Valaciclovir Hydrochloride Phase III for Hematopoietic Stem Cell Transplantation Patients

A Multicenter, Open-label Study to Evaluate Preventive Efficacy for Herpes Simplex Virus Infection and Safety of 256U87 (Valaciclovir Hydrochloride) in Adult and Pediatric Hematopoietic Stem Cell Transplantation Patients

The purpose of this study is to evaluate the preventive efficacy for HSV infection and safety of valaciclovir (VACV) in the adult and pediatric HSCT patients.

This clinical study is a multicenter open-label study on the adult and pediatric hematopoietic stem cell transplantation (HSCT) patients. The primary objective is to confirm the preventive efficacy for herpes simplex virus (HSV) infection of 256U87 (VACV: valaciclovir) due to the treatment before or immediately after hematopoietic stem cell transplantation. The secondary objective is to confirm the safety of VACV in the case of its use for such a purpose.

This clinical study consists of the following two periods: the screening period lasting 7 days at the longest and the administration period from 7 days before HSCT to 35 days after HSCT (43 days in total). During the administration period, adult patients are orally given a VACV tablet twice daily, while pediatric patients are orally given VACV granules twice daily at a dose of 25 mg/kg b.w. (maximum dose per treatment: 500 mg). Pediatric patients weighing 40 kg or over may be orally given a VACV tablet twice daily.

Inclusion Criteria:

• Patients who are planning to undergo hematopoietic stem cell transplantation, except cord blood transplantation.
• Patients aged from 1 and above to under 65 at the time of informed consent.
• Patients who can submit their voluntary written informed consent if they are 12 years old and over.
• Patient is male or female. Male patients must be willing to use adequate contraception during the study. Female patients of childbearing potential must agree to consistently perform any of the contraceptive methods.
• QTc <450 msec, or QTc <480 msec in patients with bundle branch block. (values based on either single ECG values or triplicate ECG averaged QTc values)
• Liver test (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2x upper limit of normal (ULN); alkaline phosphatase (Al-P)and total bilirubin <=1.5xULN (total bilirubin >1.5xULN is acceptable if direct bilirubin <35%).

Exclusion Criteria:

• Patients with a history of HSCT.
• Patients who are judged to be in the following condition by the investigator (or subinvestigator): the clinical severity of malabsorption syndrome, vomiting, mucositis or other gastrointestinal dysfunction is so serious that orally administered VACV can not be absorbed.
• Patients who have known nucleoside analogs hypersensitivity.
• Patients who have a concurrent or past history of renal function disorder (serum creatinine >=1.5x ULN).
• Patients who have serious complication (eg, other malignant tumours, cardiac disorder, juvenile diabetes).
• Patients who are currently treated with the prohibited concomitant drugs.
• Patients with evidence of chronic hepatitis B or C.
• Patients with AIDS or patients infected with HIV.
• Patients who were given other trial products within 30 days before initiation of administration of this trial product or those who intend to participate in other clinical trials.
• Patients who are pregnant or probably pregnant.
• Patients who can not follow the protocol because of psychological, family, social or geological reasons.
• Patients are not allowed to participate in this clinical trial if the investigator (or subinvestigator) judges that their participation is inappropriate.