Renal Anemia in Non-dialysis Chronic Kidney Disease
Conditions
Keywords
Anemia
Brief summary
This was a multicenter, randomized, open label, non inferiority clinical study. It consisted of a 24-week treatment period (0-24 weeks) and a 24-week extension period (25-48 weeks). About 160 patients which had received Recombinant human erythropoietin (rHuEPO) or Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) treatment were randomized in a 1:1 ratio to receive Pegmolesatide with different administration regimens.
Detailed description
This was a multicenter, randomized, open label, non inferiority clinical study. It consisted of a 24-week treatment period (0-24 weeks) and a 24-week extension period (25-48 weeks). About 160 patients were randomized in a 1:1 ratio to Pegmolesatide optimize medication regimen group and Pegmolesatide standard medication regimen group. Patients in the investigational group received 2.0 mg (in patients weighing ≤60 kg) or 3.2 mg (in patients weighing \>60 kg) as the initial dose, the initial dose of the control group was 0.04mg/kg, then were adjusted for every 4 weeks based on Hb levels and its changes. The primary endpoint was the change in Hb levels from baseline in week 24.
Interventions
DRUGPegmolesatide
Pegmolesatide Injection: Specification 1mL: 4.0mg (National Medical Products Administration Approval No. H20230020), administered once every 4 weeks
Sponsors
The First Affiliated Hospital of Dalian Medical University
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria: 1. Aged ≥18 years and ≤80 years, regardless of gender; 2. Body weight ≥45 kg; Body Mass Index (BMI) ≥18.5 kg/m²; 3. Diagnosed with chronic kidney disease (CKD) complicated by renal anemia, with an estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m² before randomization (GFR estimation using the CKD-EPI formula); Undergoing continuous treatment with rHuEPO or HIF-PHI for ≥2 weeks before randomization; 4. Hemoglobin (Hb) level measured within 7 days before randomization ≥70 g/L and \< 110 g/L; 5. Understanding the study procedures and voluntarily signing the Informed Consent Form (ICF) *
Exclusion criteria
1. Known to have hematological disorders or other diseases that cause anemia other than chronic kidney disease (CKD), such as primary pure red cell aplasia (PRCA), homozygous sickle cell disease, thalassemia/Cooley's anemia, multiple myeloma, hemolytic anemia, and myelodysplastic syndrome, or malignant tumors; 2. Known to be allergic to iron agents or polyethylene glycol; 3. Received red blood cell or whole blood transfusion therapy within the three months prior to randomization; 4. Having received or planned to receive anabolic steroid (e.g., androgen) therapy within 12 weeks prior to randomization or during the study treatment period; 5. Poorly controlled blood pressure (specific criteria for determination are referenced in Appendix II); 6. C-reactive protein (CRP) ≥30 mg/L within 7 days prior to randomization; 7. Pregnant or breastfeeding women, women of childbearing age with a positive urine β-HCG test result prior to the study, or those planning to become pregnant during the study; 8. Assessed as having Class C liver function within 7 days prior to randomization (Child-Pugh classification, details in Appendix IV); 9. Assessed as having Class III or IV cardiac function within 28 days prior to randomization (details in Appendix III); 10. Subjects deemed by the investigator to have any other factors that make them unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of mean Hb levels from baseline in the standard medication regimen group and the optimized medication regimen group at week 24 of the treatment period. | the 24th week of treatment. | Baseline Hb was defined as the assessments of Hb during 3days prior to first dose of the study treatment. Mean Hb levels at week 24 of the treatment period (Hb at week 24) was defined as the mean of Hb at day 168±5 of the treatment period. Changes of mean Hb levels from baseline in the standard medication regimen group and the optimized medication regimen group at week 24 of the treatment period was calculated by subtracting the baseline Hb from Hb at week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median time for two groups of Hb values to reach the target (110-130g/L) for the first time | during the 48 weeks of treatment. | Median time for two groups of Hb values to reach the target (110-130g/L) for the first time. |
| The proportion of subjects with Hb average values ranging from 100-120 g/L and 110-130 g/L at each follow-up point during the treatment period in the two groups | During the 48-week period | The proportion of subjects with Hb average values ranging from 100-120 g/L and 110-130 g/L at each follow-up point during the treatment period in the two groups |
| Change of Hb from baseline at each follow-up point | during the 48 weeks of treatment. | Change of Hb from baseline at each follow-up point. |
| The absolute values of Hb levels at each follow-up point in the two groups during the treatment period | during the 48 weeks of treatment. | The absolute values of Hb levels at each follow-up point in the two groups during the treatment period |
| Change of red blood cell count from baseline at each follow-up point | during the 48 weeks of treatment. | Change of red blood cell count from baseline at each follow-up point. |
| Change of hematocrit from baseline at each follow-up point | during the 48 weeks of treatment. | Change of hematocrit from baseline at each follow-up point. |
| the fluctuation of Hb values between the two groups after 24 weeks (Hb variability) | after the 24 weeks of treatment. | It was defined as the coefficient of variation of Hb values after 24 weeks, which was calculated by dividing the SD (standard deviation) by the mean of Hb after the 24 weeks of treatment. |
| The average dose of the trial drug used between every two visits during the treatment period in the two groups | during the 48 weeks of treatment. | The average dose of the trial drug used between every two visits during the treatment period in the two groups |
| The average dosage of medication for subjects in both groups with mean Hb values in the range of 100-120 g/L and 110-130 g/L at each follow-up visit during the treatment period | During the 48-week period | The average dosage of medication for subjects in both groups with mean Hb values in the range of 100-120 g/L and 110-130 g/L at each follow-up visit during the treatment period |
| Cumulative number of dose adjustments for both groups of subjects in weeks 24 and 48 | the 24th and 48th week of treatment. | Cumulative number of dose adjustments for both groups of subjects in weeks 24 and 48. |
| The changes in patient-reported outcomes (PROs) from baseline at week 24 in the two groups | During the 24-week period | The changes in patient-reported outcomes (PROs) from baseline at week 24 in the two groups |
| The proportion of all-cause death events in the two groups at the end of follow-up | during the 48 weeks of treatment. | The proportion of all-cause death events in the two groups at the end of follow-up |
| The proportion of cardiovascular death events in the two groups at the end of follow-up | during the 48 weeks of treatment. | The proportion of cardiovascular death events in the two groups at the end of follow-up |
| The proportion of stroke and myocardial infarction events in the two groups at the end of follow-up | during the 48 weeks of treatment. | The proportion of stroke and myocardial infarction events in the two groups at the end of follow-up |
| The proportion of subjects entering the renal replacement therapy phase in the two groups at the end of follow-up | during the 48 weeks of treatment. | The proportion of subjects entering the renal replacement therapy phase in the two groups at the end of follow-up |
| Therapeutic response of populations with different baseline characteristics to pegmolesatide | at the week 24 of treatment. | Changes of mean Hb levels of populations with different baseline characteristics from baseline at week 24 of the treatment period. |
| The changes in carbamylated EPO levels and erythropoiesis (EPO) levels from baseline at week 24 in the two groups | During the 48-week period | The changes in carbamylated EPO levels and erythropoiesis (EPO) levels from baseline at week 24 in the two groups |
Countries
China
Contacts
CONTACTHongli Lin, M.D.
CONTACTJilin Chen, M.D.
PRINCIPAL_INVESTIGATORHongli Lin, M.D.
The First Affiliated Hospital of Dalian Medical University
Outcome results
None listed