Pegmolesatide for Anemia Treatment：Investigation Upgrade Therapy in rhuEPO Patients Undergoing Dialysis: A Prospective, Multicenter, Parallel-Group, Controlled, Open-Label Study（PANGU-stepup）
Trial ID: NCT07045155
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: PHASE4
Start date: 2025-08-01
Completion date: 2028-12-30
Sponsor: Chinese PLA General Hospital
Collaborators: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Conditions: Dialysis; Complications; Chronic Kidney Disease 5D; Renal Anemia of Chronic Kidney Disease; Renal Anaemia; Renal Anemia, Chronic
Interventions: The rHuEPO Monotherapy Group (Control Group); The Pegmolesatide and Roxadustat Combination Therapy Group (Exploratory Group); The Pegmolesatide Monotherapy Group (Experimental group)
Locations: Chinese PLA General Hospital
Countries: China
Enrollment: 240
Age range: 18 Years - 80 Years
Sex: ALL

Summary:
This study is a prospective, multicenter, parallel-controlled, open-label clinical trial, planned to be conducted across multiple research centers in various provinces and cities in China.

It will enroll 240 dialysis-dependent chronic kidney disease (DD-CKD) patients with anemia who have been receiving rHuEPO treatment for at least 4 weeks, with hemoglobin (Hb) levels of ≥70 g/L and \<110 g/L. After enrollment, participants will be randomly assigned in a 1:1:1 ratio to the experimental group, control group, and exploratory group. The study will involve a 24-week treatment and observation period, divided into three phases: a screening period (Day -28 to Day -1), a treatment period (Week 0 to Week 16), and an extension period (Week 17 to Week 24).

The primary objective is to assess the impact of the three treatment regimens on the hemoglobin levels of patients with DD-CKD anemia.

Eligibility criteria:
Inclusion Criteria:

1. Aged ≥18 years and ≤80 years, with no restrictions on gender.
2. Body weight ≥40 kg and body mass index (BMI) ≥18 kg/m².
3. Subjects who have received hemodialysis or peritoneal dialysis for ≥3 months prior to enrollment;
4. Subjects who have been receiving erythropoiesis-stimulating agents (ESAs) for ≥4 weeks prior to randomization, with an average weekly dose \>6000 IU in the last 4 weeks (equivalent dose converted to short-acting EPO \>6000 IU, calculated as the total amount of short-acting EPO used in the last 4 weeks divided by 4);
5. The most recent Hb value during the screening period and the average Hb value between screening and baseline visits must be ≥70 to \<110 g/L;
6. Hemodialysis patients with serum ferritin levels ≥200 μg/L; peritoneal dialysis patients with serum ferritin levels ≥100 μg/L, and the investigator determines that renal transplant is not required during the trial;
7. Understanding the study procedures and voluntarily signing the Informed Consent Form (ICF).

Exclusion Criteria:

1. Known to have active malignancy, polycystic kidney disease, hematologic disorders (including congenital and acquired anemias such as thalassemia, Fanconi anemia, pure red cell aplasia, myelodysplastic syndromes, hemolytic anemia, and coagulation disorders), or other causes of anemia (such as gastrointestinal bleeding or hookworm disease);
2. Known to have experienced stroke, transient ischemic attack, myocardial infarction, thromboembolic events (deep vein thrombosis), pulmonary embolism, or other serious cardiopulmonary diseases within the past 6 months;
3. Received anabolic steroid (e.g., androgen) therapy within 12 weeks prior to randomization;
4. Known to have received red blood cell or whole blood transfusion within 12 weeks prior to the study.
5. History of significant infection within 4 weeks before randomization as determined by the investigator.
6. Confirmed blood pressure measurements at rest and in a conscious state using standard measurement methods, with at least three non-consecutive day readings reaching or exceeding systolic blood pressure (SBP) ≥180 mmHg and/or diastolic blood pressure (DBP) ≥110 mmHg within 4 weeks before enrollment, or changes in antihypertensive medication treatment. The primary basis for judgment is clinic-measured blood pressure values, but "white coat hypertension" should be excluded.
7. Known allergy to iron agents or polyethylene glycol.
8. Pregnant or breastfeeding women, women of childbearing age with a positive blood β-HCG test result before the trial, or those planning to become pregnant during the study period.
9. Scheduled for elective surgery during the trial period.
10. Presence of any other factors that the investigator deems unsuitable for participation in this trial.

Outcomes:
The change in mean hemoglobin (Hb) levels from baseline at weeks 12 to 16 of treatment in the three groups.