E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CMV reactivation after allogeneic stem cell transplantation. |
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E.1.1.1 | Medical condition in easily understood language |
CMV infection, disease, and related complications occuring in people who's immune system has been affected by a bone marrow transplant for leukaemia, MDS or lymphoma. |
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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 |
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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 with placebo as measured by a primary composite endpoint of overall mortality and CMV end organ disease (EOD) through one year post-transplant. • To evaluate the safety of ASP0113 in subjects undergoing allogeneic HCT
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E.2.2 | Secondary objectives of the trial |
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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, 27 March 2013 The pharmacogenomic research that will be conducted in the future with acquired saliva 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.
Donor Sub-Study, 27 March 2013 If a subject has consented and is participating in the optional donor cell sub-study, a 1 mL sample of the donor cell product will be obtained to test for CMV-specific T-cells on the day of transplant (donor cell infusion). |
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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., HIPAA Authorization for U.S. sites) must be obtained from the subject or legally authorized representative prior to any study-specific related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject is a male or female subject who is at least 18 years old or the legal age of consent (whichever is greater). 3. Subject is a CMV-seropositive HCT recipient as confirmed by local laboratory at Screening. 4. Subject is planned to undergo either of the following: a. Sibling Donor Transplant - 7/8 HLA-A, -B, -C, -DRß1 match utilizing high resolution typing or 8/8 HLA-A, -B, -C, -DRß1 match utilizing low or high resolution typing. * b. Unrelated Donor Transplant - 7/8 or 8/8 HLA-A, -B, -C, -DRß1 match utilizing high resolution typing. * * A minimum of 8 allele matching is required. Subjects with matches performed at more than 8 allelles are included if they have 7/8 or 8/8 match at the HLA-A, -B, -C. –DRß1 alleles. 5. Subject is scheduled to receive an allogeneic peripheral blood stem cell (PBSC) or bone marrow transplant (BMT) for the treatment of hematologic disorders as indicated in Inclusion Criterion 6. 6. Subject has one of the following underlying diseases a. Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission or in early relapse (< 20% blasts in bone marrow with no circulating blasts in peripheral blood and no extramedullary leukemia). b. Acute lymphoblastic leukemia (ALL), in first or second complete remission. c. Acute undifferentiated leukemia (AUL) in first or second complete remission. d. Acute biphenotypic leukemia in first or second complete remission. e. Chronic myelogenous leukemia (CML) in either chronic or accelerated phase. f. Chronic lymphocytic leukemia (CLL). g. One of the following myelodysplastic syndrome(s) (MDS) defined by the following: i. Refractory anemia with evidence of dysplasia. ii. Refractory anemia with ringed sideroblasts. iii. Refractory cytopenia with multilineage dysplasia. iv. Refractory cytopenia with multilineage dysplasia and ringed sideroblasts. v. Refractory anemia with excess blasts-1 (5-10% blasts). vi. Refractory anemia with excess blasts-2 (10-20% blasts). vii. Myelodysplastic syndrome (MDS), unclassified. viii. MDS associated with isolated del (5q). ix. Chronic myelomonocytic leukemia (CMML). h. Primary or secondary myelofibrosis without leukemic transformation except if Dynamic International Prognostic Scoring System (DIPSS) category of high or intermediate-2. i. Lymphoma (including Hodgkin’s) with chemosensitive disease (> 50% response to chemotherapy). 7. 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 and if < 50 years of age and not documented to be surgically sterile must have a negative urine or serum pregnancy test at 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 or serum pregnancy test at Screening, and o if heterosexually active, must use at least one form of birth control* (which must be a barrier method) starting at Screening and through the Primary Study Period. 8. Female subject must not be breastfeeding at Screening, through the treatment period and through the Primary Study Period. 9. Female subject must not donate ova starting at Screening, through the treatment period and through the Primary Study. 10. Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control* (1 of which must be a barrier method) starting at Screening, through the treatment period and through the Primary Study Period. * Acceptable forms include: • Consistent and correct usage of established oral contraception. • Established 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
11. Male subject must not donate sperm starting at Screening, through the treatment period and through the Primary Study Period. 12. Subject is willing to comply with the protocol. 13. Subject agrees not to participate in another interventional study while on treatment. New regimens of approved chemotherapeutic drugs or antibodies, conditioning drugs, irradiation and T-cell depleting antibodies, except alemtuzumab, are allowed. |
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E.4 | Principal exclusion criteria |
1. Subject has active CMV disease or infection or has received treatment for active CMV disease or infection within 3 months (90 days) prior to transplant. 2. Subject has planned CMV prophylactic therapy with antiviral drugs or CMV-specific immunoglobulins from randomization through the primary study period completion/Day 365 Visit (V 14). 3. Subject has a modified hematopoietic cell transplant comorbidity index (HCT-CI) score ≥ 4. 4. Subject is known to be positive for human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C RNA polymerase chain reaction (PCR). 5. Donor CMV serostatus is unknown. 6. Subject has received any of the following substances or treatments: a. Alemtuzumab within 60 days prior to transplant, including conditioning regimen. Subjects for whom treatment with alemtuzumab is planned at any time from 60 days prior to through one year post-transplant should not be enrolled in the trial. b. T cell depletion of donor cell product. c. Administration of a CMV vaccine, including any prior exposure to ASP0113. 7. Subject has received an allogeneic stem cell transplant within one year prior to transplant (subjects who have received a prior autologous transplant are allowed). 8. Subject has a current malignancy in addition to the malignancy being treated for the study or the subject has a history of any other 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 handled by local surgery. 9. Subject has an unstable medical or psychiatric condition, including a history of illicit drug(s) or alcohol abuse that the Investigator believes will interfere with protocol requirements. 10. Subject has had an allergic reaction to any component of the vaccine. Subject has had an allergic reaction to aminoglycosides as kanamycin is used in the manufacturing process of the vaccine. 11. Subject has participated in any interventional clinical study or has been treated with any investigational research products within 30 days or 5 halflives, whichever is longer, prior to the initiation of Screening. (Investigational research products are considered those products that have not been approved for any indication in the country where the subject is enrolled. New regimens of approved chemotherapeutic drugs or antibodies, conditioning drugs, irradiation and T-cell depleting antibodies, except alemtuzumab, are allowed.) 12. Subject has received a prior HCT and has residual cGVHD. 13. Subject who is scheduled to have a cord blood transplant or a haploidentical transplant. 14. Subject has a platelet count of less than 50,000 mm3 within 3 days prior to randomization (platelet transfusions are allowed). Results received in an equivalent local unit of measure must be converted to SI units. 15. Subject has aplastic anemia or multiple myeloma. 16. For sites in Japan only: Other subjects considered ineligible by the Investigator/sub-Investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the composite of overall mortality and CMV EOD through 1 year post-transplant. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Through one year post-transplant. |
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E.5.2 | Secondary end point(s) |
• Time to first protocol-defined CMV viremia load [CMV plasma viral ≥ 1000 IU/mL as assessed by the central laboratory] through 1 year post-transplant. • Time to first adjudicated CMV-specific AVT through 1 year post –transplant. • Time to first CMV-specific AVT for protocol-defined CMV viremia [CMV plasma viral load ≥ 1000 IU/mL as assessed by the central laboratory] or CMV EOD through one year post-transplant. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Through one year post-transplant. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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 | 36 |
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 |
Belgium |
Canada |
France |
Germany |
Japan |
Korea, Democratic People's Republic of |
Spain |
Sweden |
Taiwan |
United States |
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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
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For regulatory reporting purposes, the end of the trial will be the last visit of the last subject during the primary study period (day 365/Visit 14). An addendum to the clinical study report will be prepared after completion of the long-term follow up period (5.5 years post transplant). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |