Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis.

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by AstraZeneca
Sponsor:
Collaborator:
FibroGen
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02174627
First received: June 24, 2014
Last updated: September 30, 2014
Last verified: September 2014
  Purpose

The purpose of the study is to evaluate the safety and efficacy of roxadustat for treatment of anemia in patients with chronic kidney disease not on dialysis.


Condition Intervention Phase
Anemia
Drug: Roxadustat
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy 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 AstraZeneca:

Primary Outcome Measures:
  • Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of all cause mortality, 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 endpoints.


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.

  • MACE+: Time to first occurrence of all cause mortality, non-fatal myocardial infarction (MI) or 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 ]
    The number from randomization to the first occurence of any of the components of the primary composite endpoints.

  • Time to first occurrence of all cause mortality, MI, stroke, heart failure requiring hospitalization, unstable angina leading to hospitalization, deep vein thrombosis, pulmonary embolism, vascular access thrombosis or hypertensive emergency. [ 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 endpoints.

  • Time-to-first instance of receiving intravenous (IV) iron, red blood cell (RBC) transfusions or erythropoietin analogue as rescue therapy. [ Time Frame: From randomization (week 0) to end of study (event-driven, anticipate 1-2 years). ] [ Designated as safety issue: Yes ]
    The time from randomization to the first occurence of any of the components of the primary composite endpoints.

  • Change in estimated glomerular filtration rate (eGFR) 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 ]
    Analysis of changes in eGFR.

  • Changes in anemia symptoms and four disease-specific Health Related Quality of Life (HRQoL) domains as measured by the Functional Assessment of Cancer Therapy-Anemia (FACT-An). [ Time Frame: Measured at visit randomization (week 0), week 12, 28 and 52. ] [ Designated as safety issue: No ]
    The FACT-An has a recall period of the 'past seven days'. Respondents are asked to provide responses (i.e. 'Not at all', 'A little bit', 'Somewhat', 'Quite a bit' and 'Very much'), to a list of statements which are either positively or negatively phrased. For all FACT-An scales, a higher score indicates better HRQoL.

  • Changes in generic HRQoL as measured by the Short Form 36 (SF-36) (vers 2, standard). [ Time Frame: Measured at visit randomization (week 0), week 12, 28 and 52 ] [ Designated as safety issue: No ]
    The SF-36 version 2, standard is a general HRQoL instrument designed to assess generic health concepts relevant across age, disease and treatment groups.

  • Changes in self-reported health status as measured by the EuroQol Health Utility Index (EQ-5D-5L) and Patients' Global Impression of Change (PGIC). [ Time Frame: At baseline, week 12, 28 and 52. ] [ Designated as safety issue: No ]
    Analysis of changes in the self-reported health status.

  • Adverse events (AEs), serious adverse events (SAEs) and changes in vital signs, electrocardiogram (ECG) and laboratory values. Measured from first screening visit 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: 2600
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
The initial study drug dose is 70 mg three times a week (TIW). The dose is subsequently adjusted to achieve and maintain Hb 11±1 g/dL.
Placebo Comparator: Placebo Drug: Placebo
The initial study drug dose is 70 mg three times a week (TIW). The dose is subsequently adjusted to achieve and maintain Hb 11±1 g/dL.

Detailed Description:

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in anemic patients with Stage 3, 4 or 5 chronic kidney disease (CKD) who are not on dialysis.

  Eligibility

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

Inclusion Criteria:

  • A glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, corresponding to stage 3, 4 or 5 chronic kidney disease (CKD) according to the Kidney Disease Outcomes Quality Initiative, not receiving dialysis.
  • Mean of 2 most recent central laboratory hemoglobin (Hb) values during the screening period, obtained at least 7 days apart, must be <10.0 g/dL.- Ferritin ≥50 ng/mL at randomization.
  • Transferrin saturation ≥15% at randomization.
  • Serum folate level ≥ lower limit of normal (LLN) at randomization. - Serum vitamin B12 level ≥LLN at randomization.
  • Alanine aminotransferase and aspartate aminotransferase ≤3 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN at randomization.
  • Body weight 45 to 160 kg.

Exclusion Criteria:

  • Any erythropoietin analogue treatment within 6 weeks of randomization.
  • New York Heart Association Class III or IV congestive heart failure at enrollment- Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/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 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 IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. computerized tomography scan or magnetic resonance imaging conducted at screening or within 12 weeks prior to randomization.
  • Systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥95 mmHg, within 2 weeks prior to randomization. Patients may be rescreened once BP controlled.
  • 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, hepatitis B surface antigen or anti-hepatitis C virus antibody.
  • Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia.
  • Known hemosiderosis, hemochromatosis or hypercoagulable condition.
  • Any prior organ transplant or a scheduled organ transplantation date.
  • Any red blood cell transfusion during the screening period.
  • Any current condition leading to active significant blood loss.
  • Any treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor.
  • Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 1 month of the first administration of investigation product in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded).
  • 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.
  • Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound safety or efficacy assessment or may interfere with study participation.
  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: NCT02174627

Contacts
Contact: Urban Olsson, PhD +46 31 7762373 ClinicalTrialTransparency@astrazeneca.com
Contact: Lisa Jacobsson, MSc D5740C00001-CKD@astrazeneca.com

  Show 49 Study Locations
Sponsors and Collaborators
AstraZeneca
FibroGen
Investigators
Principal Investigator: Steven Fishbane, MD Chief Division of Kidney Diseases and Hypertension, Great Neck, USA
Study Director: Nicolas Guzman, MD AZ R&D Gaithersburg
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02174627     History of Changes
Other Study ID Numbers: D5740C00001
Study First Received: June 24, 2014
Last Updated: September 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Renal,
CKD,
Roxadustat,
anemia,
non-dialysis

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

ClinicalTrials.gov processed this record on October 21, 2014