Rasburicase for Hyperuricemia

Condition(s) targeted: Nutritional and Metabolic Diseases

Intervention: SR29142 / Rasburicase (INN) (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Sanofi-Aventis

Official(s) and/or principal investigator(s):
Keiji OHNO, Study Director, Affiliation: Sanofi-Aventis

Primary: To estimate efficacy of SR29142 to the pediatric patients with newly diagnosed hematological malignancies at high risk for Tumor Lysis Syndrome, by evaluation of plasma uric acid concentration.

Secondary: To investigate the safety in this population and anti-SR29142 antibodies, anti-SCP antibodies, and pharmacokinetic parameters.

Official title: Open-Label, Multi-Center Study of SR29142 as Uricolytic Therapy/Prophylaxis for Hyperuricemia in Pediatric Patients With Newly Diagnosed Hematological Malignancies at High Risk for Tumor Lysis Syndrome

Study design: Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Patients with a plasma uric acid level decreased to the endpoint by 48 hr after the start of first drug infusion and lasting until 24 hr after the start of final (Day 5) drug infusion.

Secondary outcome:

Safety will be assessed on clinical observation, laboratory test, vital sign (blood pressure, pulse rate and body temperature), and the occurrence of adverse events.

G6PD activity will be measured in only patients who demonstrate hemolysis.

Anti-SR29142 antibody and Anti-SCP antibody will be measured.

PK parameters.

Minimum age: N/A. Maximum age: 17 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- <18 years of age

- Patient with newly diagnosed hematological malignancies presenting with

hyperuricemia:

- Uric acid > 7. 5 mg/dL in patients ≥ 13 years old- Uric acid > 6. 5mg/dL in patients <13

years old

Or, patient with newly diagnosed hematological malignancies presenting with high tumor burden defined:

- Non-Hodgkin’s lymphoma, Stage IV regardless of uric acid level,

- Non-Hodgkin’s Lymphomas stage III regardless of uric acid level with one of the

following:

- At least one lymph node or mass >5 cm in diameter

- LDH ≥ 3 x ULN (IU/L): Judging according to modified Murphy’s classification

- Acute leukemia with white blood cell count (WBC) ≥ 50,000/mm3 or LDH ≥ 3 x ULN (IU/L)

regardless of uric acid level. etc.

Exclusion Criteria:

- Patients who have received or are scheduled to receive other investigational drugs in

30 days prior to the start of SR29142 administration or during the trial period.

- Low birth weight infant (<2500g) or gestational age <37 weeks

- Patients who have received or are scheduled allopurinol within 72 hrs prior to the

first dose of SR29142 or during the trial period.

- Known history of severe allergic reaction and/or severe asthma.

- Known history or family history of glucose-6-phosphate dehydrogenase deficiency.

- Known history of hemolysis and methemoglobinemia.

- Severe disorders of liver or kidney. ALT (GPT) > 5. 0 x ULN, Total Bilirubin > 3. 0

x ULN, Creatinine > 3. 0 x ULN

- Uncontrollable infections (including viral infections).

- Known positive tests for HBs antigen, HCV antibodies, or HIV-1, 2 antibodies. etc.

Sanofi-Aventis, Tokyo, Japan

Starting date: June 2005
Last updated: September 29, 2006