Clinical trial NCT03950687: Study of rESP Injection for the Treatment of Anemia in Chronic Renal Failure Patients With Hemodialysis
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chronic Renal Failure With Hemodialysis
Lead sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.
Sponsor class: INDUSTRY
First posted: 2019-05-15
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary efficacy index :hemoglobin concentration
timeFrame: 25th-32nd week
Secondary outcomes:
measure: Secondary efficacy index:maintenance rate
timeFrame: 25th-32nd week
measure: Secondary efficacy index :proportion of subjects
timeFrame: for 32 weeks
measure: Secondary efficacy index: proportion of times
timeFrame: 25th-32nd week
measure: Secondary efficacy index : average weekly dose
timeFrame: 25th-32nd week
measure: Secondary efficacy index: EPO dose conversion coefficient of rESP
timeFrame: for 32 weeks
measure: Secondary efficacy index : mean reticulocyte count
timeFrame: 25th-32nd week
measure: Secondary efficacy index : mean red blood cell count
timeFrame: 25th-32nd week
measure: Safety indicator: adverse events
timeFrame: for 32 weeks
measure: Safety indicator: number of dose adjustments
timeFrame: for 32 weeks
measure: Safety indicator: the ratio of subjects who are adjusted
timeFrame: for 32 weeks
measure: Safety indicator: incidence of erythropoietin (EPO) antibodies and anti-rESP antibodies
timeFrame: for 32 weeks
measure: Maximum Plasma Concentration (Cmax)
timeFrame: for 32 weeks
measure: Area Under the Curve (AUC)
timeFrame: for 32 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: The general hospital of the people's liberation army
state: Beijing
Study officials:
References: