Anemia Due to Chronic Kidney Disease
Conditions
Keywords
anemia, CKD
Brief summary
This is a Phase III, randomized, open-label, active-controlled study to evaluate the safety and efficacy of AND017 in non-dialysis-dependent (NDD)-CKD patients compared with the active control, ESA treatment
Interventions
Sponsors
Kind Pharmaceuticals LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * A diagnosis of CKD confirmed at screening, KDOQI CKD stage 3, 4, or 5 defined by estimated Glomerular Filtration Rate (eGFR) using the CKD Epidemiology Collaboration (EPI) formula. * Not on dialysis and no clinical evidence of impending need to initiate dialysis during the study treatment. * Prior ESA and hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) treatment 1. ESA/HIF-PHI-naïve: Defined as no use of any ESA/HIF-PHI treatment for at least 12 weeks before randomization; Mean of the two most recent Hb values during the screening period obtained at least 7 days apart must be ≥7.5 g/dL and \<10.0 g/dL with a difference of ≤1.3 g/dL between the two values; 2. ESA-treated: Defined as having received an approved ESA, administered intravenously or subcutaneously, for at least 6 weeks prior to randomization, with no change in ESA product and no treatment interruption exceeding 2 consecutive weeks; Mean of the two most recent Hb values during the screening period obtained at least 7 days apart must be 9.0-12.0 g/dL inclusive. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3× upper limit of normal (ULN) * Transferrin saturation (TSAT) ≥20% or ferritin ≥100 ng/mL at screening test * Serum folate and vitamin B12 ≥ lower limit of normal (LLN) at screening test Key
Exclusion criteria
* Concurrent retinal neovascular lesions requiring treatment. * Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis or concurrent autoimmune disease with inflammatory symptoms. * History of gastric/intestinal resection considered to affect the absorption of drugs in the gastrointestinal tract or concurrent symptomatic gastroparesis despite being on treatment. * Uncontrolled hypertension, defined as patients with hypertension having more than one of three systolic blood pressure \>180 mmHg, or diastolic blood pressure \>110 mmHg 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. * Participants with a history of significant liver disease or active liver disease. * History of a seizure disorder or any occurrence of seizures in the past. * Serum albumin (ALB) \< 2.5 g/dL at screening test. * Prior ESA/HIF-PHI treatment caused total bilirubin \>1.5xULN, or AST/ALT/ALP\>3xULN, or serious liver disease (acute or active chronic hepatitis, cirrhosis, etc.). * Any prior functioning organ transplant or a scheduled organ transplantation, or anephric.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the efficacy of AND017 compared with the active control in maintaining Hemoglobin (Hb) levels in patients with anemia due to CKD | From Week 23 to Week 27 | The mean Hb levels averaged over Week 23-27 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The percentage of responders | From baseline to Week 27 | Responder is defined as: for participants with baseline Hb ≥ 9.0 g/dL, mean Hb ≥ 10.0 g/dL and a change from baseline ≥ -1.0 g/dL during Weeks 23-27; for participants with baseline Hb \< 9.0 g/dL, an increase in Hb from baseline ≥ 1.0 g/dL (for) during Weeks 3-27 |
| Percentage of participants that maintained Hb level over target lower limit | From Week 5 to Week 27 | Percentage of participants with mean Hb ≥ 10.0 g/dL averaged over Weeks 5-27 |
| Maintenance of Hb within 10.0-12.0 g/dL after initial achievement ≥10.0 g/dL during the entire study treatment period | From baseline to Week 53 | During entire study treatment period, the percentage of participants in which Hb, after first reaching ≥ 10.0 g/dL, is maintained within the target range of 10.0-12.0 g/dL (inclusive) |
| Incidence of extreme Hb levels of ≥13.0 g/dL or <7.5 g/dL during the entire study treatment period | From baseline to Week 53 | During the entire study treatment period, the percentage of participants in which Hb is ≥ 13.0 g/dL or \< 7.5 g/dL |
| Incidence of excessive erythropoiesis | From baseline to Week 53 | During the entire study treatment period, the percentage of participants with an Hb increase ≥ 1.0 g/dL within any 2-week period and an Hb increase ≥ 2.0 g/dL within any 4-week period respectively |
| The cumulative incidence of Hb non-response | From baseline to Week 27 | The cumulative incidence of Hb non-response is defined as Hb \< 10.0 g/dL and an increase from baseline \< 1.0 g/dL averaged over Weeks 5-27. |
| Mean Hb change from baseline averaged over Weeks 5-27 | From baseline to Week 27 | Mean Hb change from baseline averaged over Weeks 5-27 |
| Mean Hb change from baseline averaged over Weeks 23-27 | From baseline to Week 27 | Mean Hb change from baseline averaged over Weeks 23-27 |
| Mean Hb change from baseline averaged over Weeks 13-17 | From baseline to Week 17 | Mean Hb change from baseline averaged over Weeks 13-17 |
| Mean Hb change from baseline averaged over Weeks 27-53 | From baseline to Week 53 | Mean Hb change from baseline averaged over Weeks 27-53 |
| Mean Hb change from baseline averaged over Weeks 49-53 | From baseline to Week 53 | Mean Hb change from baseline averaged over Weeks 49-53 |
| During the entire treatment period, mean Hb at each visit | From baseline to Week 53 | During the entire treatment period, mean Hb at each visit |
| The use of intravenous iron during the entire study treatment period | From baseline to Week 53 | The percentage of participants that have received intravenous iron during the entire study treatment period |
| The mean weekly dose of intravenous iron during the entire treatment period | From baseline to Week 53 | The mean weekly dose of intravenous iron during the entire treatment period |
| The time to first initiation of intravenous iron during the entire treatment period | From baseline to Week 53 | The time to first initiation of intravenous iron during the entire treatment period |
Countries
China
Contacts
CONTACTYusha Zhu, MD, PhD
STUDY_DIRECTORYusha Zhu, MD, PhD
Kind Pharmaceuticals LLC
Outcome results
None listed