Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis
Condition: Anemia in Chronic Kidney Disease in Non-dialysis Patients
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia
Intervention: Roxadustat; Placebo
Intervention description: Roxadustat was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with > 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL.; Placebo was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with > 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 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: 594.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: anemia; chronic kidney disease (CKD); Hemoglobin (Hb); non-dialysis

Summary:

      This study was conducted to treat anemia in patients with chronic kidney disease. Anemia is a
      reduced number of red blood cells or hemoglobin. Hemoglobin is important for the transport of
      oxygen in your blood. The purpose of the study was to see if Roxadustat is both effective and
      safe as a treatment for anemia in patients with chronic kidney disease.
    

Eligibility criteria:

        Inclusion criteria:

          -  Participant has a diagnosis of chronic kidney disease, with Kidney Disease Outcomes
             Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving dialysis; with an Estimated
             Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m^2 estimated using the abbreviated
             4-variable Modification of Diet in Renal Disease (MDRD) equation.

          -  The mean of the Participant's three most recent Hb values during the Screening period,
             obtained at least 4 days apart, must be less than or equal to 10.0 g/dL, with a
             difference of less than or equal to 1.0 g/dL between the highest and the lowest
             values. The last Hb value must be within 10 days prior to randomization.

          -  Participant has a ferritin level greater than or equal to 30 ng/mL (greater than or
             equal to 67.4 pmol/L) at screening.

          -  Participant has a transferrin saturation (TSAT) level greater than or equal to 5% at
             screening.

          -  Participant has a serum folate level greater than or equal to lower limit of normal at
             screening.

          -  Participant has a serum vitamin B12 level greater than or equal to lower limit of
             normal at screening.

          -  Participant's alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels
             are less than or equal to 3 x upper limit of normal (ULN), and total bilirubin (TBL)
             is less than or equal to 1.5 x ULN.

          -  Participant's body weight is 45.0 kg up to a maximum of 160.0 kg.

        Exclusion criteria:

          -  Participant has received any ESA treatment within 12 weeks prior to randomization.

          -  Participant has had more than one dose of IV iron within 12 weeks prior to
             randomization.

          -  Participant has received a RBC transfusion within 8 weeks prior to randomization.

          -  Participant has a known history of myelodysplastic syndrome or multiple myeloma.

          -  Participant has a known hereditary hematologic disease such as thalassemia or sickle
             cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD.

          -  Participant has a known hemosiderosis, hemochromatosis, coagulation disorder, or
             hypercoagulable condition.

          -  Participant has chronic inflammatory disease that could impact erythropoiesis (e.g.,
             systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is
             currently in remission.

          -  Participant is anticipated to have elective surgery that is expected to lead to
             significant blood loss or anticipated elective coronary revascularization.

          -  Participant has active or chronic gastrointestinal bleeding.

          -  Participant has received any prior treatment with roxadustat or a hypoxia-inducible
             factor Prolyl Hydroxylase Inhibitor (HIF-PHI).

          -  Participant has been treated with iron-chelating agents within 4 weeks prior to
             randomization.

          -  Participant has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the
             liver)

          -  Participant has a known New York Heart Association Class III or Intravenous (IV)
             congestive heart failure.

          -  Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure,
             or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior
             to randomization.

          -  Uncontrolled hypertension or two or more blood pressure (BP) values of systolic BP
             (SBP) greater than or equal to 160 mmHg or diastolic BP (DBP) greater than or equal to
             95 mmHg confirmed by repeat measurement within 2 weeks prior to randomization.

          -  Participant has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak
             Category 2F or higher) of renal cell carcinoma on renal ultrasound within 12 weeks
             prior to randomization.

          -  Participant has a history of malignancy, except the following: cancers determined to
             be cured or in remission for greater than or equal to 5 years, curatively resected
             basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic
             polyps.

          -  Participant is positive for any of the following: Human Immunodeficiency Virus (HIV);
             hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab).

          -  Participant has an active clinically significant infection manifested by White Blood
             Count (WBC) > ULN, and/or fever, in conjunction with clinical signs or symptoms of
             infection within one week prior to randomization.

          -  Participant has a known untreated proliferative diabetic retinopathy, diabetic macular
             edema, macular degeneration and retinal vein occlusion.

          -  Participant has had any prior organ transplant (that has not been explanted) or a
             scheduled organ transplantation.

          -  Participant has participated in any interventional clinical study or has been treated
             with any investigational drugs within 30 days or 5 half lives or limit set by national
             law, whichever is longer, prior to the initiation of Screening.

          -  Participant has an anticipated use of dapsone in any dose amount or chronic use of
             acetaminophen (paracetamol) > 2.0 g/day during the treatment or follow-up period of
             the study.

          -  Participant has a history of alcohol or drug abuse within 2 years prior to
             randomization.