[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658598":3},{"organization":4,"outcomesModule":7,"designInfo":26,"detailedDescription":32,"studyPopulation":25,"armGroups":33,"interventions":41,"overallOfficials":25,"centralContacts":55,"locations":61,"responsibleParty":75,"collaborators":25,"id":79,"slug":80,"hasResults":81,"nctId":82,"briefTitle":83,"officialTitle":84,"acronym":25,"eligibilityCriteria":85,"healthyVolunteers":81,"sex":86,"minAge":87,"maxAge":25,"enrollmentInfo":88,"targetDuration":25,"studyType":91,"phases":92,"briefSummary":94,"conditions":95,"keywords":97,"overallStatus":64,"whyStopped":25,"lastUpdateSubmitDate":102,"lastUpdatePostDateStruct":103,"startDateStruct":106,"completionDateStruct":108,"leadSponsor":110,"locationsCount":111},{"fullName":5,"class":6},"Chinese University of Hong Kong","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":25,"otherOutcomes":25},[9,13,17,21],{"measure":10,"description":11,"timeFrame":12},"Incidence of platelet counts exceeding the normal range","The incidence of platelet counts exceeding the normal range, defined as an increase of more than 25% from baseline or platelet counts greater than 400 × 10\\^9\u002FL, following romiplostim administration in combination with ESAs.","From baseline through Week 24 and safety follow-up (Week 28)",{"measure":14,"description":15,"timeFrame":16},"Proportion of patients maintaining platelet counts within the normal range","Platelet counts within the normal range are defined as: (1) platelet counts do not increase by more than 25% from baseline; or (2) platelet counts do not exceed 400 × 10\\^9\u002FL. This outcome assesses the proportion of participants who maintain platelet counts within these limits during and after romiplostim treatment.","From baseline through Week 24 (end of treatment) and safety follow-up (Week 28)",{"measure":18,"description":19,"timeFrame":20},"Number and severity of adverse events (AEs) following romiplostim administration","All adverse events will be recorded from the time of informed consent until the last study-related procedure. Severity will be graded as mild, moderate, or severe. The relationship of each AE to study intervention will also be assessed. Serious adverse events (SAEs) will be reported within 24 hours of investigator awareness.","From informed consent through Week 28 (end of follow-up)",{"measure":22,"description":23,"timeFrame":24},"95% confidence interval of the increase in platelet counts after treatment","The 95% confidence interval of the change in platelet counts from baseline after treatment with romiplostim in combination with ESAs.","From baseline to Week 24",null,{"allocation":27,"interventionModel":28,"interventionModelDescription":25,"primaryPurpose":29,"observationalModel":25,"timePerspective":25,"maskingInfo":30},"NA","SINGLE_GROUP","TREATMENT",{"masking":31,"maskingDescription":25,"whoMasked":25},"NONE","Background and Rationale\n\nAnemia is a common complication of chronic kidney disease (CKD) and is associated with increased mortality and reduced quality of life. Erythropoiesis-stimulating agents (ESAs) have greatly reduced transfusion needs, but up to 20% of patients with CKD anemia are ESA-resistant or ESA-hyporesponsive. ESA resistance is clinically important because it is associated with higher risks of death and cardiovascular events. Treatment options for ESA-resistant anemia remain limited, and many patients eventually require recurrent transfusions.\n\nPreclinical studies by our group and others suggest that intensive ESA treatment can deplete early erythroid progenitor cells, contributing to ESA resistance. Thrombopoietin receptor agonists (TPO-RAs), such as romiplostim, can stimulate the expansion of hematopoietic stem cells and early erythroid progenitors, potentially correcting ESA-induced progenitor depletion. Because megakaryocytic and erythroid lineages share a common megakaryocyte-erythroid progenitor (MEP), concomitant ESA therapy may preferentially recruit MEPs into the erythroid lineage and indirectly inhibit platelet production through stem cell competition. This provides a mechanistic rationale for combining a TPO-RA with an ESA to treat ESA-resistant anemia while limiting the risk of thrombocytosis.\n\nThis Phase 2 study is designed to evaluate the safety and tolerability of adding romiplostim to ongoing ESA therapy in patients with CKD and ESA-resistant anemia. The current protocol focuses on the safety and dose-escalation portion of the study; a planned efficacy evaluation was removed in the current version.\n\nStudy Design\n\nThis is a single-center, open-label, Phase 2 dose-escalation trial conducted at the Division of Nephrology, Prince of Wales Hospital, The Chinese University of Hong Kong. The study uses sequential cohorts of four participants each, with a total of 12 participants planned. Romiplostim is administered by subcutaneous injection once weekly for three consecutive weeks at one of three dose levels: 0.2 mg\u002Fkg, 0.5 mg\u002Fkg, or 1 mg\u002Fkg. The 1 mg\u002Fkg once-weekly dose is the approved starting dose for immune thrombocytopenic purpura (ITP); lower doses are included because patients with anemia may have higher baseline platelet counts and potentially stronger platelet responses than patients with ITP.\n\nThe study is open-label, and all participants receive active romiplostim as an add-on to their existing ESA therapy. There is no placebo or control group. No formal interim analysis is planned. Safety oversight is provided by an independent Data and Safety Monitoring Board (DSMB), which reviews serious adverse events, thrombotic events, and bleeding events.\n\nParticipants and Intervention\n\nParticipants are adults with CKD receiving chronic hemodialysis who have anemia resistant to ESAs. Only hemodialysis patients are enrolled because the protocol requires relatively frequent blood sampling to monitor platelet responses, which is more feasible in this population than in pre-dialysis patients. All participants continue their pre-study ESA, either darbepoetin alfa or Mircera, together with iron supplementation. ESA doses are initially unchanged. If hemoglobin rises too rapidly, for example by more than 1 g\u002FdL over 2 weeks, ESA dose reduction may be performed according to product labels.\n\nRomiplostim is given as three weekly subcutaneous injections. After the 3-week romiplostim dosing period, participants continue their ESA therapy and are monitored through Week 24, with a safety follow-up visit approximately 4 weeks after the End-of-Treatment visit.\n\nAssessments and Safety Monitoring\n\nSafety is the primary focus of this study. Participants undergo frequent monitoring of platelet counts, hemoglobin, and other hematologic parameters. In the initial weeks, blood sampling is performed weekly; later monitoring occurs every 4 weeks. Safety assessments include adverse event (AE) and serious adverse event (SAE) reporting, clinical laboratory tests, electrocardiograms, vital signs, and physical examinations. Laboratory tests include complete blood counts, liver function tests, renal function tests, and electrolytes.\n\nAEs are assessed for severity and relationship to study intervention. SAEs must be reported to the sponsor within 24 hours of investigator awareness. Events of special interest include overdose, suspected abuse or misuse, medication errors, and inadvertent or accidental exposure. Pregnancy is monitored; women of childbearing potential must have negative pregnancy tests and use acceptable contraception during the study. The DSMB reviews safety data at regular intervals, including at least semiannually, and provides recommendations regarding study continuation or modification.\n\nPharmacokinetic\u002FPharmacodynamic and Biomarker Strategy\n\nBlood samples for pharmacokinetic (PK) and pharmacodynamic (PD) analyses are collected together with hematology samples when possible. Biomarkers include erythroferrone (ERFE), hepcidin, ferritin, transferrin, transferrin saturation, total iron, reticulocyte count, mean corpuscular volume, mean corpuscular hemoglobin, hematocrit, and red blood cell count.\n\nThe PK and PD data will be combined to develop a mechanism-based PK-PD model. Model-based simulations will then be performed to explore optimal dosing regimens and titration strategies for romiplostim combined with ESAs. This in silico approach has previously been used to inform romiplostim dosing in patients with ITP.\n\nStatistical Considerations\n\nThe sample size of 12 participants is considered adequate to characterize the safety of romiplostim in this setting, given that the clinical safety of romiplostim has been previously demonstrated. No formal efficacy hypothesis testing is planned. Descriptive statistics will be used to summarize demographic, baseline, safety, and laboratory variables. Continuous variables will be summarized using mean, median, standard deviation, minimum, and maximum; categorical variables will be summarized using counts and percentages. Time-to-event measures, such as time to platelet counts above the normal range, will be analyzed using Kaplan-Meier methods. AEs will be summarized by treatment dose, severity, and relationship to study intervention. PK and PD data will be summarized by dose and time point, and PK\u002FPD modeling will be conducted. Exploratory analyses will evaluate changes in erythroid response and iron-status biomarkers.\n\nRegulatory and Ethical Oversight\n\nThe trial will be conducted in accordance with the Declaration of Helsinki, International Council for Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements. The protocol, informed consent forms, and other participant materials will be approved by the Institutional Review Board before study initiation. Participation is voluntary, and participants may withdraw at any time without affecting their medical care. Data will be recorded in case report forms and source documents, monitored for quality and compliance, and kept confidential according to institutional and regulatory requirements. The study may be suspended or terminated if unexpected or unacceptable risks are identified, if required by regulators, or if the study cannot be conducted according to protocol requirements.",[34],{"label":35,"type":36,"description":25,"interventionNames":37},"Romiplostim plus ESA (dose escalation)","EXPERIMENTAL",[38,39,40],"Drug: Romiplostim","Drug: darbepoetin alfa","Drug: Methoxy Polyethylene Glycol-Epoetin Beta",[42,47,51],{"type":43,"name":44,"description":45,"armGroupLabels":46,"otherNames":25},"DRUG","Romiplostim","Romiplostim is a thrombopoietin receptor agonist (TPO-RA) administered as an add-on therapy to erythropoiesis-stimulating agents (ESAs) in patients with ESA-resistant anemia. In this study, romiplostim is given by subcutaneous injection once weekly for 3 consecutive weeks at a dose of 0.2, 0.5, or 1 mg\u002Fkg. It is intended to stimulate hematopoietic stem cells and megakaryocyte-erythroid progenitors to correct ESA-induced progenitor depletion while limiting platelet increase through stem cell competition with concomitant ESA therapy.",[35],{"type":43,"name":48,"description":49,"armGroupLabels":50,"otherNames":25},"darbepoetin alfa","Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) used as standard therapy for anemia in chronic kidney disease. Participants continue their pre-study darbepoetin alfa dose together with iron supplementation. The ESA dose is initially unchanged; it may be reduced according to product labeling if hemoglobin rises too rapidly (e.g., \\>1 g\u002FdL over 2 weeks). It is given as part of the combination therapy with romiplostim.",[35],{"type":43,"name":52,"description":53,"armGroupLabels":54,"otherNames":25},"Methoxy Polyethylene Glycol-Epoetin Beta","Methoxy polyethylene glycol-epoetin beta is a long-acting erythropoiesis-stimulating agent (ESA) used for anemia in chronic kidney disease. Participants continue their pre-study Mircera dose together with iron supplementation. The ESA dose is initially unchanged; it may be reduced according to product labeling if hemoglobin rises too rapidly (e.g., \\>1 g\u002FdL over 2 weeks). It is given as part of the combination therapy with romiplostim.",[35],[56],{"name":57,"role":58,"phone":59,"phoneExt":25,"email":60},"Xiaoyu Yan, PhD","CONTACT","85239435012","xiaoyuyan@cuhk.edu.hk",[62],{"facility":63,"status":64,"city":65,"state":25,"zip":25,"country":65,"countryCode":66,"cosmosGeoPoint":67,"geoPoint":72,"contacts":73},"The Chinese University of Hong Kong","RECRUITING","Hong Kong","HK",{"type":68,"coordinates":69},"Point",[70,71],114.17469,22.27832,{"lat":71,"lon":70},[74],{"name":57,"role":58,"phone":59,"phoneExt":25,"email":60},{"type":76,"investigatorFullName":77,"investigatorTitle":78,"investigatorAffiliation":5,"oldNameTitle":25,"oldOrganization":25},"PRINCIPAL_INVESTIGATOR","Xiaoyu Yan","Associate Professor","100658598","phase-2-combination-therapy-of-romiplostim-and-erythropoiesis-stimulating-agents-100658598",false,"NCT07854561","Combination Therapy of Romiplostim and Erythropoiesis-stimulating Agents","A Clinical Trial to Evaluate the Safety of the Combination Therapy of Romiplostim and Erythropoiesis-stimulating Agents (ESAs) in ESA-resistant Anemic Patients","Inclusion Criteria:\n\n1. Previously failed treatment with erythropoiesis-stimulating agents (ESAs) or had a poor response to ESAs. ESA resistance is defined as:\n\n   * Transfusion-dependent patients requiring a minimum dose of \\>=40,000 units of epoetin alfa\u002Fweek for 8 weeks, or an equivalent dose of darbepoetin alfa (1.5 mg\u002Fkg\u002Fweek or 120 mg every 2 weeks) or Mircera (100 mg every 2 weeks) for 8 weeks, with failure to achieve transfusion independence; OR\n   * Non-transfusion-dependent patients who fail to achieve a \\>=2 g increase in hemoglobin (Hgb) level sustained for \\>=4 weeks.\n2. Male or female subjects at least 18 years of age.\n3. Currently receiving darbepoetin or Mircera for anemia and iron supplement.\n4. Receiving chronic maintenance hemodialysis for end-stage kidney disease. Note: Only hemodialysis patients will be enrolled because frequent blood sampling is required.\n5. Having symptomatic anemia without transfusion and with Hgb levels \\\u003C9.5 g\u002FdL for \\\u003C=8 weeks, or being RBC transfusion-dependent (i.e., \\>=2 units\u002Fmonth) for \\\u003C=8 weeks.\n6. For non-transfusion-dependent patients (i.e., receiving \\\u003C2 units\u002F4 weeks for 8 weeks pre-study) who receive periodic transfusions, the mean 8-week pre-transfusion Hgb level will be used to determine protocol eligibility and response reference.\n7. For non-transfusion-dependent patients, a minimum of two pre-transfusion or untransfused Hgb values are required.\n8. Ability to sign informed consent.\n9. Accessible vein for blood sampling.\n10. Not pregnant or breastfeeding (in the case of women).\n\nExclusion Criteria:\n\n1. Anemia due to a cause other than chronic kidney disease (CKD), such as iron deficiency (defined as transferrin saturation \\[TSAT\\] \\\u003C20%) or the presence of active bleeding or recent blood loss.\n2. Hematological disease: sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia (thalassemia trait), or pure red cell aplasia.\n3. Cardiovascular diseases, such as stroke or myocardial infarction, in the past 6 months, or poorly controlled hypertension, i.e., systolic blood pressure \\>160 mmHg or diastolic blood pressure \\>100 mmHg.\n4. A history of cancer.\n5. Active infection or other chronic inflammatory conditions.\n6. Baseline platelet count \\>300 x 10\\^9\u002FL.\n7. Vascular access problems or susceptibility to vascular access thrombosis.","ALL","18 Years",{"count":89,"type":90},12,"ESTIMATED","INTERVENTIONAL",[93],"PHASE2","The goal of this Phase 2 clinical trial is to learn if adding romiplostim to standard erythropoiesis-stimulating agent (ESA) therapy is safe and tolerated in adults with chronic kidney disease who are on hemodialysis and have anemia that has not responded well to ESAs. The study will mainly check platelet counts and side effects. The main questions it aims to answer are:\n\nHow many participants keep platelet counts within a normal range during and after treatment?\n\nHow many participants have platelet counts that rise above the normal range?\n\nWhat medical problems or side effects occur after romiplostim is added to ESA therapy?\n\nResearchers will study three dose levels of romiplostim (0.2, 0.5, and 1 mg\u002Fkg) in small groups of participants. There is no placebo group. All participants will receive romiplostim plus their usual ESA and iron supplement. The study will also measure changes in hemoglobin and iron-related blood markers.\n\nParticipants will:\n\nReceive romiplostim as an injection under the skin once weekly for 3 weeks. Each participant will be assigned to one of three dose groups.\n\nContinue their usual ESA therapy (darbepoetin or Mircera) and iron supplement.\n\nHave blood tests to check platelet counts, hemoglobin, and other blood and iron measures. Blood tests will be frequent at first and then less often.\n\nVisit the clinic regularly for up to 24 weeks, with a follow-up visit about 4 weeks after the end-of-treatment visit.\n\nHave other safety checks, such as vital signs, physical exams, and electrocardiograms (ECGs).",[96],"Anemia Associated With Chronic Kidney Disease",[98,99,100,101],"ESA resistance","erythropoiesis","erythropoietin","romiplostim","2026-09-28",{"date":104,"type":105},"2026-10-02","ACTUAL",{"date":107,"type":105},"2026-08-11",{"date":109,"type":90},"2027-09-01",{"name":5,"class":6},1]