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

A Multicenter, Randomized, Open Label, Active Comparator Parallel Controlled Phase 2 Clinical Study on Intravenous Administration of rESP Injection for the Treatment of Anemia in Chronic Renal Failure Patients With Hemodialysis.

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

Study Overview

• Status: Unknown
• Conditions: Chronic Renal Failure With Hemodialysis
• Intervention / Treatment: Drug: Recombinant Human Erythropoiesis Injection (CHO cell); Drug: Recombinant Erythropoiesis Stimulating Protein Injection(CHO cell)

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 Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • The General Hospital of the People's Liberation Army
      • Contact: Peipei Liang, PHD
      • Principal Investigator: Xiangmei Chen, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group A; intravenous administration, maintaining the same dose and frequency administrated in the sceening period, for 32 weeks	Drug: Recombinant Human Erythropoiesis Injection (CHO cell); rHuEPO is a recombinant human erythropoietin with the same biological effects as natural erythropoietin; Other Names: rHuEPO
Experimental: Experimental group B; intravenous administration, 0.5μg/kg, once a week, for 32 weeks	Drug: Recombinant Erythropoiesis Stimulating Protein Injection(CHO cell); rESP is a high glucose medium and long-acting recombinant protein products, containing 165 amino acids by adding 3 glycosylation sites; Other Names: rESP
Experimental: Experimental group C; intravenous administration, 1μg/kg, once every two weeks, for 32 weeks	Drug: Recombinant Erythropoiesis Stimulating Protein Injection(CHO cell); rESP is a high glucose medium and long-acting recombinant protein products, containing 165 amino acids by adding 3 glycosylation sites; Other Names: rESP

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2019
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: May 10, 2019
• First Submitted That Met QC Criteria: May 13, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 9, 2020
• Last Update Submitted That Met QC Criteria: March 6, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: SYSS-SSS06-HD-II-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No