Pegmolesatide Treatment for Anemia in Patients Undergoing Long-term Dialysis (PANGU-stepup)

Chinese PLA General Hospital (301 Hospital)

Status and phase: Begins enrollment this month; Phase 4

Conditions: Renal Anaemia; Renal Anemia of Chronic Kidney Disease; Renal Anemia, Chronic; Chronic Kidney Disease 5D; Dialysis; Complications

Treatments: Drug: The Pegmolesatide Monotherapy Group (Experimental group); Drug: The Pegmolesatide and Roxadustat Combination Therapy Group (Exploratory Group); Drug: The rHuEPO Monotherapy Group (Control Group)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07045155

HS-20039-404

Details and patient eligibility

About

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.

Full description

title： Pegmolesatide for anemia treatment：investigation upgrade therapy in rhuEPO patients undergoing dialysis: A Prospective, Multicenter, Parallel-Group, Controlled, Open-Label Study（PANGU-upgrade） Introduction: Anemia is a primary complication of chronic kidney disease (CKD). In recent years, there have been many effective strategies for treating anemia in CKD, including erythropoiesis-stimulating agents (ESAs), hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), and erythropoietin (EPO) mimetic peptides (EMPs) such as Pegmolesatide. This study aims to explore the efficacy and safety of switching patients with anemia of dialysis-dependent chronic kidney disease (DD-CKD), whose hemoglobin (Hb) levels have not reached the target after treatment with recombinant human erythropoietin (rHuEPO), to treatment with pegmolesatide.

Methods:

This study is designed as a prospective, multicenter, parallel-controlled, open-label trial. It plans to enroll 240 participants with anemia of dialysis-dependent chronic kidney disease (DD-CKD) who have been receiving recombinant human erythropoietin (rHuEPO) treatment for at least 4 weeks, with hemoglobin (Hb) levels of ≥70 g/L and <110 g/L. Participants will be randomly assigned in a 1:1:1 ratio to the experimental group, the control group, and the exploratory group. The study will consist of a 24-week treatment and observation period, divided into three phases: the screening period (Day -28 to Day -1), the treatment period (Week 0 to Week 16), and the extension period (Week 17 to Week 24).

This study plans to recruit participants from 20 large tertiary hospitals across multiple provinces and cities in China. The primary endpoint of the study is the change in mean hemoglobin (Hb) levels from baseline at weeks 12 to 16 of treatment in the three groups. The study will observe and evaluate the efficacy and safety of switching patients with anemia of dialysis-dependent chronic kidney disease (DD-CKD) who have not achieved target Hb levels after treatment with recombinant human erythropoietin (rHuEPO) to treatment with pegmolesatide alone or pegmolesatide in combination with roxadustat.

Enrollment: 240 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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. Diagnosed with chronic kidney disease (CKD) stage 5 for ≥12 months, and has been on hemodialysis or peritoneal dialysis for ≥3 months prior to enrollment.
4. Has been receiving rHuEPO treatment for at least 4 weeks before randomization, with an average weekly dose of >6000 IU over the past 4 weeks (calculated as: total rHuEPO dose over the past 4 weeks/4), and the interval between the last dose and randomization is no less than 5 half-lives of rHuEPO (half-life of recombinant human erythropoietin-α: 19 hours for subcutaneous injection, 7 hours for intravenous injection).
5. During the screening period, the most recent two laboratory hemoglobin (Hb) values (with at least 6 days apart) are ≥70 g/L and <110 g/L, and the absolute difference between the two Hb values is ≤10 g/L.
6. For hemodialysis patients, serum ferritin level is ≥200 μg/L; for peritoneal dialysis patients, serum ferritin level is ≥100 μg/L. The investigator determines that the patient will not require kidney transplantation as an alternative treatment throughout the trial.
7. Understands the study procedures and voluntarily provides written informed consent (ICF).

Exclusion criteria

1. Known to have active malignancy, autoimmune diseases, 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. History of stroke, transient ischemic attack, myocardial infarction, thromboembolic events (deep vein thrombosis), pulmonary embolism, or other severe cardiopulmonary diseases within the past 6 months.
3. Use of immunosuppressive agents or corticosteroids orally or intravenously, or other medications that may affect the treatment of renal anemia within 12 weeks before randomization.
4. Receipt of red blood cell or whole blood transfusion within 12 weeks before the trial.
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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 3 patient groups

The Pegmolesatide Monotherapy Group (Experimental Group)

Experimental group

Description:

The Pegmolesatide Monotherapy Group (Experimental Group) will receive Pegmolesatide treatment throughout the entire 24-week period.

Treatment:

Drug: The Pegmolesatide Monotherapy Group (Experimental group)

The rHuEPO Monotherapy Group (Control Group)

Active Comparator group

Description:

The rHuEPO Monotherapy Group (Control Group) will be treated with rHuEPO for the first 16 weeks and then switch to Pegmolesatide treatment for the subsequent 8 weeks.

Treatment:

Drug: The rHuEPO Monotherapy Group (Control Group)

The Pegmolesatide and Roxadustat Combination Therapy Group (Exploratory Group)

Active Comparator group

Description:

The Pegmolesatide and Roxadustat Combination Therapy Group (Exploratory Group) will receive a combination of Pegmolesatide and roxadustat throughout the entire 24-week treatment period.

Treatment:

Drug: The Pegmolesatide and Roxadustat Combination Therapy Group (Exploratory Group)