Anemia, Chronic Renal Insufficiency
Conditions
Keywords
Treatment, associated, with CRI
Brief summary
This is a randomized, controlled, double-blind, multicenter multinational safety study involving about 300 predialysis patients aged 18 years or above suffering from anemia. Symptomatic anemia will be corrected by s.c. application of EPO HEXAL or ERYPO® in order to achieve a hemoglobin target range of 10.0 -12.0 g/dL.
Interventions
Solution for injection (s.c.)
DRUGERYPO
Solution for injection (s.c.)
Sponsors
Sandoz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Known chronic renal insufficiency of at least 4 weeks duration; CKD stage at least 3 or higher * Male and female patients, age: \>=18 * Patients who are naïve to ESA treatment or previously ESA treated after 3 months of ESA-free period (i.v. or s.c.) * Patients with symptomatic anemia, defined as Hb level below 11.0 g/dL and not lower than or equal to 7.5 g/dL on at least 2 visits during the screening period * Adequate iron status, serum ferritin \>= 100 µg/L or transferrin saturation \>= 20% * Ability to follow study instructions and likely to complete all required visits and compliant with subcutaneous administration * Written informed consent of the patient.
Exclusion criteria
* Anemia of non-renal causes * Therapy with immunosuppressants (other than corticosteroids for chronic treatment) within 3 months before screening and during the study for patients with renal allograft in place or other chronic conditions (e.g. lupus erythematosus, rheumatic arthritis) * Patients previously treated with chronic dialysis within the last 6 months (exception: one session of acute dialysis) * Patients with acute deterioration of renal function during the screening phase according to the investigator's judgment * Patients receiving any RBC/whole blood transfusion during the screening period * Primary hematological disorder (e.g. myeloma, myelodysplastic syndrome, sickle cell anemia, hematological malignancy, hemolytic anemia) * Evidence of uncontrolled diabetes mellitus (HbA1c \> 10 % at visit -2) * Evidence of severe hepatic dysfunction (e.g. ALT and/or AST above 2x upper limit of normal range; or gamma-GT above 3x upper limit of normal range) * Clinical evidence of current uncontrolled or symptomatic hyperparathyroidism, defined as parathyroid hormone \> 500 ng/L at visit -2. * Uncontrolled hypertension, defined as a systolic blood pressure of \>= 160 mmHg and a diastolic blood pressure measurement \>= 100 mmHg (average of two values with at least one day between measurements) * Congestive heart failure and/or angina pectoris \[New York Heart Association (NYHA) class III and IV\] * History of stroke or myocardial infarction during the last 6 months prior to visit -2 * Ongoing treatment with phenprocoumon or other cumarin derivates * Thrombocytopenia (platelet count \<100.000/µL) or leucopenia (white blood cell count \< 2.000/µL) * Gastrointestinal bleeding within the last 6 months prior to visit -2 or hemolysis * Evidence of acute or chronic infection by a C-reactive protein value of \> 30 mg/L * Suspicion or known PRCA (pure red cell aplasia) * Previously diagnosed HIV or acute hepatitis infection * History of epilepsy or epileptic seizures or treatment for epilepsy within the past 6 months prior to screening * Planned major surgery (with expected high blood loss) during the next 3 months or major surgery within the previous 3 months (except laser photocoagulation, access surgery) * Clinical evidence of active malignant diseases within the last 5 years (except non-melanoma skin cancer) * Pregnancy, breastfeeding women or women not using a highly effective birth control method (e.g. implants, injectables, combined oral contraceptives, IUD, sexual abstinence, vasectomised partner) * Known history of severe drug related allergies (e.g. anaphylactic shock) * Known allergy to one of the ingredients of the test product or hypersensitivity to mammalian-derived products * Known or suspicion of any non-compliance with respect to subcutaneous treatment * Simultaneous participation in another clinical study or participation in a study in the month preceding visit-2 or previously randomized in this study * Participation in another ESA study in the 3 months preceding visit -2 * Any other condition which at the investigator's discretion may put the patient at risk or which may confound the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin Level | 13 weeks | Mean absolute change in hemoglobin (baseline to end of study week 13) |
| Weekly Epoetin Dose | weeks 11-13 | Mean weekly epoetin dose \[IU/kg\] in study weeks 11-13 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity | 13 weeks | Number of participants with antibody formation against Epoetin during treatment period (safety set) |
Countries
Austria, Bulgaria, Czechia, France, Germany, India, Poland, Romania, Russia, Slovakia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatmen HX575 EPO HEXAL HX575 recombinant human erythropoietin alfa: Solution for injection (s.c.) | 174 |
| Treatment ERYPO ERYPO: Solution for injection (s.c.) | 163 |
| Total | 337 |
Baseline characteristics
| Characteristic | Treatment ERYPO | Total | Treatmen HX575 EPO HEXAL |
|---|---|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 15 | 64.5 years STANDARD_DEVIATION 14.7 | 64.1 years STANDARD_DEVIATION 14.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 155 Participants | 322 Participants | 167 Participants |
| Region of Enrollment Austria | 1 participants | 5 participants | 4 participants |
| Region of Enrollment Bulgaria | 4 participants | 8 participants | 4 participants |
| Region of Enrollment Czech Republic | 19 participants | 41 participants | 22 participants |
| Region of Enrollment France | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Germany | 39 participants | 84 participants | 45 participants |
| Region of Enrollment India | 6 participants | 12 participants | 6 participants |
| Region of Enrollment Poland | 14 participants | 27 participants | 13 participants |
| Region of Enrollment Romania | 52 participants | 99 participants | 47 participants |
| Region of Enrollment Russian Federation | 24 participants | 53 participants | 29 participants |
| Region of Enrollment Slovakia | 3 participants | 7 participants | 4 participants |
| Sex: Female, Male Female | 98 Participants | 195 Participants | 97 Participants |
| Sex: Female, Male Male | 65 Participants | 142 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 174 | 14 / 163 | 2 / 151 | 1 / 119 |
| other Total, other adverse events | 137 / 174 | 132 / 163 | 87 / 151 | 58 / 119 |
| serious Total, serious adverse events | 50 / 174 | 70 / 163 | 22 / 151 | 24 / 119 |
Outcome results
Primary
Change in Hemoglobin Level
Mean absolute change in hemoglobin (baseline to end of study week 13)
Time frame: 13 weeks
Population: Full analysis set required: all randomized patients who received at least one dose of the study medication and for whom at least one Hb value after study day 27 was available. 3 out of 174 patients started in EPO HEXAL group and 6 out of 163 patients started in ERYPO group had no Hb values after study day 27 so they were excluded from analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HX575, EPO HEXAL | Change in Hemoglobin Level | 2.2 g/dL | Standard Deviation 1 |
| ERYPO | Change in Hemoglobin Level | 2.1 g/dL | Standard Deviation 1.2 |
Primary
Weekly Epoetin Dose
Mean weekly epoetin dose \[IU/kg\] in study weeks 11-13
Time frame: weeks 11-13
Population: Full analysis set required: all randomized patients who received at least one dose of the study medication and for whom at least one Hb value after study day 27 was available. 3 out of 174 patients started in EPO HEXAL group and 6 out of 163 patients started in ERYPO group had no Hb values after study day 27 so they were excluded from analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HX575, EPO HEXAL | Weekly Epoetin Dose | 55.1 IU/kg | Standard Deviation 41.9 |
| ERYPO | Weekly Epoetin Dose | 57.9 IU/kg | Standard Deviation 46.6 |
Secondary
Immunogenicity
Number of participants with antibody formation against Epoetin during treatment period (safety set)
Time frame: 13 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HX575, EPO HEXAL | Immunogenicity | 5 participants |
| ERYPO | Immunogenicity | 2 participants |