Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis

AstraZeneca2,781 enrolled

Overview

The purpose of the study is to evaluate the safety and efficacy of roxadustat for treatment of anemia in patients with chronic kidney disease not on dialysis

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in anemic patients with Stage 3, 4 or 5 chronic kidney disease (CKD) who are not on dialysis.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

2,781

Conditions

Anemia

Interventions

RoxadustatDRUG

The initial study drug dose is 70 mg three times a week (TIW). The dose is subsequently adjusted to achieve and maintain Hb 11±1 g/dL.

PlaceboDRUG

The initial study drug dose is 70 mg three times a week (TIW). The dose is subsequently adjusted to achieve and maintain Hb 11±1 g/dL.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedures. 2. Age ≥18 years at screening visit 1 3. eGFR \<60 mL/min/1.73 m2, (calculated by central lab) corresponding to stage 3, 4 or 5CKD according to the Kidney Disease Outcomes Quality Initiative (KDOQI), not receiving dialysis 4. Mean of 2 most recent central laboratory Hb values during the screening period, obtained at least 7 days apart, must be \<10.0 g/dL 5. Ferritin ≥50 ng/mL at randomization (obtained from screening visit) 6. TSAT ≥15 % at randomization (obtained from screening visit) 7. Serum folate level ≥ lower limit of normal (LLN) at randomization (obtained from screening visit) 8. Serum vitamin B12 level ≥LLN at randomization (obtained from screening visit) 9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin (Tbili) ≤1.5 x ULN at randomization (obtained from screening visit) 10. Body weight 45 to 160 kg Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous randomization in the present study 3. Any erythropoietin analogue treatment within 6 weeks of randomization 4. New York Heart Association Class III or IV congestive heart failure at enrollment 5. Myocardial infarction (MI), acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization 6. History of chronic liver disease (e.g., chronic infectious hepatitis, chronic auto- immune liver disease, cirrhosis or fibrosis of the liver) 7. Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than CKD 8. Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis) 9. Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. CT scan or MRI) conducted at screening or within 12 weeks prior to randomization 10. Systolic BP ≥160 mmHg or diastolic BP ≥95 mmHg (confirmed by repeated measurement), within 2 weeks prior to randomization. Patients may be rescreened once BP controlled 11. History of prostate cancer, breast cancer or any other malignancy, except the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps 12. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab) 13. Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia 14. Known hemosiderosis, hemochromatosis or hypercoagulable condition 15. Any prior organ transplant or a scheduled organ transplantation date 16. Any red blood cell transfusion (RBC) during the screening period 17. Any current condition leading to active significant blood loss 18. Any treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) 19. Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 1 month of the first administration of IP in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded) 20. History of alcohol or drug abuse within 2 years prior to randomization 21. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence 22. Pregnant or breastfeeding females 23. Known allergy to the investigational product or any of its ingredients 24. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound efficacy or safety assessment or may interfere with study participation

Locations (359)

Outcomes

Primary Outcomes

Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to mean value from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation analysis of covariance (ANCOVA) model with baseline Hb, baseline estimated glomerular filtration rate (eGFR), cardiovascular (CV) history, geographic region and treatment group as fixed effect covariates. The adjusted least squares (LS) mean estimates of change from baseline to mean during Week 28 to Week 52 are presented.

Time frame: Baseline (Day 1, Week 0) and Week 28 to Week 52.

Secondary Outcomes

Percentage of Participants With Hb Response During the First 24 Weeks of Treatment

Hb response was defined as: * Hb ≥ 11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL for participants with baseline Hb \> 8.0 g/dL; or * Hb increase from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at 2 consecutive visits (with available data) separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell \[RBC\] transfusion, erythropoietin analogue, or intravenous \[IV\] iron) prior to Hb response. The percentage of participants with an Hb response during the first 24 weeks of treatment is presented.

Time frame: Baseline (Day 1, Week 0) up to Week 24.

Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 in Participants With Baseline High Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)

Baseline hsCRP was quantified from stored biomarker samples obtained at randomization. Baseline Hb was defined as the mean of the last 3 central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to mean value during Week 28 to Week 52 was analyzed using a MAR based multiple imputation ANCOVA model with baseline Hb, baseline eGFR, CV history, geographic region and treatment group as fixed effect covariates. The adjusted LS mean estimates of change from baseline in participants with baseline hsCRP \>ULN to mean during Week 28 to Week 52 are presented.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.