Study of rESP Injection for the Treatment of Anemia in Chronic Renal Failure Patients With Hemodialysis

Phase 2

• Conditions: Chronic Renal Failure With Hemodialysis
• Interventions: Drug: Recombinant Erythropoiesis Stimulating Protein Injection(CHO cell); Drug: Recombinant Human Erythropoiesis Injection (CHO cell)

• Registration Number: NCT03950687
• Lead Sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.

Brief Summary

A phase 2, randomized, open label, active comparator parallel controlled study to explore the dosage regiment of rESP, and evaluate its efficacy, safety and pharmacokinetic characteristics in the treatment of anemia in chronic renal failure patients with hemodialysis

Detailed Description

In this phase 2, open label, active comparator parallel controlled study, patients were randomly assigned to three study groups: one active comparator control group (rHu EPO, maintaining the same dose and frequency administrated in the sceening period ), and two experimental groups (0.5μg/kg ,once a week; 1.0μg/kg , once every two weeks). All the patients were administered intravenously for 32 weeks and were evaluated the efficacy, safety and pharmacokinetic characteristics. During the whole study period, dosage adjustment was not allowed in the first 4 weeks, while in the remaining trial period dosage adjustment was allowed once every two weeks if necessary.

Study Timeline

• Study First Submitted: 2019-05-10
• Study First Submitted QC: 2019-05-13
• Study First Posted: 2019-05-15
• Study Start: 2019-06-24
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-06
• Last Update Posted: 2020-03-09
• Primary Completion: 2020-06-30
• Study Completion: 2020-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Patients with chronic renal failure are undergoing maintenance hemodialysis for at least 3 months and at least 2 times a week;
2. 18 years old ≤ age ≤ 75 years old, gender is not limited;
3. Being treated with rHuEPO for at least 12 weeks, the average concentration of hemoglobin in the screening period is in the range of 100~120 g/L (including both ends), and the difference is less than 10g/L;
4. Evaluation of iron status within 4 weeks, transferrin saturation (TSAT) ≥ 20% and serum ferritin (SF) ≥ 200 μg / L;
5. Subjects agree to use reliable contraceptives by themselves and their spouses from the screening period to within 3 months after the end of the study;
6. Volunteer as a subject and sign an informed consent form.

Exclusion Criteria

1. Patients who have received or plan to undergo a kidney transplant during the study period, or who plan to undergo other surgery during the study;

2. Except of renal anemia, there are other diseases that cause chronic anemia (such as sickle cell anemia, myelodysplastic syndrome, hematological malignancies, myeloma, hemolytic anemia, pure red blood cell aplastic anemia), blood systemic disease or coagulopathy;

3. There are acute or chronic blood loss within the past 3 months, such as gastrointestinal bleeding;

4. The following circumstances (including but not limited to), the investigators evaluated that it is not suitable for enrollment:

   • Kt/V<1.2 or URR<65%;
   • Abnormal liver function (the aspartate aminotransferase or alanine aminotransferase is greater than 3 times the upper limit of normal);
   • Patients who were positive for anti-HIV, anti-HCV, and Treponema pallidum antibodies;

5. Patiernts who was suffering from severe secondary hyperparathyroidism (sustained blood iPTH/PTH >1000 ng/L);

6. Patiernts who was suffering from malignant hypertension or poor control of blood pressure (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg);

7. Patients with previous thromboembolic disease (excluding luminal infarction), history of severe hematopoietic system, and high clotting tendency;

8. Patiernts with severe cardiovascular and cerebrovascular disease, severe or unstable coronary artery disease, heart failure (NYHA class III or IV), temporary vascular access, or myocardial infarction or stroke within 3 months;

9. Patients with malignant tumors (excluding non-melanoma skin cancer or excised carcinoma in situ);

10. Patients with a history of severe allergies (including drug allergies), allergic to erythropoietin, or allergic to any component of the test drug (such as human serum albumin);

11. The infection is being treated with systemic antibiotics;

12. Those who have received androgen therapy or who have received blood transfusion therapy within the past 8 weeks;

13. 5 months as a subject to participate in other new drug clinical trials or to the group when the withdrawal time is shorter than the five half-life of the test drug (whichever is the longest of the two);

14. All epilepsy or epilepsy history except of childhood febrile seizures, post-traumatic or abstinence single seizures;

15. Pregnant women and lactating women;

16. Alcohol, drug or drug addicts;

17. Other factors investigators believe that they may affect the efficacy judgment or is not suitable for participation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group B	Recombinant Erythropoiesis Stimulating Protein Injection(CHO cell)	intravenous administration, 0.5μg/kg, once a week, for 32 weeks
Control group A	Recombinant Human Erythropoiesis Injection (CHO cell)	intravenous administration, maintaining the same dose and frequency administrated in the sceening period, for 32 weeks
Experimental group C	Recombinant Erythropoiesis Stimulating Protein Injection(CHO cell)	intravenous administration, 1μg/kg, once every two weeks, for 32 weeks

Primary Outcome Measures

Name	Time	Method
Primary efficacy index :hemoglobin concentration	25th-32nd week	the amount of change in mean Hb concentration compared with baseline Hb concentration during the evaluation period (25th-32nd week)

Secondary Outcome Measures

Name	Time	Method
Secondary efficacy index: proportion of times	25th-32nd week	the proportion of times the measured Hb concentration remains within the target range during the subject evaluation period
Safety indicator: adverse events	for 32 weeks	the type, proportion and severity of adverse events
Safety indicator: the ratio of subjects who are adjusted	for 32 weeks	the ratio of subjects who are adjusted during the treatment and evaluation period
Secondary efficacy index:maintenance rate	25th-32nd week	the proportion of subjects whose average Hb concentration remained within the target range during the evaluation period
Secondary efficacy index : average weekly dose	25th-32nd week	the average weekly dose of the drug during the evaluation period (normalized by body weight)
Secondary efficacy index :proportion of subjects	for 32 weeks	the proportion of subjects whose range of dose adjustments decreased or increased by 25% still did not reach 100-120 g/L (both ends)
Secondary efficacy index: EPO dose conversion coefficient of rESP	for 32 weeks	the EPO dose conversion coefficient of rESP (the average weekly dose of rESP during the screening period) and the dose correlation
Secondary efficacy index : mean red blood cell count	25th-32nd week	changes in mean values of red blood cell count compared to baseline values during the evaluation period
Safety indicator: number of dose adjustments	for 32 weeks	the number of dose adjustments used by the subject during the treatment and evaluation period
Area Under the Curve (AUC)	for 32 weeks	the AUC of rESP in patients with long-term medication.
Secondary efficacy index : mean reticulocyte count	25th-32nd week	changes in mean values of reticulocyte compared to baseline values during the evaluation period.
Safety indicator: incidence of erythropoietin (EPO) antibodies and anti-rESP antibodies	for 32 weeks	incidence of erythropoietin (EPO) antibodies and anti-rESP antibodies
Maximum Plasma Concentration (Cmax)	for 32 weeks	the Cmax of rESP in patients with long-term medication.

Trial Locations

Locations (1)

The general hospital of the people's liberation army; 🇨🇳 Beijing, Beijing, China