A Study of AND017 to Evaluate Efficacy and Safety in Patients With Anemia Due to Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD)

Official title

A Phase 3, Multi-center, Randomized, Open-Label, Active-Controlled, Efficacy and Safety Study of AND017 to Treat Anemia in Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD) Patients

Overview

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

• Drug AND017
  AND017 capsules administered orally with a starting dose of 8 mg TIW for ESA naive patients or 10 mg TIW for ESA treated patients
• Drug ESA
  ESA injection and dose based on package insert and local practice

Primary outcome measures

• Evaluate the efficacy of AND017 compared with the active control in maintaining Hemoglobin (Hb) levels in patients with anemia due to CKD [Time frame: From Week 23 to Week 27]

Secondary outcome measures (12)

• The percentage of responders [Time frame: From baseline to Week 27]
• Percentage of participants that maintained Hb level over target lower limit [Time frame: From Week 5 to Week 27]
• Maintenance of Hb within 10.0-12.0 g/dL after initial achievement ≥10.0 g/dL during the entire study treatment period [Time frame: From baseline to Week 53]
• Incidence of extreme Hb levels of ≥13.0 g/dL or <7.5 g/dL during the entire study treatment period [Time frame: From baseline to Week 53]
• Incidence of excessive erythropoiesis [Time frame: From baseline to Week 53]
• The cumulative incidence of Hb non-response [Time frame: From baseline to Week 27]
• Mean Hb change from baseline averaged over Weeks 5-27 [Time frame: From baseline to Week 27]
• Mean Hb change from baseline averaged over Weeks 23-27 [Time frame: From baseline to Week 27]
• Mean Hb change from baseline averaged over Weeks 13-17 [Time frame: From baseline to Week 17]
• Mean Hb change from baseline averaged over Weeks 27-53 [Time frame: From baseline to Week 53]
• Mean Hb change from baseline averaged over Weeks 49-53 [Time frame: From baseline to Week 53]
• During the entire treatment period, mean Hb at each visit [Time frame: From baseline to Week 53]

Eligibility criteria

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

• 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;
• 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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University People's Hospital — Beijing

Identifiers

NCT: NCT07487727 · AND017-CN-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗