Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis
Condition: Anemia
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia
Intervention: Roxadustat; Placebo
Intervention description: 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.; 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2781.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Renal,; CKD,; Roxadustat,; anemia,; non-dialysis

Summary:

      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
    

Eligibility criteria:

        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