Chronic Kidney Disease 5D, Dialysis; Complications, Renal Anaemia, Renal Anemia, Chronic, Renal Anemia of Chronic Kidney Disease
Conditions
Keywords
recombinant human erythropoietin, erythropoietin mimetic peptides, Pegmolesatide, Dialysis, renal anemia
Brief 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.
Detailed 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.
Interventions
DRUGThe rHuEPO Monotherapy Group (Control Group)
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.
DRUGThe Pegmolesatide and Roxadustat Combination Therapy Group (Exploratory Group)
The Pegmolesatide and Roxadustat Combination Therapy Group (Exploratory Group) will receive a combination of Pegmolesatide and roxadustat throughout the entire 24-week treatment period.
DRUGThe Pegmolesatide Monotherapy Group (Experimental group)
The Pegmolesatide Monotherapy Group (Experimental Group) will receive Pegmolesatide treatment throughout the entire 24-week period.
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Chinese PLA General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in mean hemoglobin (Hb) levels from baseline at weeks 12 to 16 of treatment in the three groups. | During weeks 12 to 16 of the study treatment | Primary efficacy endpoints |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The absolute values of hemoglobin (Hb) levels during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
| The dosage of the study drug used between each pair of consecutive follow-up visits during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
| The average dosage of the study drug used by participants with Hb levels within the target range (100 g/L ≤ Hb ≤ 120 g/L) at each follow-up visit during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
| The average dosage of the study drug used by participants with Hb levels within the target range (110 g/L ≤ Hb ≤ 130 g/L) at each follow-up visit during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
| The total number of dosage adjustments at weeks 12 and 24 in the three groups. | At weeks 12 and 16 of the study treatment | secondary efficacy endpoints |
| The rate of Hb increase during the first 4 weeks and first 8 weeks of treatment in the three groups. | during the first 4 weeks and first 8 weeks of treatment in the three groups. | secondary efficacy endpoints |
| The proportion of participants receiving rescue therapy during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
| The proportion of participants in the three groups with mean Hb levels ≥100 g/L and ≤120 g/L at weeks 12 to 16 and weeks 20 to 24 of treatment. | During weeks 12 to 16 and weeks 20 to 24 of the study treatment | secondary efficacy endpoints |
| The proportion of participants in the three groups with mean Hb levels ≥110 g/L and ≤130 g/L at weeks 12 to 16 and weeks 20 to 24 of treatment. | During weeks 12 to 16 and weeks 20 to 24 of the study treatment | secondary efficacy endpoints |
| The proportion of participants in the three groups with mean Hb levels ≥100 g/L at weeks 12 to 16 and weeks 20 to 24 of treatment. | During weeks 12 to 16 and weeks 20 to 24 of the study treatment | secondary efficacy endpoints |
| The proportion of participants in the three groups with mean Hb levels ≥110 g/L at weeks 12 and 24 of treatment. | at weeks 12 and 24 of treatment. | secondary efficacy endpoints |
| The median time to first reach the target Hb level (110-130 g/L) during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
| The absolute values of changes in hemoglobin (Hb) levels from baseline during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
| The absolute values of red blood cell (RBC) count levels during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
| The absolute values of hematocrit levels during the treatment period in the three groups. | up to 24 weeks | secondary efficacy endpoints |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subgroup analysis based on different baseline characteristics | up to 24 weeks | Exploratory endpoints |
| Thromboembolic events: It is necessary to distinguish whether the thromboembolic events are related to blood vessels or catheters, and to identify whether they are caused by thrombus formation. | up to 24 weeks | Safety endpoints |
| Hyperkalemia: The incidence of hyperkalemia will be observed in the three groups. | up to 24 weeks | Safety endpoints |
| Major adverse cardiovascular events (MACE): The types, severity, and incidence of MACE will be reported. MACE includes death, non-fatal myocardial infarction, and stroke. | up to 24 weeks | Safety endpoints |
| The change in carbamylated EPO levels from baseline at week 16 of treatment in the three groups. | The change from baseline data at week 16 of treatment | Exploratory endpoints |
| Artificial intelligence (AI)-predicted rational dosing regimens for medications. | through study completion, an average of 1 year | Upon completion of the experiment and collection of relevant data from the participants, we will employ artificial intelligence and machine learning techniques to model and train our database. This process will involve the development of an artificial intelligence-based predictive model. This model will be capable of forecasting individual patients' needs for peginesatide to maintain hemoglobin (Hb) levels within the target range, as well as predicting monthly dose adjustments for peginesatide. Ultimately, this approach aims to optimize anemia management in patients with chronic kidney disease (CKD). |
Countries
China
Contacts
Primary ContactPing Li, M.D.
Outcome results
None listed