Chronic Kidney Diseases
Conditions
Brief summary
The purpose of this study is to evaluate the effecacy and safety of dialysis centers switching its dialysis patients from using recombinant human erythropoietin injection (CHO Cell) (ESPO) to Pegol-Sihematide injection on hemoglobin levels and other parameters.
Detailed description
This is a phase 3, randomized, multicenter, open-label, active-controlled, non-inferiority trial to evaluate the efficacy and safety of from ESPO to monthly Pegol-Sihematide injection for the treatment of anemia in participants with chronic kidney disease（CKD）, who are on maintenance dialysis. Study included a period of 4 weeks for screening, 8 weeks for baseline, 16 weeks for dose adjustment, 8 weeks for evaluation, and 28 weeks for extensional treatment period. All patients who passed the screening were received ESPO in baseline period, then, eligible patients were centrally allocated in a 2:1 ratio to receive Pegol-Sihematide or ESPO. Doses of both drugs were adjusted to achieve and maintain hemoglobin levels between 10.0 and 12.0 g per deciliter for 52 weeks or more. The primary efficacy end point was the mean change from the baseline hemoglobin level to the mean level during the evaluation period; non-inferiority was established if the lower limit of the two-sided 95% confidence interval was -1.0 g per deciliter or higher. Cardiovascular safety was evaluated on the basis of an adjudicated composite end point.
Interventions
DRUGPegol-Sihematide
Participants received Pegol-Sihematide by subcutaneous injection once every 4 weeks ; the dose was adjusted throughout the study to maintain a hemoglobin target range of 10.0-12.0 grams per deciliter (g/dL).
DRUGESPO
Participants received ESPO by subcutaneous injection or subcutaneous injection weekly. The dose was adjusted throughout the study to maintain a hemoglobin target range of 10.0-12.0 g/dL.
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must meet all of the following inclusion criteria to be eligible for participation in this study: 1. Males or females ≥18 and ≤70 years of age, weight ≥ 45 kilograms (kg). 2. Females of child-bearing potential who are sexually active had to be willing to practice a highly effective method of birth control for at least 4 weeks prior to randomization, and had to be willing to continue contraception until at least 4 weeks after the last dose of study treatment. 3. Participants with chronic renal failure on dialysis（hemodialysis/ peritoneal dialysis） for ≥ 3 months prior to randomization，and that the frequency of dialysis was stable and no change in dialysis pattern was observed during the trial. 4. On ESAs treatment for ≥8 weeks prior to screening stage with stable doses and the average doses ≤ 10000 IU/week. And two consecutive hemoglobin values ≥10.0 g/dL and ≤12.0 g/dL within 4 weeks prior to randomization. 5. At least one transferrin saturation (TSAT) ≥ 20% and one serum ferritin (SF) level ≥ 100 ng/ml within 4 weeks prior to randomization. At least one serum folate level and vitamin B12 level ≥ lower limit of normal during the 4 weeks prior to randomization. 6. Patient was informed of the investigational nature of the study and had given written, informed consent in accordance with institutional, local, and national guidelines.
Exclusion criteria
* Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The mean change from the baseline hemoglobin level to the mean level during the evaluation period | Week 17-24 | The primary efficacy end point is the mean change from the baseline hemoglobin level to the mean level during the evaluation period. The baseline hemoglobin value is defined as the mean of three hemoglobin values: the 4 weeks and 2 weeks recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the evaluation period was calculated as the mean of all available hemoglobin values during that period. Hemoglobin measurements will be performed at baseline and thereafter every 2 weeks (for the dose adjustment and the evaluation periods) or every 4 weeks (for the extensional treatment period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Dose of Participants With Hemoglobin Within ±1.0 g/dL of Baseline during the Evaluation Period | Week 17-24 | Mean dose was calculated at least 3 times from measurements taken during the Evaluation Period (Week 17 to Week 24). |
| Proportion of Patients Whose Hemoglobin Within ±1.0 g/dL of Baseline during the Evaluation Period | Week 17-24 | The hemoglobin value within ±1.0 g/dL of baseline is defined as the difference between the hemoglobin value and the baseline value in the 4 tests in the Evaluation Period was at least 3 times between 1.0g /dL. The Evaluation Period is defined as study weeks 17 through 24. |
| Percentage of Participants With Hemoglobin Within the Target Range of 10.0 to 12.0 g/dL During the Evaluation Period | Week 17-24 | The hemoglobin value within the target range of 10.0 to 12.0 g/dL during the evaluation period is defined as HGB values were between 10.0 and 12.0 g/dL in at least 3 of the 4 tests in the efficacy evaluation period. |
| Average Hemoglobin, RBC, hematokrit and reticulocytes change from baseline | Week 0-52 | The baseline hemoglobin value is defined as the mean of three hemoglobin values: the 4 weeks and 2 weeks recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcome Measures: antibody | Week 17-24 | The incidence of patients with antibody to Pegol-Sihematide. |
| Safety Outcome Measures: composite safety endpoint(CSE) | Week 0-52 | The incidence of patients with risk cardiovascular events, The CSE consisted of five events: death, stroke, myocardial infarction, and serious adverse events of congestive heart failure and unstable angina. An independent Clinical Endpoint Committee (CEC) was used to provide blinded adjudication of potential CSE events. |
| Safety Outcome Measures: adverse events | Week 0-52 | The incidence of patients who reported serious adverse events (SAE) |
Countries
China
Outcome results
None listed