Efficacy and Safety Study of CSJ148 in Stem Cell Transplant Patients

Inclusion Criteria

Patients eligible for inclusion in this study had to fulfill all of the following criteria:

• Written informed consent must be obtained before any assessment was performed.
• Male and female patients at least 18 years of age.
• Patients weighed between 45 -120 kg to participate in the study, and had a body mass index (BMI) within the range of 18 - 34 kg/m2
• Scheduled to undergo allogeneic bone marrow, peripheral blood stem cell, or cord blood transplantation (transplant may be related or unrelated, T-cell depleted or non-T-cell depleted, myeloablative or non-myeloablative/reduced intensity, haploidentical) and began conditioning chemotherapy within 48 hours of planned dosing day.
• Patient seropositive for HCMV before transplantation; donor could be seropositive or seronegative for HCMV (donor positive/recipient or donor negative/recipient positive). Historical patient HCMV serology data collected within the last 12 months or local assays could be used to qualify the patient for enrollment.
• Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Exclusion Criteria

Patients fulfilling any of the following criteria were not eligible for inclusion in this study:

• Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or until the expected PD (pharmacodynamic) effect has returned to baseline, whichever is longer; or longer if required by local regulations.
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
• Karnofsky performance score 25 mg/kg/day IV), valacyclovir (>3 gm/day oral), famciclovir (>1500 mg/day oral), HCMV immune globulin, immune globulin (>500 mg/kg), or any other medication with anti-HCMV activity.
• Required mechanical ventilation within 7 days prior to enrollment.
• Received any vasopressors or other agents for hemodynamic support within 7 days prior to enrollment. These agents included but are not limited to epinephrine, metaraminol, norepinephrine, dopamine, vasopressin, phenylephrine, and dobutamine.
• Impaired renal function requiring dialysis.
• Any surgical or medical condition which might increase the risk for thrombotic events if given immunoglobulins. These conditions included cryoglobulinemia, monoclonal gammopathies, and hypertriglyceridemia (fasting level >1000 mg/dL). The investigator should make this determination in consideration of the subject's medical history and laboratory data.
• Severe liver disease or liver injury as indicated one or more of the following:
• Alanine aminotransferase (ALT) >5-times the upper limit of normal (ULN).
• Aspartate aminotransferase (AST) >5-times the upper limit of normal.
• Gamma-glutamyl transferase (γ-GT) >5-times the upper limit of normal.
• Serum total bilirubin (TBL) >3-times the upper limit of normal.
• Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using effective methods of contraception during dosing of study treatment.

Effective contraception methods included:

• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman was confirmed by follow up hormone level assessment.
• Male sterilization (at least 6 months prior to screening). For female patients o