Safety and Efficacy Study of Roxadustat with compare to Placebo for treatment of Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis

Phase 3

Completed

• Conditions: Chronic kidney disease, unspecified, Male and Female patients ≥ 18 years of age with chronic kidney disease stage 3 to 5 not on dialysis and who have anemia (Hb ≤ 10 g/dL) ,

• Registration Number: CTRI/2015/12/006412
• Lead Sponsor: AstraZeneca AB

Brief Summary

The present randomized double-blind placebo-controlled study objective is to assess the cardiovascular safety and efficacy of Roxadustat in patients with stage 3, 4, or 5 CKD who are anemic and not on dialysis.

Patients will be randomized (1:1) to double-blind treatment with roxadustat or placebo,  TIW and titrated to achieve and maintain Hb 11±1 g/dL. Treatment duration is variable for individual patients (estimated treatment duration 1 to 2 years). A study end date will be declared and common closeout will occur when the target number of CV events has been accrued.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-01
• Study Completion: 2018-09-25
• Last Update Posted: 2020-05-22

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 2600

Inclusion Criteria

• 1.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. 2.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. 3.Transferrin saturation ≥15% at randomization. 4.Serum folate level ≥ lower limit of normal (LLN) at randomization.
• Serum vitamin B12 level ≥LLN at randomization. 5.Alanine aminotransferase and aspartate aminotransferase ≤3 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN at randomization. 6.Body weight 45 to 160 kg.

Exclusion Criteria

• 1.Any erythropoietin analogue treatment within 6 weeks of randomization.
• 2.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.
• 3.History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver).
• 4.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.
• 5.Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis).
• 6.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 scan or magnetic resonance imaging conducted at screening or within 12 weeks prior to randomization.
• 7.Systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥95 mmHg, within 2 weeks prior to randomization.
• Patients may be rescreened once BP controlled.
• 8.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.
• 9.Positive for any of the following: human immunodeficiency virus, hepatitis B surface antigen or anti-hepatitis C virus antibody.
• 10.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.
• 11.Known hemosiderosis, hemochromatosis or hypercoagulable condition.
• 13.Any red blood cell transfusion during the screening period.
• 14.Any current condition leading to active significant blood loss.
• 15.Any treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor.
• 16.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).
• 17.History of alcohol or drug abuse within 2 years prior to randomization.
• 18.Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
• 19.Pregnant or breastfeeding females.
• 21.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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of all-cause mortality, non-fatal myocardial infarction or non-fatal stroke	Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of all-cause mortality, non-fatal myocardial infarction or non-fatal stroke | The number from randomization to the first occurrence of any of the components of the primary composite endpoints.
The number from randomization to the first occurrence of any of the components of the primary composite endpoints.	Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of all-cause mortality, non-fatal myocardial infarction or non-fatal stroke | The number from randomization to the first occurrence of any of the components of the primary composite endpoints.

Secondary Outcome Measures

Name	Time	Method
Proportion of total time of Hb measurements within the interval of 11±1 g/dL	From week 28 until end of study (event-driven, anticipate 1-2 years)
Changes in generic HRQoL as measured by the Short Form 36 (SF-36) (vers 2, standard)	Measured at visit randomization (week 0), week 12, 28 and 52
Change in estimated glomerular filtration rate (eGFR) from baseline to the end of treatment period (event-driven, anticipate 1-2 years)	From baseline to end of study (event-driven, anticipate 1-2 years)
Mean change in hemoglobin (Hb) from baseline to the end of treatment period (event-driven, anticipate 1-2 years)	Baseline to end of study (event-driven, anticipate 1-2 years)
Mean value of all Hb measurements	From week 28 until the end of study will be used.
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)	From the first screening visit to the end of the study (event-driven, anticipate 1-2 years)
Changes in self-reported health status as measured by the EuroQol Health Utility Index-5-dimensional-5-level (EQ-5D-5L) and Patients Global Impression of Change (PGIC).	At baseline, week 12, 28 and 52
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	The number from randomization to the first occurrence of any of the components of the primary composite endpoints.
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)	Measured at visit randomization (week 0), week 12, 28 and 52
Proportion of total time of Hb values within the interval 11±1 g/dL	From week 28 until end of treatment visit

Trial Locations

Locations (25)

Apollo Hospitals; 🇮🇳 Chennai, TAMIL NADU, India

B. J. Medical College & Civil Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

B.J Govt. Medical College & Sassoon General Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Calcutta Medical Research Institute (CMRI); 🇮🇳 Kolkata, WEST BENGAL, India

Care Hospital; 🇮🇳 Nagpur, MAHARASHTRA, India

Christian Medical College & Hospital; 🇮🇳 Vellore, TAMIL NADU, India

Fortis Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Government Medical College (G.M.C); 🇮🇳 Nagpur, MAHARASHTRA, India

JSS Medical College Hospital; 🇮🇳 Mysore, KARNATAKA, India

King George Hospital; 🇮🇳 Visakhapatnam, ANDHRA PRADESH, India

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Apollo Hospitals

🇮🇳Chennai, TAMIL NADU, India

Dr Budithi Subbarao HOD Senior Consultant

Principal investigator

04428296594

nephro.rao@gmail.com