Renal Anemia
Conditions
Brief summary
This is a pilot phase II study to evaluate the safety and efficacy of AND017 in NDD-CKD patients
Detailed description
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.
Interventions
DRUGAND017
Orally, 3 times per week in Period 1 and randomize to TIW or QW group at the same dose in Period 2
DRUGPlacebo
Orally, 3 times per week
Sponsors
Kind Pharmaceuticals LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Diagnosis of chronic kidney disease, not receiving dialysis, with an eGFR \<60 mL/min/1.73 m2. 2. Baseline Hb level ≥ 7.5 g/dL and \<10.0 g/dL. 3. TSAT ≥ 20% or ferritin ≥ 100 ng/mL at screening test 4. Serum folate and vitamin B12 ≥ lower limit of normal at screening test 5. AST and ALT ≤ 3×ULN. 6. Total bilirubin ≤ 1.5×ULN. Key
Exclusion criteria
1. Concurrent retinal neovascular lesions requiring treatment including proliferative diabetic retinopathy, exudative age-related macular degeneration, retinal vein occlusion, macular edema, etc. 2. Anemia that is possibly mainly caused by concurrent autoimmune disease with inflammatory symptoms 3. 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. 4. 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. 5. 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. 6. Concurrent congestive heart failure (New York Heart Association \[NYHA\] Class III or higher). 7. History of stroke, transient ischemic attack, myocardial infarction, thromboembolic event, pulmonary embolism, or lung infarction within 24 weeks before the screening assessment. 8. Concurrent anemia due to another cause other than renal anemia 9. Known hemosiderosis, hemochromatosis or hyper-coagulable condition 10. Any treatment with a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) within 5 weeks before randomization. 11. Having received treatment with erythropoiesis stimulating agents, androgenic anabolic steroids, testosterone enanthate, or mepitiostane within 5 weeks before the first dose. 12. 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. 13. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Evaluations | Up to 17 weeks | Incidence of adverse events |
| Rate of rise in hemoglobin for each of 3 dose levels as compared with placebo from baseline to 5 weeks after TIW oral dosing | Up to 5 weeks after dosing | Calculate the slope of a linear regression for each patient using all hemoglobin data collected during the Fixed-Dose Period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Percentage of visits at which patients maintain hemoglobin between 10.0-11.0 g/dL after achieving hemoglobin ≥10.0 g/dL |
| Change from baseline in Hb | Up to 13 weeks after dosing | Change from baseline in Hb |
| Change in hemoglobin levels from baseline to the mean of weeks 10-13 | Baseline and at Week 10, 11, 12, 13, and 14 | Change in hemoglobin levels from baseline to the mean of weeks 10-13 |
| Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit | Up to 13 weeks after dosing | Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit |
| Mean Hb levels at weeks 6-14 including the average of weeks 10-13 | Up to 13 weeks after dosing | Mean Hb levels at weeks 6-14 including the average of weeks 10-13 |
| Cumulative incidence of lack of response over the entire treatment period | Up to13 weeks after dosing | Hb level \< 10.0 g/dL and an increase in hemoglobin from baseline of \< 1 g/dL |
| Hb response to treatment during Period 1 | Up to 5 weeks after dosing | Cumulative percentage of patients with Hb ≥10.0 g/dL |
| To assess changes in the levels of PD indicator - hepcidin | 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 hepcidin |
| To assess iron utilization parameter during treatment - transferrin level | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | To assess transferrin level during treatment |
| To assess iron utilization parameter during treatment - total iron-binding capacity (TIBC) | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | To assess TIBC level during treatment |
| To assess iron utilization parameter during treatment - transferrin saturation (TSAT) | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | To assess TSAT level during treatment |
| To assess iron utilization parameters during treatment - ferritin | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | To assess ferritin level during treatment |
| To assess iron utilization parameters during treatment - serum iron | Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose | To assess serum iron level during treatment |
| To assess changes in the levels of PD indicator - 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 EPO |
| Percentage of responder patients | Up to 13 weeks after dosing | Responder is defined as a hemoglobin ≥10.0 g/dL and an increase in hemoglobin by ≥1.0 g/dL |
Countries
China, United States
Outcome results
None listed