A Study of AND017 to Treat Anemia in Chronic Kidney Disease Patients on Dialysis
Study Details
Study Description
Brief Summary
This is a phase II study to evaluate the safety and efficacy of AND017 in renal anemia patients on dialysis
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a Phase II study to assess the safety and efficacy of AND017 in patients with CKD who are anemic and on dialysis.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AND017 Dose Regimen A AND017 will be administrated orally at dose A three times a week |
Drug: AND017
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
|
| Experimental: AND017 Dose Regimen B AND017 will be administrated orally at dose B once a week |
Drug: AND017
Orally, once per week in Period 1 and dose adjustment in Period 2 at 4 mg and 2-weeks interval according to Hb levels
|
| Active Comparator: Epoetin alfa Investigator will select appropriate epoetin alfa product for the patient under this arm with starting doses and dose adjustment rules according to the epoetin alfa USPI or SmPC. |
Drug: Epoetin Alfa
Dose regimen and adjustment rules according to the USPI or SmPC or local practice
|
Outcome Measures
Primary Outcome Measures
- Incidence of adverse events [Up to 20 weeks]
Incidence of adverse events
- Mean change from baseline in Hb at Week 6 [Up to 5 weeks after dosing]
Mean change from baseline in Hb at Week 6
Secondary Outcome Measures
- Proportion of responders, during the entire study period. [up to Week 20]
Responders are defined as patients whose Hb achieved ≥ 10.0 g/dL and an increase ≥ 1.0 g/dL from baseline
- Mean proportion of visits at which patients maintain Hb within the target range from baseline during the fixed-dose period and titration period [up to Week 20]
Target range is defined as 10.0-11.0 g/dL inclusive and an increase ≥ 1.0 g/dL.
- 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]
Proportion of patients with a mean Hb between 10.0-11.0 g/dL inclusive during 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]
Change in Hb from baseline to the mean Hb levels over Week 14-20
- Mean Hb levels and mean change from baseline in Hb level at each visit [up to Week 20]
Mean Hb levels and mean change from baseline in Hb level at each visit
- Cumulative response rate over the entire study period [up to Week 20]
Response is defined as Hb < 10.0 g/dL or an increase in hemoglobin of <1 g/dL from baseline
Other Outcome Measures
- EPO levels and change from baseline at each visit [up to Week 20]
EPO levels and change from baseline at each visit
- Hepcidin levels and change from baseline at each visit [up to Week 20]
Hepcidin levels and change from baseline at each visit
- Iron study levels and change from baseline at each visit [up to Week 20]
Iron study levels and change from baseline at each visit
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Body weight from 45 to 140 kg inclusive
-
Receiving HD or PD for end-stage renal disease for a minimum of 2 weeks and a maximum of 4 months, prior to screening
-
ESA naïve: for newly started dialysis (started <12 weeks before screening) patients should have never received ESA after starting dialysis; for maintenance dialysis (started ≥12 weeks before screening), patients should have not used ESA within 8 weeks before screening (including interruption of ESA therapy).
-
The mean of two hemoglobin values at a screening test and a follow-up hemoglobin test (at least one week apart from the screening test) must be < 10.0 g/dL with a difference of ≤1.3 g/dL between the two values
Key Exclusion Criteria:
-
Concurrent retinal neovascular lesions requiring treatment including proliferative diabetic retinopathy, exudative age-related macular degeneration, retinal vein occlusion, macular edema, etc.
-
Concurrent autoimmune disease with inflammatory symptoms (such as systemic erythematosus, ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, Sjögren's syndrome, celiac disease, etc.) that is possibly the principal cause of anemia.
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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 gastroparesis.
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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.
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Uncontrolled hypertension (more than one-third of identifiable diastolic blood pressure values >90 mmHg within 16 weeks prior to and including the screening assessment).
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Concurrent congestive heart failure (New York Heart Association [NYHA] Class III or higher).
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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.
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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.
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Not complying with COVID-19 prevention and control requirements per local policy.
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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.
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Known hemosiderosis, hemochromatosis or hyper-coagulable condition
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Known to be hypersensitive or intolerant to ESA.
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Having received treatment with androgenic anabolic steroids, testosterone enanthate, or mepitiostane within 8 weeks prior to the first dose.
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Any treatment with immune represents or systemic steroids within 12 weeks prior to the first dose.
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Any treatment with a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) within 8 weeks prior to the first dose.
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Total bilirubin >1.5 ULN, or aspartate aminotransferase (AST)>3 ULN, or alanine aminotransferase (ALT)>3 ULN, or alkaline phosphatase (ALP)>3 ULN, or previous or concurrent serious liver disease (acute or active chronic hepatitis, cirrhosis, etc.) thought to be caused by ESA.
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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).
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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.
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Patients that have major surgery planned during the study period.
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Patients that have undergone blood transfusion and/or a surgical procedure that caused major blood loss within 8 weeks before the screening assessment, or have major surgery planned during the study period. Investigators should discuss this with the Medical Monitor for cases where there is doubt about whether to exclude or not.
-
Patients need IV iron or don't agree to discontinue IV iron during the screening period.
-
Patients with a history or plan to have kidney transplant or without kidney.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Kind Pharmaceuticals LLC
Investigators
- Study Director: Yusha Zhu, MD, PhD, Kind Pharmaceuticals LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AND017-MN-202