Treatment of Anemia in Hemodialysis Patients Previously Treated With Epoetin MedDRA version: 8.1 Level: LLT Classification code 10002272 Term: Anemia
Conditions
Interventions
Product Name: Hematide
Product Code: AF37702 Injection,
Pharmaceutical Form: Solution for injection
Current Sponsor code: AF37702
Other
Sponsors
Affymax, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. Patient is informed of the investigational nature of this study and has given written, witnessed informed consent in accordance with institutional, local, and national guidelines b. Males or females = 18 years of age. Pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 4 weeks prior to study start, and must be willing to continue contraception until at least 4 weeks after the last dose of study drug c. Clinically stable on hemodialysis for = 3 months prior to study start d. Epoetin (alfa or beta) maintenance therapy, = 50 and = 200 U/kg/wk, at the same dosing frequency, continuously prescribed for 8 weeks prior to study start e. Three mid- or end-of-week Hgb values of = 10.0 and = 12.5 g/dL in the 4 weeks prior to study start, with = 1.2 g/dL difference between any of the three values f. One TSAT > 20% within 4 weeks prior to study start g. One ferritin level = 100 ng/mL within 4 weeks prior to study start h. One serum or red cell folate level = lower limit of normal during the 4 weeks prior to study start i. One vitamin B12 level = lower limit of normal during the 4 weeks prior to study start j. One C-reactive protein (CRP) level = 30 mg/L within 4 weeks prior to study start k. Urea clearance/volume (Kt/V) = 1.2 within 4 weeks prior to study start l. One white blood cell count (WBC) = 3.0 x 109/L within 4 weeks prior to study start m. One platelet count = 100 x 109/L and = 500 x 109/L within 4 weeks prior to study start Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a. Pregnant or breast-feeding patients b. Known intolerance to any erythropoiesis stimulating agent, parenteral iron supplementation or PEGylated molecules c. History of antibodies to any erythropoiesis stimulating agent or history of pure red cell aplasia (PRCA) d. Known bleeding or coagulation disorder e. Known hematologic disease (e.g., homozygous sickle-cell disease, thalassemia of all types, multiple myeloma, hemolytic anemia) f. Uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.) g. Known history of seizure disorder or received anti-epileptic medication within the previous 6 months h. Uncontrolled or symptomatic secondary hyperparathyroidism, per Investigator’s clinical judgment i. Poorly controlled hypertension within 4 weeks prior to study start, per Investigator’s clinical judgment j. Chronic congestive heart failure of New York Heart Association class III or IV k. High likelihood of early withdrawal or interruption of the study (e.g., myocardial infarction, severe or unstable coronary artery disease, stroke, respiratory, autoimmune, neuropsychiatric, or neurological abnormalities, liver disease including active hepatitis B or C, active HIV disease, or any other clinically significant medical diseases or conditions in the prior 6 months that may, in the Investigator’s opinion, interfere with safety, assessment, or follow-up of the patient) l. Evidence of malignancy within the past 5 years (except non-melanoma skin cancer which is not an exclusion criterion) m. Life expectancy < 12 months n. Temporary (untunneled) dialysis access catheter o. Anticipated elective surgery during the study period, that may be expected to lead to significant blood loss, including vascular access surgery such as an arteriovenous fistula or graft, or a scheduled kidney transplant p. RBC or whole blood transfusion within 12 weeks prior to study start q. Received antibiotics for systemic infection within 2 weeks prior to study start r. Previous exposure to any investigational agent within 6 weeks prior to study start, or planned receipt of an investigational agent, other than as specified by this protocol, during the study period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the dose ranges of AF37702 Injection, administered intravenously (IV) or subcutaneously (SC) using every-4-week (Q4W) or every-2-week (Q2W) dosing schedules that maintain hemoglobin (Hgb) within 1.0 g/dL below baseline to 1.5 g/dL above baseline, inclusive, in hemodialysis patients whose Hgb values were stable on Epoetin; Secondary Objective: The secondary objectives of the study are to: • Evaluate and compare the safety of AF37702 Injection administered by IV or SC injection using every-4-week (Q4W) or every-2-week (Q2W) dosing schedules; • Evaluate and compare the pharmacodynamics (PD) of AF37702 Injection administered by IV or SC injection using a Q4W or Q2W dosing schedule; • Evaluate and compare the pharmacokinetic (PK) profile of AF37702 Injection administered by IV or SC injection using a Q4W or Q2W dosing schedule in a subset of hemodialysis patients (i.e. evaluate PK parameters such as: Cmax, AUC0-t, AUC0-8, t½ß, Vd, Vss, and CL). ; Primary end point(s): • Hgb change from baseline to the average during weeks 21-28; • Average weekly Hgb (absolute value and change from baseline) throughout the trial; • Proportion of patients with Hgb within 1.0 g/dL below baseline to 1.5 g/dL above baseline, inclusive, during weeks 21-28 ; • Proportion of patients who maintain Hgb within the baseline range of 10.0 to 12.5 g/dL during Weeks 21-28; • Proportion of patients who maintain Hgb within 0.5 g/dL of the baseline Hgb range (i.e. 9.5 to 13.0 g/dL) during Weeks 21-28; • Frequency of red blood cell (RBC) or whole blood transfusions throughout the trial; • Number (%) of patients requiring dose adjustments throughout the trial; • Average dose of study drug (per 4-week | — |
Countries
United Kingdom
Outcome results
None listed