A Study of Pegmolesatide of in Dialysis Chronic Kidney Disease (CKD) Patients With Anemia Treated With Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI)

Efficacy and Safety of Pegmolesatide in Dialysis Chronic Kidney Disease (CKD) Patients With Anemia Treated With Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI): a Multi-center, Prospective, Open-label, Randomized Parallel Controlled Trial

For patients with renal anemia treated with hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), there is a clinical need of switching to long-acting and safe medications.

Pegmolesatide, a polyethylene glycol (PEG)-conjugated erythropoiesis-stimulating peptide, is a long-acting erythropoiesis-stimulating agent (ESA) with sustained activity. It was approved for marketing by the National Medical Products Administration (NMPA) in June 2023. Phase III clinical trials have demonstrated its efficacy and safety in dialysis patients with renal anemia who were previously treated with recombinant human erythropoietin (rHuEPO). However, there are currently no data regarding the efficacy and safety of switching from HIF-PHIs to pegmolesatide, and there is a lack of standard for the dose conversion.

This study is a multi-center, prospective, open-label, randomized parallel-controlled clinical trial, planning to enroll 96 patients.

All enrolled patients will receive 12 weeks of treatment and be followed up for 16 weeks.

Study Overview

• Status: Recruiting
• Conditions: Renal Anemia of Chronic Kidney Disease
• Intervention / Treatment: Drug: Pegmolesatide 2mg SC; Drug: Pegmolesatide 4mg SC; Drug: Pegmolesatide 6mg SC

Detailed Description

For patients with renal anemia treated with HIF-PHIs, there is a clinical need of switching to long-acting and safe medications.

Pegmolesatide, a polyethylene glycol (PEG)-conjugated erythropoiesis-stimulating peptide, is a long-acting erythropoiesis-stimulating agent (ESA) with sustained activity. It was approved for marketing by the National Medical Products Administration (NMPA) in June 2023. Phase III clinical trials have demonstrated its efficacy and safety in dialysis patients with renal anemia who were previously treated with recombinant human erythropoietin (rHuEPO). However, there are currently no data regarding the efficacy and safety of switching from HIF-PHIs to pegmolesatide, and there is a lack of standard for the dose conversion.

This study is a multi-center, prospective, open-label, randomized parallel-controlled clinical trial, planning to enroll 96 patients.

Based on the weekly dose of Roxadustat before randomization, patients are divided into two cohorts: the low-dose Roxadustat cohort (weekly dose ≤210 mg) and the high-dose Roxadustat cohort (weekly dose >210 mg and ≤360 mg), with 48 patients in each cohort. Each cohort is stratified by hemoglobin (HB) level, with a 1:1 ratio for HB <10.0 g/dl and HB ≥10.0 g/dl, meaning that there are 24 patients in both cohorts.

Within each cohort, patients are randomly assigned to 2 groups at a 1:1 ratio based on the initial treatment dose of pegmolesatide. Specifically, the patients in low-dose Roxadustat cohort are randomized into the Pegmolesatide initial dose 2 mg group or 4 mg group; the patients in high-dose Roxadustat cohort are randomized into the Pegmolesatide initial dose 4 mg group or 6 mg group, with 24 patients in each group entering the trial period. Pegmolesatide is administered subcutaneously once every 4 weeks, and the dosage is adjusted according to the drug's instructions for use. All enrolled patients will receive 12 weeks of treatment and be followed up for 16 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xueqing Yu; Phone Number: +86-20-83827812; Email: yuxueqing@gdph.org.cn
• Study Contact Backup: Name: Zhiming ye; Phone Number: 138 2616 1678; Email: yezhiming@gdph.org.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Not yet recruiting
      • Beijing Hospital
      • Contact: Xin Liu
  • Fujian
    • Longyan, Fujian, China
      • Not yet recruiting
      • Longyan First Hospital
      • Contact: Senchao Wu
    • Zhangzhou, Fujian, China
      • Not yet recruiting
      • Zhangzhou Municipal Hospital of Fujian Province
      • Contact: Shanying Chen
  • Guangdong
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • The First Affiliated Hospital of Guangzhou Medical University
      • Contact: Jie Xiao
    • Guangzhou, Guangdong, China, 510080
      • Not yet recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Xueqing Yu; Phone Number: +86-20-83827812; Email: yuxueqing@gdph.org.cn
      • Contact: Zhiming Ye; Email: yezhiming@gdph.org.cn
    • Meizhou, Guangdong, China
      • Not yet recruiting
      • Meizhou People's Hospital
      • Contact: Shaoqing Xue
    • Shantou, Guangdong, China
      • Not yet recruiting
      • The First Affiliated Hospital of Shantou University Medical College
      • Contact: Yanqiang Peng
    • Shaoguan, Guangdong, China
      • Not yet recruiting
      • Yuebei People's Hospital
      • Contact: Min He
    • Zhongshan, Guangdong, China
      • Not yet recruiting
      • Zhongshan Hospital of Traditional Chinese Medicine
      • Contact: Yanlin Li
  • Guizhou
    • Zunyi, Guizhou, China
      • Not yet recruiting
      • Affiliated Hospital of Zunyi Medical University
      • Contact: Xiaoyong Yan
  • Hubei
    • Jingmen, Hubei, China
      • Not yet recruiting
      • Jingmen Central Hospital
      • Contact: Zhengli Quan
    • Shiyan, Hubei, China
      • Not yet recruiting
      • CNPG Dongfeng General Hospital
      • Contact: Huaqian Chen
    • Wuhan, Hubei, China
      • Recruiting
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
      • Contact: Gang Xu
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Wuhan Fourth Hospital
      • Contact: Hua Li
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Changsha Central Hospital
      • Contact: Rui Wen
  • Jiangsu
    • Nantong, Jiangsu, China
      • Not yet recruiting
      • NanTong First People's Hospital
      • Contact: Lianglan Shen
  • Liaoning
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • The First Hospital of China Medical University
      • Contact: Li Yao
  • Neimenggu
    • Baotou, Neimenggu, China
      • Not yet recruiting
      • The First Affiliated Hospital of Baotou Medical College
      • Contact: Caili Wang
  • Shandong
    • Jinan, Shandong, China
      • Not yet recruiting
      • The First Affiliated Hospital of Shandong First Medical University
      • Contact: Xueqing Tang
  • Sichuan
    • Yibin, Sichuan, China
      • Not yet recruiting
      • Yibin First People's Hospital
      • Contact: Wanchao Zhang
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Not yet recruiting
      • Tianjin First Center Hospital
      • Contact: Wenxiu Chang
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Hangzhou Xiaoshan First People's Hospital
      • Contact: Xiaoyun Zhang
    • Ningbo, Zhejiang, China
      • Not yet recruiting
      • The Affiliated People's Hospital of Ningbo University
      • Contact: Canxin Zhou
    • Wenzhou, Zhejiang, China
      • Not yet recruiting
      • Rui'an People's Hospital
      • Contact: Zengqi Xue

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age between 18-75 years, regardless of gender;
2. Body weight ≥ 45 kg, and body mass index (BMI) ≥ 18.5 kg/m²;
3. Diagnosis of chronic renal failure, and having undergone a stable regimen of peritoneal dialysis or hemodialysis for at least 12 weeks prior to enrollment (with stable hemofiltration at a frequency of every 2 or 4 weeks if applicable). Stable dialysis frequency and no plans to change the dialysis modality during the trial;
4. An up to standard dialysis adequacy testing result before randomization: spKt/V ≥ 1.2 for hemodialysis, Kt/V ≥ 1.7 for peritoneal dialysis;
5. Roxadustat dose ≤ 360 mg/week within 4 weeks before randomization, with stable dose; [Stable dose is defined as: (the maximum weekly dose within 4 weeks before randomization - the average weekly dose within 4 weeks before randomization) ÷ the maximum weekly dose within 4 weeks before randomization ≤ 30%];
6. Two pre-dialysis HB test values within 4 weeks before randomization of 8.0 - 12.0 g/dl, with an absolute difference between the two Hb values ≤ 1.3 g/dl, and an interval of ≥ 7 days between the two HB tests;
7. Serum ferritin level ≥ 100 μg/L and transferrin saturation (TAST) ≥ 20% at the time of testing before randomization, serum folate ≥ the lower limit of normal, and vitamin B12 ≥ the lower limit of normal;
8. Understanding of the study procedures and voluntary signing of the written informed consent form.

Exclusion Criteria:

1. Known autoimmune diseases, hematologic disorders (including congenital and acquired conditions such as thalassemia, Fanconi anemia, pure red cell aplasia, myelodysplastic syndrome, hemolytic anemia, and coagulation disorders), or other causes of anemia apart from CKD (such as gastrointestinal bleeding or hookworm disease).
2. Confirmed diagnosis of acquired immunodeficiency syndrome (AIDS), syphilis, or tuberculosis and currently undergoing treatment.
3. Known allergy to iron agents or polyethylene glycol molecules.
4. Treatment history with ESAs in combination with HIF-PHIs drugs within 8 weeks prior to randomization.
5. Underwent red blood cell or whole blood transfusion within 12 weeks prior to randomization.
6. Poorly controlled blood pressure (uncontrolled hypertension is defined as: during the screening period, systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg in two or more blood pressure measurements, or although the blood pressure values are below the aforementioned criteria, the investigator deems it necessary to adjust antihypertensive medications).
7. Active hepatitis or any of the following abnormal test results during the screening period (ALT ≥ 2 times the upper limit of normal, AST ≥ 2 times the upper limit of normal, DBIL ≥ 2 times the upper limit of normal, serum albumin < 2.5 g/dl).
8. Participants judged by the investigator to have uncontrolled or symptomatic secondary hyperparathyroidism, or those with blood iPTH > 800 pg/mL during the screening period.
9. C-reactive protein ≥ 30 mg/L during the screening period.
10. Cardiac function assessed as NYHA Class III or IV during the screening period.
11. Pregnant or breastfeeding women, or those planning to become pregnant during the study period.
12. Participants who plan to undergo kidney transplantation during the trial period or have already been kidney donors, or those who plan to undergo elective surgery during the trial period.
13. Participants deemed by the investigator to have any other factors that make them unsuitable for participation in this trial.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A1: Pegmolesatide 2mg SC; All patients in low-dose Roxadustat cohort randomised into this group will receive pegmolesatide 2mg subcutaneously once every 4 weeks.	Drug: Pegmolesatide 2mg SC; All patients will receive pegmolesatide 2mg subcutaneously once every 4 weeks.
Experimental: Arm A2: Pegmolesatide 4mg SC; All patients in low-dose Roxadustat cohort randomised into this group will receive pegmolesatide 4mg subcutaneously once every 4 weeks.	Drug: Pegmolesatide 4mg SC; All patients will receive pegmolesatide 4mg subcutaneously once every 4 weeks.
Experimental: Arm B1: Pegmolesatide 4mg SC; All patients in high-dose Roxadustat cohort randomised into this group will receive pegmolesatide 4mg subcutaneously once every 4 weeks.	Drug: Pegmolesatide 4mg SC; All patients will receive pegmolesatide 4mg subcutaneously once every 4 weeks.
Experimental: Arm B2: Pegmolesatide 6mg SC; All patients in high-dose Roxadustat cohort randomised into this group will receive pegmolesatide 6mg subcutaneously once every 4 weeks.	Drug: Pegmolesatide 6mg SC; All patients will receive pegmolesatide 6mg subcutaneously once every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of mean HB level	Change of mean HB level from baseline to 12 weeks and 16 weeks	from baseline to 12 weeks and 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of mean HB level	Change in mean HB levels from baseline to 12 weeks and 16 weeks, stratified by different baseline HB levels	from baseline to 12 weeks and 16 weeks
Changes in red blood cell count	Changes in red blood cell count from baseline to each follow-up	from baseline to 4 weeks, 8 weeks, 12 weeks, 16 weeks
Median time to the first HB value reaching 10.0-12.0 g/dl	Median time to the first HB value reaching 10.0-12.0 g/dl	From baseline to 4 weeks, 8 weeks,12 weeks and 16 weeks
Proportion of patients with HB 10.0-12.0 g/dl	Proportion of patients with HB 10.0-12.0 g/dl at each follow-up	from baseline to 4 weeks, 8 weeks,12 weeks and 16 weeks
Proportion of patients with HB 11.0-13.0 g/dl	Proportion of patients with HB11.0-13.0 g/dl at each follow-up	from baseline to 4 weeks, 8 weeks, 12 weeks and 16 weeks
Average drug dose at each follow-up		From baseline to 4 weeks, 8 weeks,12 weeks and 16 weeks
Adverse Events	Safety of therapy by Investigator.	From the start of study drug to 30 days after the last dose of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Maximum Plasma Concentration	The Maximum Plasma Concentration of Pegmolesatide	from the start of study drug to to 48 hours, 72 hours and 96 hours

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Investigators: Study Chair: Xueqing Yu, Guangdong Provincial People's Hospital; Study Director: Zhiming Ye, Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 31, 2025
• First Submitted That Met QC Criteria: August 20, 2025
• First Posted (Actual): August 22, 2025

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Renal Anemia
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Signs and Symptoms, Respiratory; Hypoxia; Kidney Diseases; Renal Insufficiency, Chronic; Anemia
• Other Study ID Numbers: KY2025-667-03

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