Clinical trial NCT04925661: HEC53856 Phase Ib Study in Patients With Non-dialysis Renal Anemia
Official title: Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HEC53856 Capsules in Patients With Non-dialysis Renal Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Kidney Diseases
Renal Anemia
Lead sponsor: Sunshine Lake Pharma Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Nicoya Therapeutics (Shanghai) Co., Ltd.
First posted: 2021-06-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients who agree to participate in this clinical trial and sign an informed consent form;
2. Age 18\~65 years old; Weight 40\~90Kg, including critical value;
3. 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;
4. 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:

1. 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;
2. 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.);
3. Those who have received blood transfusion within 3 months before the first administration;
4. Folic acid \<6.8nmol/L (3ng/ml) and (or) VitB12\<74pmol/L (100ng/ml) during the screening period;
5. 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;
6. Serum albumin \<3 g/dL;
7. 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;
8. Suffering from uncontrollable or symptomatic secondary hyperparathyroidism, plasma iPTH \> 500pg/ml;
9. A history of acute or chronic pancreatitis, or acute or chronic pancreatitis at the time of screening, or blood amylase \> or = 3×ULN;
10. 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;
11. 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;
12. 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.;
13. AIDS antibody, Treponema pallidum antibody, hepatitis B surface antigen or hepatitis C antibody positive for any of them;
14. People with a history of severe allergic disease or drug allergy, or those who are allergic to experimental drugs or their excipients;
15. Patients with clinically severe infections who are receiving systemic antibiotic treatment;
16. Those who have started dialysis or plan to start dialysis treatment within 6 months;
17. Anyone who has participated in or plans to participate in organ transplantation within 6 months;
18. Patients with hemoglobinosis, polycystic kidney disease, or no kidney;
19. 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;
20. Participated in other clinical trials within 3 months before screening (Definition of participation: accepted trial drug or instrument);
21. The investigator believes that there are other factors that are not suitable for participating in this trial.

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: Through study completion, an average of 12 weeks.
Secondary outcomes:
measure: AUC0-t
timeFrame: Day 1(Dosing) until Day 55 after single and multiple drug dosing.
measure: Cmax
timeFrame: Day 1(Dosing) until Day 55 after single and multiple drug dosing.
measure: Tmax
timeFrame: Day 1(Dosing) until Day 55 after single and multiple drug dosing.
measure: T½
timeFrame: Day 1(Dosing) until Day 55 after single and multiple drug dosing.
measure: Vz/F
timeFrame: Day 1(Dosing) until Day 55 after single and multiple drug dosing.
measure: Changes in mean hemoglobin
timeFrame: week 10
measure: Hemoglobin response
timeFrame: week 10
measure: E-AUC0-t
timeFrame: Day 1(Dosing) until Day 55 after single and multiple drug dosing.
measure: Emax
timeFrame: Day 1(Dosing) until Day 55 after single and multiple drug dosing.
measure: E-Tmax
timeFrame: Day 1(Dosing) until Day 55 after single and multiple drug dosing.
measure: Serum lipid
timeFrame: Up to Day 55
measure: Indicators of iron
timeFrame: Up to Day 55
measure: High-sensitivity C-reactive protein
timeFrame: Up to Day 55
measure: Reticulocytes
timeFrame: Up to Day 85
measure: VEGF
timeFrame: Up to Day 55
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The sixth Affiliated Hospital, Sun Yat-sen University
city: Hangzhou
country: China
facility: Zhejiang Provincal People's Hospital
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonmous Region
city: Shanghai
country: China
facility: Huashan Hospital
city: Shanghai
country: China
facility: Ruijin Hospital
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
Study officials:
References: