Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With CKD on Dialysis

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02174731
First received: June 24, 2014
Last updated: August 13, 2014
Last verified: August 2014
  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
Chronic Kidney Disease
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 6) 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 primary composite endpoint.


Secondary Outcome Measures:
  • Mean change in hemoglobin (Hb) from baseline to the end of treatment (EOT) period (~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 (~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 weeks 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 6) 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 primary composite endpoint.

  • Time to first occurrence of death from any cause, non-fatal MI, non-fatal stroke, heart failure requiring hospitalization, unstable angina leading to hospitalization, vascular access thrombosis, deep vein thrombosis or pulmonary embolism. [ Time Frame: From randomization (~week 6) 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 primary composite endpoints.

  • Changes in self-reported health status as measured by the EuroQol Health Utility Index five-dimensional five-level (EQ-5D-5L) during Roxadustat or EPO treatment. Measured at baseline, week 12, 28 and 52. [ 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.

  • Time-to-first rescue therapy (composite) of intravenous (IV) iron, red blood cell (RBC) transfusion, or recombinant erythropoietin (for Roxadustat patients only) as rescue therapy. [ Time Frame: From randomization (~week 6) 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 three types of rescue therapy; IV iron, RBC transfusion, or EPO.

  • Adverse events (AEs), serious adverse events (SAEs) Changes in vital signs, electrocardiogram (ECG) and laboratory values. Measured at randomization (~week 6) to end of study (event-driven, anticipate 1-2 years). [ Time Frame: From randomization (~week 6) to end of study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of Roxadustat.


Estimated Enrollment: 2850
Study Start Date: June 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 and maintain an Hb level of 11 g/dL.
Active Comparator: Epoetin alfa Drug: Epoetin alfa
EPO will be administered TIW consistent with approved prescribing information for epoetin alfa to achieve and maintain an Hb level of 11g/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 (EPO) for the treatment of anemia in dialysis patients. Patients on hemodialysis (HD) or peritoneal dialysis (PD) who have been treated with a recombinant erythropoietin or have an indication for treatment with a recombinant erythropoietin will be evaluated for eligibility and randomized at a 1:1 ratio to treatment with Roxadustat (with discontinuation of prior recombinant erythropoietin therapy) or to an active-control group treated with EPO.

  Eligibility

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

Inclusion criteria:

  • Age ≥18 years
  • Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease at least 30 days prior to visit 1.
  • Mean of 2 central laboratory Hb values during the screening period, obtained at least 7 days apart, must be ≤12.0 g/dL in patients currently treated with a recombinant erythropoietin or <10 g/dL in patients not currently treated with a recombinant erythropoietin. Patients are considered not currently treated if they have not received either Mircera® for at least 8 weeks or any other recombinant erythropoietin for at least 4 weeks prior to visit 1.
  • Ferritin ≥50 ng/mL at randomization.
  • Transferrin saturation (TSAT) ≥10% 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:

  • Current treatment with an average weekly dose of epoetin alfa or epoetin beta exceeding 18,000 IU, current treatment with an average weekly dose of darbepoetin exceeding 90 μg/week or current treatment with Mircera® at an average monthly dose exceeding 225 μg/month.
  • New York Heart Association Class III or intravenous (IV) congestive heart failure at enrollment
  • Myocardial infarction, acute coronary syndrome, stroke, seizure or a thromboembolic 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, 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, history of seizure or any other contra-indication 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.
  • 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.
  • 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: Sara V Samuelsson, MSc +46 31 7064414 ClinicalTrialTransparency@astrazeneca.com
Contact: Lisa Jacobsson, Msc lisa.jacobsson@astrazencea.com

Locations
United States, California
Research Site Not yet recruiting
Los Angeles, California, United States
United States, Colorado
Research Site Recruiting
Denver, Colorado, United States
United States, New York
Research Site Not yet recruiting
Great Neck, New York, United States
United States, Texas
Research Site Not yet recruiting
San Antonio, Texas, United States
Bulgaria
Research Site Not yet recruiting
Botevgrad, Bulgaria
Research Site Not yet recruiting
Dupnitsa, Bulgaria
Research Site Not yet recruiting
Haskovo, Bulgaria
Research Site Not yet recruiting
Kyustendil, Bulgaria
Research Site Not yet recruiting
Razlog, Bulgaria
Research Site Not yet recruiting
Samokov, Bulgaria
Research Site Not yet recruiting
Sandanski, Bulgaria
Research Site Not yet recruiting
Silistra, Bulgaria
Research Site Not yet recruiting
Sliven, Bulgaria
Research Site Not yet recruiting
Smolyan, Bulgaria
Research Site Not yet recruiting
Targovishte, Bulgaria
Research Site Not yet recruiting
Yambol, Bulgaria
Peru
Research Site Not yet recruiting
Lima, Peru
Research Site Not yet recruiting
San Isidro, Peru
Russian Federation
Research Site Not yet recruiting
Irkutsk, Russian Federation
Research Site Not yet recruiting
Nizhny Novgorod, Russian Federation
Sweden
Research Site Not yet recruiting
Stockholm, Sweden
Research Site Not yet recruiting
Örebro, Sweden
Sponsors and Collaborators
AstraZeneca
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: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Renal,
CKD,
EPO,
Roxadustat,
dialysis,
anemia

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014