Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by AstraZeneca
Sponsor:
Collaborator:
FibroGen
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02174731
First received: June 24, 2014
Last updated: May 4, 2015
Last verified: May 2015
  Purpose

The purpose of this study is to evaluate the safety and efficacy of roxadustat compare to epoetin alfa for the treatment of anemia in chronic kidney disease patients on dialysis.


Condition Intervention Phase
Anemia
Drug: Roxadustat
Drug: Epoetin alfa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Open-label, Active-Controlled Study of the Safety and Efficacy of Roxadustat in the Treatment of Anemia in Dialysis Patients

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of death from any cause, non-fatal myocardial infarction or non-fatal stroke. [ Time Frame: From randomization (week 0) to end of study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: Yes ]
    The number from randomization to the first occurence of any of the components of the primary composite endpoint.


Secondary Outcome Measures:
  • Mean change in hemoglobin (Hb) from baseline to the end of treatment period (event-driven, anticipate 1-2 years). [ Time Frame: From baseline to end of study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: No ]
    Mean value of all Hb measurements from week 28 until the end of study will be used.

  • Proportion of total time of Hb measurements within the interval of 11±1 g/dL from week 28 until end of treatment visit (event-driven, anticipate 1-2 years). [ Time Frame: From week 28 until end of study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: No ]
    Proportion of total time of Hb values within the interval 11±1 g/dL from week 28 until end of treatment visit.

  • Major adverse CV events+ (MACE+): Time to first occurrence of death from any cause, non-fatal myocardial infarction (MI), non-fatal stroke, heart failure requiring hospitalization or unstable angina leading to hospitalization. [ Time Frame: From randomization (week 0) to end of study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: Yes ]
    Time from randomization to the first occurence of any of the components of the composite endpoint.

  • Time to first occurrence of death from any cause, MI, stroke, heart failure requiring hospitalization, unstable angina leading to hospitalization, vascular access thrombosis, deep vein thrombosis, pulmonary embolism or hypertensive emergency. [ Time Frame: From randomization (week 0) to end of study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: Yes ]
    Time from randomization to the first occurence of any of the components of the composite endpoints.

  • Time to first rescue therapy (composite of erythropoietin analogue therapy [for roxadustat-allocated patients only] or RBC transfusion) [ Time Frame: From randomization (week 0) to end of study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: Yes ]
    Time from randomization to the first occurence of any of the two types of rescue therapy; RBC transfusion or erythropoietin analogue.

  • Changes in self-reported health status as measured by the EuroQol Health Utility Index 5-dimensional-5-level (EQ-5D-5L) during roxadustat or epoetin alfa treatment. [ Time Frame: At baseline, week 12, 28 and 52. ] [ Designated as safety issue: No ]
    The EQ-5D-5L is a self-reported questionnaire measuring utility values.

  • Adverse events (AEs), serious adverse events (SAEs) Changes in vital signs, electrocardiogram (ECG) and laboratory values. Measured at randomization (week 0) to end of study (event-driven, anticipate 1-2 years). [ Time Frame: From the first screening visit to the end of the study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: Yes ]
    Frequencies of AEs and SAEs, and changes in vital signs, ECG and laboratory variables will be evaluated with descriptive statistics.


Estimated Enrollment: 1425
Study Start Date: July 2014
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Roxadustat Drug: Roxadustat
Roxadustat will be administered orally three times a week (TIW) to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL.
Active Comparator: Epoetin alfa Drug: Epoetin alfa
Epoetin alfa will be administered TIW consistent with approved prescribing information for epoetin alfa to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL.

Detailed Description:

This is a Phase 3, multicenter, randomized, open-label, active-controlled study to evaluate the safety and efficacy of roxadustat compared to epoetin alfa for the treatment of anemia in dialysis patients. Patients on hemodialysis (HD) or peritoneal dialysis (PD) who have been treated with an erythropoietin analogue or have an indication for treatment with an erythropoietin analogue will be evaluated for eligibility and randomized at a 1:1 ratio to treatment with roxadustat (with discontinuation of prior erythropoietin analogue therapy) or to an active-control group treated with epoetin alfa.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease at least 30 days prior to visit 1.
  • Two central laboratory hemoglobin values during the screening period, obtained at least 7 days apart, must be <12 g/dL in patients currently treated with an erythropoietin analogue or <10 g/dL in patients not currently treated with an erythropoietin analogue. Patients are considered not currently treated if they have not received either Mircera® for at least 8 weeks or any other erythropoietin analogue for at least 4 weeks prior to visit 1.
  • Ferritin ≥100 ng/mL at randomization.
  • Transferrin saturation (TSAT) ≥20% at randomization.
  • Serum folate level ≥ lower limit of normal (LLN) at randomization.
  • Serum vitamin B12 level ≥LLN at randomization.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN), and total bilirubin ≤1.5 x ULN at randomization.
  • Body weight 45 to 160 kg.

Exclusion criteria:

  • New York Heart Association Class III or intravenous (IV) congestive heart failure at enrollment
  • Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
  • History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver).
  • 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 chronic kidney disease (CKD).
  • Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis).
  • Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category II F, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. computerized tomography (CT) scan or magnetic resonance imaging (MRI)) conducted at screening or within 12 weeks prior to randomization.
  • Uncontrolled hypertension at the time of randomization, (defined as systolic BP ≥180 mmHg or diastolic BP ≥100 mmHg on repeated measurement post-dialysis in hemodialysis patients or at any time in peritoneal dialysis patients), contraindication to epoetin alfa treatment (e.g., pure red cell aplasia, hypersensitivity or know inability to tolerate epoetin alfa).
  • 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.
  • Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody.
  • Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be principal cause of anemia.
  • Known hemosiderosis, hemochromatosis or hypercoagulable condition.
  • Any prior organ transplant with the exception of a renal transplant that was subsequently removed ("explanted") or scheduled organ transplantation date.
  • Any red blood cell (RBC) transfusion during the screening period.
  • Any current condition leading to active significant blood loss.
  • Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).
  • History of alcohol or drug abuse within 2 years prior to randomization
  • Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
  • Pregnant or breastfeeding females.
  • Known allergy to the investigational product or any of its ingredients.
  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: NCT02174731

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Urban Olsson, PhD D5740C00002-ESRD@astrazeneca.com

  Show 198 Study Locations
Sponsors and Collaborators
AstraZeneca
FibroGen
Investigators
Principal Investigator: Geoffrey Block, MD Denver Nephrologists, PC
Study Director: Nicolas Guzman, MD AZ R&D, Gaithersburg
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02174731     History of Changes
Other Study ID Numbers: D5740C00002
Study First Received: June 24, 2014
Last Updated: May 4, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Renal,
CKD,
Epoetin alfa,
Roxadustat,
dialysis,
anemia

Additional relevant MeSH terms:
Anemia
Hematologic Diseases
Epoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on June 30, 2015