A Study of AND017 to Treat Anemia in Chronic Kidney Disease Patients on Dialysis

Study Overview
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Brief Summary
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This is a phase II study to evaluate the safety and efficacy of AND017 in renal anemia patients on dialysis

Detailed Description
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This is a Phase II study to assess the safety and efficacy of AND017 in patients with CKD who are anemic and on dialysis.

Official Title
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A Phase 2, Multicenter, Open-label, Randomized, Active-Controlled Study of Efficacy and Safety of AND017 in the Treatment of Anemia in Patients With Chronic Kidney Disease on Dialysis

Conditions
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Renal Anemia

Intervention / Treatment
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* Drug: AND017
* Drug: AND017
* Drug: epoetin alfa, darbepoetin alfa, Mircera®, or their biosimilars


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body weight from 45 to 140 kg inclusive Receiving stable HD (including combination methods such as hemodiafiltration or hemofiltration), HHD, or PD for ESKD for a minimum of 16 weeks prior to randomization and determined by the Investigator to be compliant with dialysis treatment prescription. Patient must have been on IV or SC of an approved ESA under the prescription for at least 6 weeks, and ≤25% change in dose between the two most recent doses, prior to randomization. The mean of two hemoglobin values during screening (at least 7 days apart) must be 9.0-11.0 g/dL with a difference of ≤1.3 g/dL between the two values TSAT ≥ 20% or ferritin ≥ 100 ng/mL at screening Folate ≥ 3.0 ng/mL and vitamin B12 ≥ lower limit of normal (LLN) at screening AST and ALT < 3×ULN at screening. No evidence of other causes of anemia caused by a pathologic process in the hematopoietic system, including intra- or extravascular hemolysis, or myelodysplasia. Key Exclusion Criteria: Concurrent retinal neovascular lesions requiring treatment including proliferative diabetic retinopathy, exudative age-related macular degeneration, retinal vein occlusion, macular edema, etc. Anemia determined by the Investigator to be caused by concurrent autoimmune disease with inflammatory symptoms (such as systemic erythematosus, ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, Sjögren's syndrome, celiac disease, etc.). History of gastric/intestinal resection considered influential on the absorption of drugs in the gastrointestinal tract (excluding resection of gastric or colon polyps) or concurrent symptomatic gastroparesis despite on treatment. Clinically significant bleeding (eg, requiring transfusion or drop in Hb of ≥ 2 g/dL) within 4 weeks of first dose; bleeding diathesis or risk of bleeding that has not been medically or surgically corrected at least 4 weeks prior to first dose of study drug. Uncontrolled hypertension defined as patients with hypertension having more than one of three diastolic blood pressure values >95 mmHg and each test at least 5 min apart during the screening assessment. Concurrent congestive heart failure (New York Heart Association [NYHA] Class III or higher). History of stroke, transient ischemic attack (TIA), myocardial infarction, thromboembolic event (deep vein thrombosis, DVT), pulmonary embolism, or lung infarction within 24 weeks before the screening assessment. Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody at the screening assessment, or positive for human immunodeficiency virus in a past test. Not complying with COVID-19 prevention and control requirements per local policy. Concurrent primary form of anemia other than renal anemia (hemolytic anemia, thalassemia, sickle cell anemia, history of pure red cell aplasia, history of myelodysplastic syndrome or multiple myeloma, iron deficiency, etc.). Any question of the primary cause of anemia should be discussed with the Medical Monitor before the patient signs informed consent. Known hemosiderosis, hemochromatosis or hyper-coagulable condition Known to be hypersensitive or intolerant to ESA. Having received treatment with androgenic anabolic steroids, testosterone enanthate, or mepitiostane within 5 weeks prior to the first dose. Any treatment with a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) within 5 weeks prior to the first dose. TBIL>1.5 ULN, or AST>3 ULN, or ALT>3 ULN, or ALP>3 ULN, or previous or concurrent serious liver disease (acute or active chronic hepatitis, cirrhosis, etc.) thought to be caused by any other HIF-PHI. Previous or current malignant tumor (patients with no recurrence for at least 5 years are eligible. Exemption: basal cell and squamous cell carcinoma not under active stage). Patients with a history of significant liver disease or active liver disease. Patients that have major surgery planned during the study period. Patients that have undergone blood transfusion or with evidence of major blood loss within 8 weeks before the screening assessment. Investigators should discuss this with the Medical Monitor for cases where there is doubt about whether to exclude or not. Patients unable to discontinue IV iron during the screening period. Patients with an organ transplant on immunosuppression, or with a scheduled kidney or any other organ transplant within the duration of the study, or without kidney. Serum albumin < 2.5 g/dL at screening. Patients with other chronic medical condition that may limit life expectancy in the opinion of the Investigator. History of a seizure disorder or any occurrence of seizures in the past.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AND017 Dose Regimen A<br>AND017 will be administrated orally at dose A three times a week | Drug: AND017<br>* Orally, 3 times per week in Period 1 and dose adjustment in Period 2 at 4 mg and 2-weeks interval according to Hb levels<br>|
| Experimental: AND017 Dose Regimen B<br>AND017 will be administrated orally at dose B once a week | Drug: AND017<br>* Orally, once per week in Period 1 and dose adjustment in Period 2 at 4 mg and 2-weeks interval according to Hb levels<br>|
| Active Comparator: Erythropoietin stimulating agent<br>Investigator will select an erythropoietin stimulating agent, such as epoetin alfa, darbepoetin alfa, Mircera®, or their biosimilars, for the patient under this arm with starting doses and dose adjustment rules according to the epoetin alfa USPI or SmPC. | Drug: epoetin alfa, darbepoetin alfa, Mircera®, or their biosimilars<br>* Dose regimen and adjustment rules according to the USPI or SmPC or local practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Incidence of adverse events | Up to 20 weeks | 
| Mean change from baseline in Hb at Week 6 | Mean change from baseline in Hb at Week 6 | Up to 5 weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of responders, during the entire study period. | Responders are defined as patients whose Hb achieved ≥ 10.0 g/dL and an increase ≥ 1.0 g/dL from baseline | up to Week 20 | 
| Mean proportion of visits at which patients maintain Hb within the target range from baseline during the fixed-dose period and titration period | Target range is defined as 10.0-11.0 g/dL inclusive and an increase ≥ 1.0 g/dL. | up to Week 20 | 
| Proportion of patients with a mean Hb between 10.0-11.0 g/dL inclusive during Week 14-20 | Proportion of patients with a mean Hb between 10.0-11.0 g/dL inclusive during Week 14-20 | at Week 14, 15, 16, 17, 18, 19, and 20 | 
| Change in Hb from baseline to the mean Hb levels over Week 14-20 | Change in Hb from baseline to the mean Hb levels over Week 14-20 | Baseline and at Week 14, 15, 16, 17, 18, 19, and 20 | 
| Mean Hb levels and mean change from baseline in Hb level at each visit | Mean Hb levels and mean change from baseline in Hb level at each visit | up to Week 20 | 
| Cumulative response rate over the entire study period | Response is defined as Hb < 10.0 g/dL or an increase in hemoglobin of <1 g/dL from baseline | up to Week 20 |