Combination Therapy of Romiplostim and Erythropoiesis-stimulating Agents
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorChinese University of Hong Kong
About this trial
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:
How many participants keep platelet counts within a normal range during and after treatment?
How many participants have platelet counts that rise above the normal range?
What medical problems or side effects occur after romiplostim is added to ESA therapy?
Researchers will study three dose levels of romiplostim (0.2, 0.5, and 1 mg/kg) 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.
Participants will:
Receive romiplostim as an injection under the skin once weekly for 3 weeks. Each participant will be assigned to one of three dose groups.
Continue their usual ESA therapy (darbepoetin or Mircera) and iron supplement.
Have blood tests to check platelet counts, hemoglobin, and other blood and iron measures. Blood tests will be frequent at first and then less often.
Visit the clinic regularly for up to 24 weeks, with a follow-up visit about 4 weeks after the end-of-treatment visit.
Have other safety checks, such as vital signs, physical exams, and electrocardiograms (ECGs).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Transfusion-dependent patients requiring a minimum dose of >=40,000 units of epoetin alfa/week for 8 weeks, or an equivalent dose of darbepoetin alfa (1.5 mg/kg/week or 120 mg every 2 weeks) or Mircera (100 mg every 2 weeks) for 8 weeks, with failure to achieve transfusion independence; OR
Non-transfusion-dependent patients who fail to achieve a >=2 g increase in hemoglobin (Hgb) level sustained for >=4 weeks.
Male or female subjects at least 18 years of age.
Currently receiving darbepoetin or Mircera for anemia and iron supplement.
Disqualifiers
Anemia due to a cause other than chronic kidney disease (CKD), such as iron deficiency (defined as transferrin saturation [TSAT] <20%) or the presence of active bleeding or recent blood loss.
Hematological disease: sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia (thalassemia trait), or pure red cell aplasia.
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.
A history of cancer.
Trial design
Design model
Single group
Treatments tested in this trial
Romiplostim
DrugRomiplostim 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/kg. 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.
darbepoetin alfa
DrugDarbepoetin 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/dL over 2 weeks). It is given as part of the combination therapy with romiplostim.
Methoxy Polyethylene Glycol-Epoetin Beta
DrugMethoxy 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/dL over 2 weeks). It is given as part of the combination therapy with romiplostim.
Treatment groups
12 Participants
are divided into 1 treatment groupGroup A: Romiplostim plus ESA (dose escalation)Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
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/L, following romiplostim administration in combination with ESAs.
Time frame
From baseline through Week 24 and safety follow-up (Week 28)2
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/L. This outcome assesses the proportion of participants who maintain platelet counts within these limits during and after romiplostim treatment.
Time frame
From baseline through Week 24 (end of treatment) and safety follow-up (Week 28)3
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.
Time frame
From informed consent through Week 28 (end of follow-up)4
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.
Time frame
From baseline to Week 24Sponsors and contacts
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Source ClinicalTrials.gov