Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis (ALPS)

Astellas

Status and phase: Completed; Phase 3

Conditions: Anemia in Chronic Kidney Disease in Non-dialysis Patients

Treatments: Drug: Placebo; Drug: Roxadustat

Study type: Interventional

Funder types: Industry

Identifiers

NCT01887600

2012-005180-27 (EudraCT Number)

1517-CL-0608

Details and patient eligibility

About

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.

Full description

The study consisted of three study periods as follows:

• Screening period: up to 6 weeks
• Treatment period: minimum 52 weeks (primary treatment period) up to a maximum of 104 weeks (extended treatment period)
• Post-Treatment Follow-Up period: 4 weeks

Enrollment: 594 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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594 participants in 2 patient groups, including a placebo group

Roxadustat

Experimental group

Description:

Participants received roxadustat according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels 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. Participants received roxadustat for at least 52 weeks up to a maximum of 104 weeks.

Treatment:

Drug: Roxadustat

Placebo

Placebo Comparator group

Description:

Participants received matching placebo according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels 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. Participants received matching placebo for at least 52 weeks up to a maximum of 104 weeks.

Treatment:

Drug: Placebo