Safety & Pharmacokinetics of Pegolsihematide for Treatment of Anemia Patient With Myelodysplastic Syndromes

Study Overview
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Brief Summary
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The primary objectives of the trial are to assess the safety and pharmacokinetics profile of pegolsihematide for treatment of anemia patient with myelodysplastic syndromes.

Detailed Description
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The study started from the lowest dose, 0.08mg/kg, each group will enroll 4 to 6 subjects.

Official Title
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Safety & Pharmacokinetics of Pegolsihematide for Treatment of Anemia Patient With Myelodysplastic Syndromes

Conditions
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Anemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Pegol-sihematide injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥18 years, premenopausal women must have negative pregnancy test. Documented diagnosis of myelodysplastic syndromes (MDS) according to World Health Organization (WHO) criteria, including refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD), MDS-U, 5q-. Meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease as determined by microscopic and standard cytogenetic analysis of the bone marrow during screening. Never with erythropoietin agents treatment prior to enrollment. Eastern cooperative oncology group (ECOG) performance status of 0 or 1 during screening. Hemoglobin ≥7g/dL and ≤10g/dL, at least two detections during screening. Adequate transferrin saturation (≥15%), ferritin (≥12ng/mL), folate (≥ lower limits of normal), vitamin B12 (≥ lower limits of normal) Patients understand and are able to provide written informed consent. Exclusion Criteria: Pregnant or breast feeding women or women having positive pregnant test, women or men whose spouse plan to become pregnant with 4 weeks after the end of treatment . Therapy-related or secondary MDS. Previously diagnosed with intermediate-2 or high risk MDS per International Prognostic Scoring System (IPSS). History of severe allergic or anaphylactic reactions or hypersensitivity to erythropoiesis-stimulating agents or polyethylene glycol. History of red blood cell or blood transfusion during 4 weeks prior to enrollment. Known other disease which can lead to anemia (including haemolytic disease and digestive tract hemorrhage). Uncontrolled hypertension 2 weeks prior to enrollment, defined as systolic blood pressure ≥160mmHg or diastolic blood pressure ≥ 95mmHg. Clinically significant systemic infection or uncontrolled chronic inflammatory disease (ie, rheumatoid arthritis, inflammatory bowel disease) as determined by the investigator at screening. Evidence of bone marrow collagen fibrosis, biopsy argentaffin staining showed reticular fiber ≥＋＋. History of deep venous thrombosis or arterial embolism within 12 months prior to enrollment. History of cardiocerebrovascular events within 6 months prior to enrollment, include local ischemia, embolism, cerebral hemorrhage, transient ischemic attack, myocardial ischemia or other arterial thrombosis. Any serious medical condition, lab abnormality or psychiatric illness within 6 months prior to enrollment. History of malignancies other than curatively treated non-melanoma skin or in situ carcinoma. Estimated survival time < 6 months. Plan to get major surgery which will lead to massive bleeding during the study. Treatment with any other investigational drug within 6 weeks prior to enrollment, or plan to participate in any other investigational drug during the study. Any other condition not specifically noted above which, in the judgement of the investigator, would preclude the patient from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.08mg/kg<br>Pegol-sihematide injection, 0.08mg/kg, single-dose | Drug: Pegol-sihematide injection<br>* single dose<br>* Other names: EPO-018B;|
| Experimental: 0.2mg/kg<br>Pegol-sihematide injection, 0.2mg/kg, single-dose | Drug: Pegol-sihematide injection<br>* single dose<br>* Other names: EPO-018B;|
| Experimental: 0.33mg/kg<br>Pegol-sihematide injection, 0.33mg/kg, single-dose | Drug: Pegol-sihematide injection<br>* single dose<br>* Other names: EPO-018B;|
| Experimental: 0.5mg/kg<br>Pegol-sihematide injection, 0.5mg/kg, single-dose | Drug: Pegol-sihematide injection<br>* single dose<br>* Other names: EPO-018B;|
| Experimental: 0.7mg/kg<br>Pegol-sihematide injection, 0.7mg/kg, single-dose | Drug: Pegol-sihematide injection<br>* single dose<br>* Other names: EPO-018B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | 28 days after injection | 
| Maximum Plasma Concentration [Cmax] |  | 10min before injection to 336h after injection | 
| Time to Maximum Plasma Concentration [Tmax] |  | 10min before injection to 336h after injection | 
| Half-life [t1/2] |  | 10min before injection to 336h after injection | 
| Area Under the Curve [AUC]). |  | 10min before injection to 336h after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of hemoglobin (g/L) after treatment |  | From date of recruitment until the date of biggest documented progression up to 28 weeks | 
| The changes of reticulocyte (10^9/L) after treatment |  | From date of recruitment until the date of biggest documented progression up to 28 weeks |