A Study of AND017 to Treat Anemia in Non-dialysis-Dependent Chronic Kidney Disease (NDD-CKD) Patients

Study Overview
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Brief Summary
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This is a pilot phase II study to evaluate the safety and efficacy of AND017 in NDD-CKD patients

Detailed Description
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This is a pilot phase 2, multicenter, randomized, parallel-group, double-blind, placebo-controlled, dose-ranging, safety and efficacy study of oral AND017 to treat anemia in non-dialysis-dependent chronic kidney disease patients.

Official Title
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A Pilot Phase II Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Dose-Ranging, Safety and Efficacy Study of Oral AND017 to Treat Anemia in Nondialysis-Dependent Chronic Kidney Disease (NDD-CKD) Patients

Conditions
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Renal Anemia

Intervention / Treatment
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* Drug: AND017
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of chronic kidney disease, not receiving dialysis, with an eGFR <60 mL/min/1.73 m2. Baseline Hb level ≥ 7.5 g/dL and <10.0 g/dL. TSAT ≥ 20% or ferritin ≥ 100 ng/mL at screening test Serum folate and vitamin B12 ≥ lower limit of normal at screening test AST and ALT ≤ 3×ULN. Total bilirubin ≤ 1.5×ULN. 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 that is possibly mainly caused by concurrent autoimmune disease with inflammatory symptoms History of gastric/intestinal resection considered to affect the absorption of drugs in the gastrointestinal tract (excluding resection of gastric or colon polyps) or concurrent symptomatic gastroparesis despite being on treatment. Clinically significant bleeding (eg, requiring transfusion or drop in Hb of ≥ 2g/dL) within 4 weeks of first dose; no 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, myocardial infarction, thromboembolic event, pulmonary embolism, or lung infarction within 24 weeks before the screening assessment. Concurrent anemia due to another cause other than renal anemia Known hemosiderosis, hemochromatosis or hyper-coagulable condition Any treatment with a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) within 5 weeks before randomization. Having received treatment with erythropoiesis stimulating agents, androgenic anabolic steroids, testosterone enanthate, or mepitiostane within 5 weeks before the first dose. Total bilirubin >1.5xULN, or AST>3xULN, or ALT>3xULN, or ALP>3xULN, or previous or concurrent serious liver disease (acute or active chronic hepatitis, cirrhosis, etc.) thought to be caused by ESAs. Patients with a history of significant liver disease or active liver disease. Investigators should discuss this with the Medical Monitor for cases where there is doubt about whether to exclude or not. 13. Patients that have major surgery planned during the study period. 14. Having undergone blood transfusion and/or a surgical procedure within 8 weeks before the screening assessment. 15. Having undergone a kidney transplantation. 16. History of a seizure disorder or any occurrence of seizures in the past

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 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 A<br>AND017 will be administrated orally at dose A | Drug: AND017<br>* Orally, 3 times per week in Period 1 and randomize to TIW or QW group at the same dose in Period 2<br>|
| Experimental: AND017 Dose B<br>AND017 will be administrated orally at dose B | Drug: AND017<br>* Orally, 3 times per week in Period 1 and randomize to TIW or QW group at the same dose in Period 2<br>|
| Experimental: AND017 Dose C<br>AND017 will be administrated orally at dose C | Drug: AND017<br>* Orally, 3 times per week in Period 1 and randomize to TIW or QW group at the same dose in Period 2<br>|
| Placebo Comparator: Placebo<br>Placebo will be administrated orally | Drug: Placebo<br>* Orally, 3 times per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Evaluations | Incidence of adverse events | Up to 17 weeks | 
| Rate of rise in hemoglobin for each of 3 dose levels as compared with placebo from baseline to 5 weeks after TIW oral dosing | Calculate the slope of a linear regression for each patient using all hemoglobin data collected during the Fixed-Dose Period | Up to 5 weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hb response to treatment during Period 1 | Cumulative percentage of patients with Hb ≥10.0 g/dL | Up to 5 weeks after dosing | 
| Percentage of responder patients | Responder is defined as a hemoglobin ≥10.0 g/dL and an increase in hemoglobin by ≥1.0 g/dL | Up to 13 weeks after dosing | 
| Percentage of visits at which patients maintain hemoglobin between 10.0-11.0 g/dL after achieving hemoglobin ≥10.0 g/dL | Percentage of visits at which patients maintain hemoglobin between 10.0-11.0 g/dL after achieving hemoglobin ≥10.0 g/dL | Up to 13 weeks after dosing | 
| Change from baseline in Hb | Change from baseline in Hb | Up to 13 weeks after dosing | 
| Change in hemoglobin levels from baseline to the mean of weeks 10-13 | Change in hemoglobin levels from baseline to the mean of weeks 10-13 | Baseline and at Week 10, 11, 12, 13, and 14 | 
| Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit | Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit | Up to 13 weeks after dosing | 
| Mean Hb levels at weeks 6-14 including the average of weeks 10-13 | Mean Hb levels at weeks 6-14 including the average of weeks 10-13 | Up to 13 weeks after dosing | 
| Cumulative incidence of lack of response over the entire treatment period | Hb level < 10.0 g/dL and an increase in hemoglobin from baseline of < 1 g/dL | Up to13 weeks after dosing | 
| To assess changes in the levels of PD indicator - EPO | To assess changes in the levels of EPO | Baseline and at Week 2, 4, 6, 8, 10, 12, 14, and 28 days after the last dose | 
| To assess changes in the levels of PD indicator - hepcidin | To assess changes in the levels of hepcidin | Baseline and at Week 2, 4, 6, 8, 10, 12, 14, and 28 days after the last dose | 
| To assess iron utilization parameter during treatment - transferrin level | To assess transferrin level during treatment | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | 
| To assess iron utilization parameter during treatment - total iron-binding capacity (TIBC) | To assess TIBC level during treatment | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | 
| To assess iron utilization parameter during treatment - transferrin saturation (TSAT) | To assess TSAT level during treatment | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | 
| To assess iron utilization parameters during treatment - ferritin | To assess ferritin level during treatment | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | 
| To assess iron utilization parameters during treatment - serum iron | To assess serum iron level during treatment | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose |