Study to Assess the Efficacy and Safety of HX575 in the Treatment of Chemotherapy Associated Anemia in Cancer Patients

Double-blind, Randomized, Multicenter, Clinical Phase III Study to Evaluate the Efficacy and Safety of HX575 for the Treatment of Chemotherapy Associated Anemia in Cancer Patients

This is a randomized, double-blind, multicenter clinical phase III study involving about 105 cancer patients aged >18 years who are receiving palliative chemotherapy and who are suffering from chemotherapy associated anemia. A standard treatment group (ERYPO®) will be included to provide a reference reflecting current standard medical practice.

Eligible patients were randomized to one of two different treatment groups (EPO HEXAL or ERYPO) in a 2:1 ratio. Patients received double-blind treatment for a period of 12 weeks. Following randomization the patients were treated subcutaneously with a dose of 150 IU/kg body weight of study drug three times per week. Dose adjustments to 300 IU/kg body weight three times per week were to be done if hemoglobin (Hb) increased <1.0 g/dL or the reticulocyte count increased <40,000 /μl after 4 weeks or if Hb increased <2.0 g/dL after 8 weeks of treatment. The primary endpoint was the Hb response in the EPO HEXAL group during weeks 5-12 of the study defined as absolute increase in Hb value of 2.0 g/dL from the mean value of the screening/baseline period in the absence of red blood cell transfusion during the preceding 4 weeks. For that purpose, Hb levels were measured at the weekly study visits by a central laboratory. Further parameters of treatment efficacy, safety and tolerability were recorded.

Inclusion Criteria:

• Patients with a confirmed diagnosis of solid tumors
• Patients who receive cyclic palliative chemotherapy with a cycle duration of 1 -4 weeks (for at least 12 weeks) during the study
• Patients with chemotherapy associated anemia (hemoglobin < 10.0 g/dl at screening)
• Life expectancy of at least 6 months Age: > 18
• Eastern Cooperative Oncology Group performance status of 0, 1 or 2
• Serum ferritin greater or equal to 100 µg/l and/or saturated transferrin levels greater or equal to 20 %
• Adequate renal function (serum creatinine below or equal to 2.0 mg/dl)
• Adequate hepatic function (bilirubin < 1.5 times upper limit of normal range
• Patients with ability to follow study instructions, likely to complete all required visits and able to perform the quality of life assessment
• Written informed consent of the patient

Exclusion Criteria:

• Patients who receive curative intended chemotherapy
• Known primary or metastatic malignancy of the central nervous system
• Known primary or metastatic malignancy of bone marrow
• Primary hematologic disorder (e.g. myelodysplastic syndrome, sickle cell anemia, hematological malignancy, acute leukemia)
• Thrombotic events during the last 6 months
• Suspicion or known PRCA (pure red cell aplasia)
• Transfusion of white blood cells or packed red blood cells (more than 2 packs) within 4 weeks and any transfusion of white blood cells or packed red blood cells within 2 weeks prior to randomization (visit 0)
• Anemia due to overt bleeding or hemolysis within 2 weeks before screening
• Erythropoietin or Darbepoietin therapy within 8 weeks before screening, including any investigational form of erythropoietin (e.g. gene-activated erythropoietin, novel erythropoiesis stimulating protein)
• Radiation therapy during the study, radiation therapy induced anemia
• Therapy with cyclosporine
• Chemotherapy which causes predictable treatment with peripheral-blood progenitor therapy, e.g. G-CSF
• Clinical evidence of current uncontrolled hyperparathyroidism (serum parathyroid hormone >1500 pg/mL)
• Major surgery within 14 days prior to randomization
• Treatment with antiepileptics within the last 5 years
• Previously diagnosed HIV or acute hepatitis infection
• Uncontrolled hypertension, defined as a diastolic blood pressure measurement >110mm Hg during the screening period
• History of congestive heart failure (NYHA class III, IV)
• Unstable angina pectoris, active cardiac disease, cardiac infarction during the last six months before screening
• Evidence of acute infectious disease or serious active inflammatory disease within four weeks before screening (Visit -1) or during the screening/baseline period
• Known allergy to one of the ingredients of the test or reference products or hypersensitivity to mammalian-derived products
• Pregnancy, breastfeeding women or women not using adequate birth control measures
• Patients who participate simultaneously in another clinical study or who have participated in a study in the month preceding the start of this study or previously randomized to this study (except studies with approved medications in an approved indication, with an approved dosing regimen including approved treatment combinations)
• Suspicion of any non-compliance