Dataset Information

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

ABSTRACT:

Background

Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies.

Methods

A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691.

Findings

Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported.

Interpretation

Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients.

Funding

The study was supported by Hansoh Medical Development Group.

SUBMITTER: Zhang P

PROVIDER: S-EPMC10632410 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Zhang Ping P Jiang Yan Y Xu Chunping C Zhou Linghui L Zheng Hongguang H Xie Deqiong D Guo Minghao M Huang Xiangyang X Lu Guoyuan G Jiang Hongli H Qiu Hongyu H Liu Bicheng B Li Shaomei S Chen Qinkai Q Xia Yu'ou Y Sun Bengui B Yang Xiao X Zhang Shiying S Du Shutong S Sun Mindan M Chen Menghua M Zhong Aimin A Wang Xiaoling X Zhao Zhanzheng Z Zhou Hua H Li Guisen G Ren Yueqin Y Luo Qun Q Yang Aicheng A Luo Ping P Tang Shuifu S Xu Chengyun C Wang Qin Q Wang Xiaoxia X Yan Tiekun T He Wei W Qin Shuguang S Zhang Weili W Lv Lu L Wang Cheng C Liu Hong H Li Jing J Wu Qiong Q Pan Chao C Li Chuan C He Liangliang L Chen Jianghua J

EClinicalMedicine 20231028

<h4>Background</h4>Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies.<h4>Methods</h4>A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in Ch ...[more]

PMID: 37954906

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Project description:ImportanceDaprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported.ObjectiveTo evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients.Design, setting, and participantsThis prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete.InterventionsRandomized 1:1 to daprodustat or darbepoetin alfa.Main outcomes and measuresThe primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability.ResultsA total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa.Conclusions and relevanceThis randomized clinical trial found that daprodustat was noninferior to darbepoetin alfa in treating anemia of CKD and may represent a potential oral alternative to a conventional ESA in the ID population.Trial registrationClinicalTrials.gov Identifier: NCT03029208.

Dataset Information

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Background

Methods

Findings

Interpretation

Funding

Publications

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

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