Renal Anemia
Conditions
Brief summary
This is a phase II study to evaluate the safety and efficacy of AND017 in renal anemia patients on dialysis
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.
Interventions
DRUGAND017 capsules TIW
Orally, 3 times per week in Period 1 and dose adjustment in Period 2 at 2 mg/4 mg and 2-weeks interval according to Hb levels
DRUGAND017 capsules QW
Orally, once per week in Period 1 and dose adjustment in Period 2 at 4 mg/8 mg and 2-weeks interval according to Hb levels
DRUGepoetin alfa, darbepoetin alfa, Mircera®, or their biosimilars
Dose regimen and adjustment rules according to the USPI or SmPC or local practice
Sponsors
Kind Pharmaceuticals LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Body weight from 45 to 140 kg inclusive 2. 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. 3. 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. 4. 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 5. TSAT ≥ 20% or ferritin ≥ 100 ng/mL at screening 6. Folate ≥ 3.0 ng/mL and vitamin B12 ≥ lower limit of normal (LLN) at screening 7. AST and ALT \< 3×ULN at screening. 8. 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
1. Concurrent retinal neovascular lesions requiring treatment including proliferative diabetic retinopathy, exudative age-related macular degeneration, retinal vein occlusion, macular edema, etc. 2. 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.). 3. 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. 4. 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. 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 (TIA), myocardial infarction, thromboembolic event (deep vein thrombosis, DVT), pulmonary embolism, or lung infarction within 24 weeks before the screening assessment. 8. 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. 9. Not complying with COVID-19 prevention and control requirements per local policy. 10. 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. 11. Known hemosiderosis, hemochromatosis or hyper-coagulable condition 12. Known to be hypersensitive or intolerant to ESA. 13. Having received treatment with androgenic anabolic steroids, testosterone enanthate, or mepitiostane within 5 weeks prior to the first dose. 14. Any treatment with a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) within 5 weeks prior to the first dose. 15. 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. 16. 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). 17. Patients with a history of significant liver disease or active liver disease. 18. Patients that have major surgery planned during the study period. 19. 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. 20. Patients unable to discontinue IV iron during the screening period. 21. 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. 22. Serum albumin \< 2.5 g/dL at screening. 23. Patients with other chronic medical condition that may limit life expectancy in the opinion of the Investigator. 24. History of a seizure disorder or any occurrence of seizures in the past.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in Hb at Week 6 | Up to 5 weeks after dosing | Mean change from baseline in Hb at Week 6 |
| Incidence of adverse events | Up to 20 weeks | Incidence of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China, United States
Outcome results
None listed