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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
FibroGen
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01887600
First received: June 25, 2013
Last updated: June 6, 2017
Last verified: June 2017
  Purpose
This study is 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 is to see if Roxadustat is both effective and safe as a treatment for anemia in patients with chronic kidney disease.

Condition Intervention Phase
Anemia in Chronic Kidney Disease in Non-dialysis Patients Drug: Roxadustat Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):

Primary Outcome Measures:
  • Hemoglobin (Hb) response to treatment with Roxadustat without the use of rescue therapy [ Time Frame: Up to week 24 ]
  • Change in Hb from Baseline (BL) to the average level regardless of rescue therapy [ Time Frame: Baseline and week 28 to week 52 ]

Secondary Outcome Measures:
  • Hb maintenance: Hb change from BL to the average Hb, without having received rescue therapy within 6 weeks prior to and during the 8-week evaluation period (weeks 28 to 36) [ Time Frame: Baseline and weeks 28 to 36 ]
  • Change from BL in low-density lipoprotein (LDL) cholesterol to the average value of LDL cholesterol [ Time Frame: Baseline and weeks 12 to 28 ]
  • Use of rescue therapy [ Time Frame: Up to 24 weeks ]
    Rescue therapy: composite of Red Blood Cell (RBC) transfusions, Erythropoiesis-Stimulating Agent (ESA) use and Intravenous (IV) iron

  • Time to use of rescue therapy [ Time Frame: Up to 24 weeks ]
  • Change from BL in Short Form (SF)-36 Physical Functioning (PF) subscore to the average SF-36 PF subscore [ Time Frame: Baseline and weeks 12 to 28 ]
  • Change from BL in SF-36 Vitality (VT) subscore to the average SF-36 VT subscore [ Time Frame: Baseline and weeks 12 to 28 ]
  • Change from BL in Mean Arterial Pressure (MAP) to the average MAP [ Time Frame: Baseline and weeks 20 to 28 ]
  • Occurrence of hypertension [ Time Frame: Up to week 108 ]
    Defined as either systolic blood pressure [SBP] > 170 mmHg and an increase from BL greater than or equal to 20 mmHg or as DBP > 110 mmHg, and an increase from BL of greater than or equal to 15 mmHg)

  • Time to occurrence of hypertension [ Time Frame: Up to week 108 ]
  • Hb averaged over weeks 28-36, without use of rescue therapy within 6 weeks prior to and during the evaluation period [ Time Frame: Up to week 36 ]
  • Time to achieve the first Hb response as defined by primary endpoint [ Time Frame: Up to week 24 ]
  • Hb change from BL to each post-dosing time point [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Hb level averaged over weeks 44-52, without use of rescue therapy within 6 weeks prior to and during the evaluation period [ Time Frame: Up to week 52 ]
  • Hb change from BL to the average Hb value, regardless of the use of rescue therapy [ Time Frame: Baseline, week 28 to week 36 and week 44 to week 52 ]
  • Proportion of Hb values within 10.0-12.0 g/dL in weeks 28-36, without use of rescue therapy within 6 weeks prior to and during the 8-week evaluation period [ Time Frame: Up to week 36 ]
  • Occurrence of hospitalization [ Time Frame: Up to End of Treatment (EOT) (Up to week 104) ]
  • Number of days of hospitalization [ Time Frame: Up to End of Treatment (EOT) (Up to week 104) ]
  • Number of subjects having received RBC transfusions [ Time Frame: Up to End of Treatment (EOT) (Up to week 104) ]
  • Number of RBC packs per subject [ Time Frame: Up to End of Treatment (EOT) (Up to week 104) ]
  • Volume of RBC transfused per subject [ Time Frame: Up to End of Treatment (EOT) (Up to week 104) ]
  • Number of subjects having received IV iron therapy [ Time Frame: Up to End of Treatment (EOT) (Up to week 104) ]
  • Number of Erythropoiesis-Stimulating Agent (ESA)-week dose per subject [ Time Frame: Up to End of Treatment (EOT) (Up to week 104) ]
    1-3 doses of epoetin alfa or beta or biosimilar thereof (in EU) administered within 1 week = 1 ESA-week; 1 darbepoetin SQ or IV dose = 2 ESA-week; 1 Mircera IV or subcutaneous (SQ) dose = 4 ESA-week

  • Change from BL to each post-dosing visit in total cholesterol [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Change from BL to each post-dosing visit in low density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Change from BL to each post-dosing visit in non-HDL cholesterol [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Occurrence of mean LDL cholesterol < 100 mg/dLdL (mean LDL calculated over weeks 12-28 of treatment) [ Time Frame: Up to week 28 ]
  • Occurrence of achieved antihypertensive treatment goal in CKD subjects (SBP < 130 mmHg and DBP < 80 mmHg) based on the mean SBP and mean DBP calculated over weeks 12-28 of treatment with study drug [ Time Frame: Up to week 28 ]
  • Change from BL to the average value in Physical Component Score of SF-36 [ Time Frame: Baseline and weeks 12 to 28 ]
  • Change from BL to the average value in Anemia Subscale ("Additional Concerns") of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score [ Time Frame: Baseline and weeks 12 to 28 ]
  • Change from BL to the average value in Total FACT-An Score [ Time Frame: Baseline and weeks 12 to 28 ]
  • Change from BL to the average value in Health Related Quality of Life Questionnaire consisting of Five Levels (EQ-5D 5) visual analogue scale (VAS) Score [ Time Frame: Baseline and weeks 12 to 28 ]
  • Patients' Global Impression of Change (PGIC) [ Time Frame: Up to End of Treatment (EOT) (Up to week 104) ]
  • Changes from BL to each study visit in hepcidin [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
    Serum hepcidin

  • Changes from BL to each study visit in HbA1c [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
    Hemoglobin A1c glycated hemoglobin (HbA1c) level

  • Time to first occurrence of serum Cr having doubled during study [ Time Frame: Up to End of Study (EOS) (Up to week 108) ]
  • Occurrence of ESRD [ Time Frame: Up to End of Study (EOS) (Up to week 108) ]
    End Stage Renal Disease (ESRD)

  • Safety assessed by nature, frequency, and severity of Adverse Events (AEs) [ Time Frame: Up to End of Study (EOS) (Up to week 108) ]
  • Safety assessed by nature, frequency, and severity of Serious Adverse Events (SAEs) [ Time Frame: Up to End of Study (EOS) (Up to week 108) ]
  • Number of participants with vital signs abnormalities and/or adverse events related to treatment [ Time Frame: Up to End of Study (EOS) (Up to week 108) ]
  • Safety assessed by 12- lead electrocardiogram (ECG) [ Time Frame: Up to End of Study (EOS) (Up to week 108) ]
    Local 12-lead ECGs will be performed on all subjects at specific time points. A single ECG will be taken with the subject in the supine position, after the subject has been lying quietly for 5 minutes

  • Number of participants with laboratory value abnormalities and/or adverse events related to treatment [ Time Frame: Up to End of Study (EOS) (Up to week 108) ]
  • Changes from BL to each study visit in serum ferritin [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Changes from BL to each study visit in Transferrin Saturation (TSAT) [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Changes from BL to each study visit in estimated Glomerular Filtration Rate (eGFR), including eGFR slope over time [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Changes from BL to each study visit in urine albumin/Creatinine (Cr) ratio [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Changes from BL to each study visit in fasting blood glucose [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Change from BL to each post-dosing visit in Apolipoproteins (Apo) A1 [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Change from BL to each post-dosing visit in Apolipoproteins B (ApoB) [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]
  • Change from BL to each post-dosing visit in ApoB/ApoA1 ratio [ Time Frame: Baseline up to End of Study (EOS) (Up to week 108) ]

Enrollment: 597
Actual Study Start Date: September 3, 2013
Estimated Study Completion Date: November 1, 2017
Estimated Primary Completion Date: November 1, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Roxadustat
Study drug will be dosed three times weekly (TIW) during correction period and three times weekly (TIW) during the maintenance period. Dose adjustments will be made during the study
Drug: Roxadustat
tablet
Other Names:
  • ASP1517
  • FG-4592
Placebo Comparator: Placebo
Placebo will be dosed three times weekly (TIW) during correction period and three times weekly (TIW) during the maintenance period. Dose adjustments will be made during the study
Drug: Placebo
tablet

Detailed Description:

The study will consist of three study periods as follows:

  • Screening period: up to 6 weeks.
  • Treatment period: 52 to 104 weeks.
  • Post-Treatment Follow-Up period: 4 weeks
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Subject 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 subject'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.
  • Subject has a ferritin level greater than or equal to 30 ng/mL (greater than or equal to 67.4 pmol/L) at screening.
  • Subject has a transferrin saturation (TSAT) level greater than or equal to 5% at screening.
  • Subject has a serum folate level greater than or equal to lower limit of normal at screening.
  • Subject has a serum vitamin B12 level greater than or equal to lower limit of normal at screening.
  • Subject'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.
  • Subject's body weight is 45.0 kg up to a maximum of 160.0 kg.

Exclusion criteria:

  • Subject has received any ESA treatment within 12 weeks prior to randomization.
  • Subject has had more than one dose of IV iron within 12 weeks prior to randomization.
  • Subject has received a RBC transfusion within 8 weeks prior to randomization.
  • Subject has a known history of myelodysplastic syndrome or multiple myeloma.
  • Subject 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.
  • Subject has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition.
  • Subject has chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
  • Subject is anticipated to have elective surgery that is expected to lead to significant blood loss or anticipated elective coronary revascularization.
  • Subject has active or chronic gastrointestinal bleeding.
  • Subject has received any prior treatment with roxadustat or a hypoxia-inducible factor Prolyl Hydroxylase Inhibitor (HIF-PHI).
  • Subject has been treated with iron-chelating agents within 4 weeks prior to randomization.
  • Subject has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver)
  • Subject has a known New York Heart Association Class III or Intravenous (IV) congestive heart failure.
  • Subject 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.
  • Subject 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.
  • Subject 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.
  • Subject 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).
  • Subject 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.
  • Subject has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration and retinal vein occlusion.
  • Subject has had any prior organ transplant (that has not been explanted) or a scheduled organ transplantation.
  • Subject 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.
  • Subject 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.
  • Subject has a history of alcohol or drug abuse within 2 years prior to randomization.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01887600

  Show 143 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe B.V.
FibroGen
Investigators
Study Chair: Medical Monitor Astellas Pharma Europe B.V.
  More Information

Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT01887600     History of Changes
Other Study ID Numbers: 1517-CL-0608
2012-005180-27 ( EudraCT Number )
Study First Received: June 25, 2013
Last Updated: June 6, 2017

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
anemia
chronic kidney disease (CKD)
Hemoglobin (Hb)
non-dialysis

Additional relevant MeSH terms:
Anemia
Kidney Diseases
Renal Insufficiency, Chronic
Hematologic Diseases
Urologic Diseases
Renal Insufficiency

ClinicalTrials.gov processed this record on August 18, 2017