HEC53856 Phase Ib Study in Patients With Non-dialysis Renal Anemia

Study Overview
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Brief Summary
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To evaluate the safety, tolerability , pharmacokinetics and Preliminary Efficacy of HEC53856 Capsules in Patients With Non-dialysis Renal Anemia.

Detailed Description
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This is a MultiCenter, Randomized, Blinded, Active Drug and Placebo-controlled, Dose-escalated Phase Ib Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HEC53856 Capsules in Patients With Non-dialysis Renal Anemia. Each part participants will be randomly administrated for HEC53856 or placebo or roxadustat. The study consisted of three study periods as follows: Screening period: up to 2 weeks； Treatment period: 8 weeks； Post-Treatment Follow-Up period: 4 weeks.

Official Title
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Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HEC53856 Capsules in Patients With Non-dialysis Renal Anemia

Conditions
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Chronic Kidney Diseases, Renal Anemia

Intervention / Treatment
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* Drug: HEC53856
* Drug: Roxadustat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who agree to participate in this clinical trial and sign an informed consent form; Age 18 65 years old; Weight 40 90Kg, including critical value; Glomerular filtration rate (eGFR) calculated by CKD-EPI formula 15mL/min/1.73 m^2 < or = eGFR < 60 mL/min/1.73 m^2 diagnosed chronic kidney disease patients who have not received dialysis; The hemoglobin values obtained during the last two screening periods at least 6 days apart must be > or = 8.0 g/dL and <10 g/dL. Exclusion Criteria: Existence of diseases or conditions other than nephropathy that may cause anemia, including but not limited to 1) blood system diseases, such as thalassemia, aplastic anemia, hemolytic anemia, multiple myeloma, myelodysplastic syndrome, etc.; 2) may affect red blood cells The resulting autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, etc.; 3) Bleeding diseases, such as gastrointestinal bleeding, obstetrics and gynecology bleeding diseases, etc.; 4) Elective surgery expected during the study period; Drugs used to treat anemia within 8 weeks before the first administration, including but not limited to erythropoiesis stimulators (ESAs) and their derivatives, hypoxia inducible factor prolyl hydroxylase inhibitors (HIF-PHI), androgens And anabolic hormone drugs, intravenous iron, Chinese patent medicine, Chinese herbal medicine, etc. (Can accept patients who have used a fixed dose of oral iron within 4 weeks before screening, and continue to take it during the screening period and the first 4 weeks after starting to take the test drug The fixed dose remains unchanged.); Those who have received blood transfusion within 3 months before the first administration; Folic acid <6.8nmol/L (3ng/ml) and (or) VitB12<74pmol/L (100ng/ml) during the screening period; Clinically significant chronic liver and gallbladder disease, or obvious abnormal liver function: ALT>3×ULN and/or AST>3×ULN, or total bilirubin>1.5×ULN; Serum albumin <3 g/dL; The mean systolic blood pressure > or = 160 mmHg and/or the diastolic blood pressure > or = 100 mmHg of the two blood pressure measurements at least one hour apart during the screening period; Suffering from uncontrollable or symptomatic secondary hyperparathyroidism, plasma iPTH > 500pg/ml; A history of acute or chronic pancreatitis, or acute or chronic pancreatitis at the time of screening, or blood amylase > or = 3×ULN; History of malignant tumors within 5 years (except for cured skin basal cell carcinoma and cervical carcinoma in situ), or current assessment of potential malignant tumors; Patients with acute coronary syndrome, stroke ( except for lacunar infarction )or thromboembolic diseases (such as deep vein thrombosis or pulmonary embolism) occurred in the 6 months before screening; New York Society of Cardiology, grade III or IV congestive heart failure, or severe arrhythmia, including but not limited to atrial fibrillation, III degree atrioventricular block, etc.; AIDS antibody, Treponema pallidum antibody, hepatitis B surface antigen or hepatitis C antibody positive for any of them; People with a history of severe allergic disease or drug allergy, or those who are allergic to experimental drugs or their excipients; Patients with clinically severe infections who are receiving systemic antibiotic treatment; Those who have started dialysis or plan to start dialysis treatment within 6 months; Anyone who has participated in or plans to participate in organ transplantation within 6 months; Patients with hemoglobinosis, polycystic kidney disease, or no kidney; Women during pregnancy or lactation, or fertile men and women who refuse to take effective contraceptive measures voluntarily from the beginning of screening to 4 weeks after the administration of the last trial drug; Participated in other clinical trials within 3 months before screening (Definition of participation: accepted trial drug or instrument); The investigator believes that there are other factors that are not suitable for participating in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEC53856<br>Drug: HEC53856 TIW dosing, capsule There will be a total of 3 dose cohorts: 100mg, 150mg, 200 mg | Drug: HEC53856<br>* Either dose of HEC53856 will be administered after fasting .<br>|
| Active Comparator: Roxadustat<br>Drug: roxadustat TIW dosing There will be only one cohort: 70mg | Drug: Roxadustat<br>* Roxadustat will be administered after fasting .<br>|
| Placebo Comparator: Placebo<br>Drug: placebo TIW dosing, capsule There will be a total of 3 dose cohorts: 100mg, 150mg, 200 mg | Drug: Placebo<br>* Either dose of placebo will be administered after fasting .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | To assess the safety and tolerability of therapy by incidence of treatment-emergent adverse events after multiple doses of HEC53856 capsule | Through study completion, an average of 12 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t | Area under the concentration versus time curve (AUC) from time zero to the time of the last quantifiable concentration | Day 1(Dosing) until Day 55 after single and multiple drug dosing. | 
| Cmax | Maximum observed plasma concentration | Day 1(Dosing) until Day 55 after single and multiple drug dosing. | 
| Tmax | Time of the maximum observed plasma concentration | Day 1(Dosing) until Day 55 after single and multiple drug dosing. | 
| T½ | Apparent terminal elimination half-life | Day 1(Dosing) until Day 55 after single and multiple drug dosing. | 
| Vz/F | Apparent volume of distribution | Day 1(Dosing) until Day 55 after single and multiple drug dosing. | 
| Changes in mean hemoglobin | Changes in mean hemoglobin (Hb) relative to baseline during weeks 8 and 10. | week 10 | 
| Hemoglobin response | Percentage of subjects who met the hemoglobin response after dosing | week 10 | 
| E-AUC0-t | Area under the EPO concentration versus time curve (AUC) from time zero to the time of the last quantifiable concentration | Day 1(Dosing) until Day 55 after single and multiple drug dosing. | 
| Emax | Maximum observed EPO concentration | Day 1(Dosing) until Day 55 after single and multiple drug dosing. | 
| E-Tmax | Time of the maximum observed EPO concentration | Day 1(Dosing) until Day 55 after single and multiple drug dosing. | 
| Serum lipid | Changes in Serum lipid relative to baseline at weeks 8. | Up to Day 55 | 
| Indicators of iron | Changes in the Indicators of iron relative to baseline at weeks 8. | Up to Day 55 | 
| High-sensitivity C-reactive protein | Changes in the High-sensitivity C-reactive protein relative to baseline at weeks 8. | Up to Day 55 | 
| Reticulocytes | Changes in the mean Reticulocytes relative to baseline after doses. | Up to Day 85 | 
| VEGF | Changes in the VEGF relative to baseline after doses. | Up to Day 55 |