18. Subject has known allergies or previous adverse reactions to ganciclovir or valganciclovir. 19. Subject has had an allergic reaction to any component of the vaccine, including aminoglycosides, as kanamycin is used during the manufacturing process of the vaccine. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of CMV viremia (defined as plasma viral load of ≥ 1000 IU/mL by central assay) through one year post first Study Drug injection. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Through one year post-transplant. |
|
E.5.2 | Secondary end point(s) |
Incidence of: * Adjudicated CMV 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 [LOQ]) 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. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Through one year post-transplant. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
France |
Germany |
Spain |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of trial in all participating countries is defined as the Last Subject’s Last Visit at the end of the Primary Study Period (Day 395). The Long Term Follow Up will continue after the end of trials’ Primary Study Period. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 30 |