Anemia, Chronic Kidney Disease (CKD)
Conditions
Keywords
erythropoietin alfa, CKD 5d
Brief summary
The purpose of this study is to show biosimilarity of HX575 epoetin alfa with the US licensed reference product Epogen®/Procrit® when applied subcutaneously. This study is intended to generate data supporting that the efficacy and safety under treatment with HX575 and Epogen®/Procrit® are comparable.
Detailed description
This is a randomized, double-blind, parallel-group, multicenter study to evaluate the efficacy and safety of HX575 epoetin alfa vs. US-licensed epoetin alfa (Epogen®/Procrit®) in the treatment of anemia associated with chronic kidney disease (CKD).
Interventions
DRUGHX575 epoetin alfa
Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL.
DRUGUS-licensed epoetin alfa
Solution for subcutaneous injection.
Sponsors
Sandoz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with end stage renal disease (stage CKD 5d), receiving stable subcutaneous maintenance therapy with Epogen® or Procrit® at least once per week * Mean hemoglobin level between 9.0 - 11.5 g/dL during the screening period * Adequate iron substitution
Exclusion criteria
* Contraindications for Erythropoiesis Stimulating Agent (ESA) therapy * History of Pure Red Cell Aplasia (PRCA), or anti-erythropoietin (EPO) antibodies * Known Human Immunodeficiency Virus (HIV) or Hepatitis B infection * Hepatitis C infection on an active treatment * Symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III and IV) * Unstable angina pectoris, or cardiac infarction during the last 6 months prior to randomization * Percutaneous coronary intervention, or coronary artery bypass grafting during the last 6 months prior to randomization * History of malignancy of any organ system * Systemic lupus erythematous * Immunocompromized patients Other In-/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Absolute Change in Hemoglobin Levels Between the Screening/Baseline Period (Week -4 to Day 1) and the Evaluation Period (Week 21-28) | Week -4 to Day1 and Week 21-28 | Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study . |
| Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28) | Week -4 to Day1 and Week 21-28 | Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Weekly Dose During Evaluation Period (Week 21-28) | Week 21-28 | Mean weekly study drug dose during evaluation period (Week 21-28) |
| Incidence of Antibody Formation Against Epoetin | 52 weeks | Number of patients with positive antidrug antibody (ADA) finding at any time during their treatment period. Count includes 2 patients (1 in each arm) that already had a positive ADA Baseline finding. ADA testing performed by by Radio-Immuno-Precipitation assay. No patient developed neutralizing antibodies. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HX575 Epoetin Alfa HX575, recombinant human epoetin alfa
HX575 epoetin alfa: Solution for subcutaneous injection. The drug is administered subcutaneously at least once per week over 52 weeks. The dose will be individually titrated to maintain hemoglobin levels between 10 to 11 g/dL. | 217 |
| US-licensed Epoetin Alfa US-licensed recombinant human epoetin alfa
US-licensed epoetin alfa: Solution for subcutaneous injection. | 218 |
| Total | 435 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 6 |
| Overall Study | Bindinging anti-EPO antibodies | 6 | 2 |
| Overall Study | Change in dialysis modality | 2 | 1 |
| Overall Study | Death | 5 | 8 |
| Overall Study | Kidney transplantation | 7 | 7 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliance | 2 | 1 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 6 | 7 |
| Overall Study | Withdrawal by Subject | 15 | 22 |
Baseline characteristics
| Characteristic | HX575 Epoetin Alfa | Total | US-licensed Epoetin Alfa |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 13.76 | 58.7 years STANDARD_DEVIATION 13.61 | 57.6 years STANDARD_DEVIATION 13.4 |
| BMI | 29.55 kg/m^2 STANDARD_DEVIATION 6.872 | 30.48 kg/m^2 STANDARD_DEVIATION 7.933 | 31.41 kg/m^2 STANDARD_DEVIATION 8.783 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 95 Participants | 188 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 122 Participants | 247 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 167.2 cm STANDARD_DEVIATION 10.17 | 166.6 cm STANDARD_DEVIATION 10.26 | 166.0 cm STANDARD_DEVIATION 10.33 |
| Method of dialysis at Baseline Hemodialysis | 192 Participants | 384 Participants | 192 Participants |
| Method of dialysis at Baseline Peritoneal dialysis | 25 Participants | 51 Participants | 26 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Amyloidosis | 1 Participants | 1 Participants | 0 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Chronic glomerulonephritis | 13 Participants | 29 Participants | 16 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Diabetes mellitus | 115 Participants | 237 Participants | 122 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Hypertension | 65 Participants | 117 Participants | 52 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Kidney abnormalities | 8 Participants | 19 Participants | 11 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Other | 3 Participants | 7 Participants | 4 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Polycystic kidney disease | 5 Participants | 9 Participants | 4 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Unknown | 3 Participants | 12 Participants | 9 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Urinary tract obstruction | 2 Participants | 2 Participants | 0 Participants |
| Primary cause of Chronic Kidney Disease (CKD) Vasculitis | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants | 16 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 19 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 57 Participants | 129 Participants | 72 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 139 Participants | 267 Participants | 128 Participants |
| Region of Enrollment United States | 217 participants | 435 participants | 218 participants |
| Sex: Female, Male Female | 82 Participants | 185 Participants | 103 Participants |
| Sex: Female, Male Male | 135 Participants | 250 Participants | 115 Participants |
| Time since start of dialysis | 36.11 months | 38.60 months | 41.08 months |
| Time since start of ESA therapy | 30.59 months | 32.95 months | 36.24 months |
| Type of last Erythropoiesis Stimulating Agent (ESA) therapy prior Epogen | 217 Participants | 432 Participants | 215 Participants |
| Type of last Erythropoiesis Stimulating Agent (ESA) therapy prior Procrit | 0 Participants | 3 Participants | 3 Participants |
| Weight | 82.8 kg STANDARD_DEVIATION 20.75 | 84.6 kg STANDARD_DEVIATION 22.66 | 86.5 kg STANDARD_DEVIATION 24.32 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 217 | 11 / 218 |
| other Total, other adverse events | 112 / 217 | 123 / 218 |
| serious Total, serious adverse events | 91 / 217 | 90 / 218 |
Outcome results
Primary
Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28)
Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study .
Time frame: Week -4 to Day1 and Week 21-28
Population: The intent-to-treat (ITT) population consists of all randomized patients who were exposed to treatment with study drug for at least four weeks and have at least one Hb value available at week 4 or later. Following the intent-to-treat principle, patients are analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HX575 Epoetin Alfa | Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28) | Baseline period | 10.53 g/dL | Standard Deviation 0.635 |
| HX575 Epoetin Alfa | Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28) | Evaluation period | 10.42 g/dL | Standard Deviation 0.826 |
| HX575 Epoetin Alfa | Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28) | Change from baseline period to evaluation period | -0.11 g/dL | Standard Deviation 1.011 |
| US-licensed Epoetin Alfa | Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28) | Baseline period | 10.50 g/dL | Standard Deviation 0.615 |
| US-licensed Epoetin Alfa | Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28) | Evaluation period | 10.51 g/dL | Standard Deviation 0.873 |
| US-licensed Epoetin Alfa | Change in Mean Hb Level Between Baseline (Week -4 to Day1) and Evaluation Period (Week 21-28) | Change from baseline period to evaluation period | 0.01 g/dL | Standard Deviation 0.953 |
Primary
Mean Absolute Change in Hemoglobin Levels Between the Screening/Baseline Period (Week -4 to Day 1) and the Evaluation Period (Week 21-28)
Response to epoetin alfa in anemic patients with chronic renal failure is manifested by increased hematocrit, hemoglobin, reduced transfusion requirements and increase in quality of life. Hemoglobin (laboratory haematology parameter) is the primary endpoint of the study .
Time frame: Week -4 to Day1 and Week 21-28
Population: The intent-to-treat (ITT) population consists of all randomized patients who were exposed to treatment with study drug for at least four weeks and have at least one Hb value available at week 4 or later. Following the intent-to-treat principle, patients are analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HX575 Epoetin Alfa | Mean Absolute Change in Hemoglobin Levels Between the Screening/Baseline Period (Week -4 to Day 1) and the Evaluation Period (Week 21-28) | -0.0960 g/dL | Standard Error 0.0575 |
| US-licensed Epoetin Alfa | Mean Absolute Change in Hemoglobin Levels Between the Screening/Baseline Period (Week -4 to Day 1) and the Evaluation Period (Week 21-28) | -0.0035 g/dL | Standard Error 0.0573 |
90% CI: [-0.2264, 0.0413]
Secondary
Incidence of Antibody Formation Against Epoetin
Number of patients with positive antidrug antibody (ADA) finding at any time during their treatment period. Count includes 2 patients (1 in each arm) that already had a positive ADA Baseline finding. ADA testing performed by by Radio-Immuno-Precipitation assay. No patient developed neutralizing antibodies.
Time frame: 52 weeks
Population: All patients treated with study drug with a post-baseline antibody assessment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HX575 Epoetin Alfa | Incidence of Antibody Formation Against Epoetin | 7 Participants |
| US-licensed Epoetin Alfa | Incidence of Antibody Formation Against Epoetin | 2 Participants |
Secondary
Mean Weekly Dose During Evaluation Period (Week 21-28)
Mean weekly study drug dose during evaluation period (Week 21-28)
Time frame: Week 21-28
Population: The intent-to-treat (ITT) population consists of all randomized patients who were exposed to treatment with study drug for at least four weeks and have at least one Hb value available at week 4 or later. Following the intent-to-treat principle, patients are analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HX575 Epoetin Alfa | Mean Weekly Dose During Evaluation Period (Week 21-28) | 5876.5 international units | Standard Deviation 5785.5 |
| US-licensed Epoetin Alfa | Mean Weekly Dose During Evaluation Period (Week 21-28) | 5804.0 international units | Standard Deviation 6343.7 |