CTRI/2015/12/006461 [Registered on: 23/12/2015] Trial Registered Prospectively
Last Modified On:
27/05/2020
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis
Scientific Title of Study
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
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
D5740C00002
Protocol Number
NCT02174731
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Country Head - Site Management and Monitoring – India
Affiliation
AstraZeneca Pharma India Ltd, Bangalore
Address
AstraZeneca Pharma India Ltd.
Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road,
Bangalore KARNATAKA 560024 India
Phone
09535104975
Fax
00918067748857
Email
tapankumar.shah@astrazeneca.com
Details of Contact Person Public Query
Name
Mr Tapankumar Shah
Designation
Country Head, Clinical Operations
Affiliation
AstraZeneca Pharma India Ltd., Bangalore
Address
AstraZeneca Pharma India Ltd.
Bangalore KARNATAKA 560024 India
Phone
00918067748006
Fax
00918023622015
Email
Tapankumar.Shah@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB, 151 85 Södertälje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Södertälje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Countries of Recruitment
Argentina Australia Brazil Bulgaria Canada Czech Republic Hungary India Mexico Peru Philippines Poland Romania Russian Federation Slovakia Spain Sweden Thailand Ukraine United States of America Viet Nam
Institutional Ethics Committee of BJ Govt. Medical College and Sassoon Government Hospital, Dept. of Pharmacology, BJ Govt. Medical College, Sassoon Road, Pune - 411001
Approved
Institutional Ethics Committee of Topiwala National Medical College and BYL Nair Charitable Hospital G Building Ground Floor, Dr A.L Nair Road, Mumbai Central ,Mumbai-400008
Approved
Institutional Ethics Committee Siddharatha Medical College & Govt General Hospital (IEC SMC & GGH) Near Dr.NTR Health University Gunadala, Vijayawada – 520008 Andhra Pradesh, India
Approved
Institutional Ethics Committee, Max Healthcare Super Speciality Hospital, 6th floor, 2, Press Enclave Road, Saket, New Delhi-110017
Approved
Muljibhai Patel Society for Research in Nephro. Urology Ethics Committee (MPSRNUEC) Dr. Virendra Desai Road, Nadiad – 387 001 Gujarat – India
Approved
Sir Ganga Ram Hospital Ethics Committee, Room No 1496. IV Floor , Old Building , Sir Ganga Ram Hospital , Old Rajinder Nagar ,New Delhi-110060
Approved
The Chairperson, Institutional Ethics Committee, The Calcutta Medical Research Institute, 7/2, Diamond Harbour Road, Kolkata – 27, India
(1) ICD-10 Condition: N186||End stage renal disease, Male and Female patients ≥ 18 years of age with chronic kidney disease treated with dialysis, who have anemia (Hb ≤ 10 g/L),
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
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.
Intervention
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.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease at least 30 days prior to visit 1.
2. 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.
3. Ferritin ≥100 ng/mL at randomization.
4. Transferrin saturation (TSAT) ≥20% at randomization.
5. Serum folate level ≥ lower limit of normal (LLN) at randomization.
6. Serum vitamin B12 level ≥LLN at randomization.
7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN), and total bilirubin ≤1.5 x ULN at randomization.
8. Body weight 45 to 160 kg.
ExclusionCriteria
Details
1. New York Heart Association Class III or intravenous (IV) congestive heart failure at enrollment
2. 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.
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 chronic kidney disease (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 (CT) scan or magnetic resonance imaging (MRI)) conducted at screening or within 12 weeks prior to randomization.
7. 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).
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 (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody.
10. 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.
11. Known hemosiderosis, hemochromatosis or hypercoagulable condition.
12. Any prior organ transplant with the exception of a renal transplant that was subsequently removed ("explanted") or scheduled organ transplantation date.
13. Any red blood cell (RBC) transfusion during the screening period.
14. Any current condition leading to active significant blood loss.
15. Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).
16. History of alcohol or drug abuse within 2 years prior to randomization
17. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
18. Pregnant or breastfeeding females.
19. Known allergy to the investigational product or any of its ingredients.
Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of death from any cause, 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 endpoint
Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of death from any cause, 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 endpoint
Secondary Outcome
Outcome
TimePoints
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.
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)
Proportion of total time of Hb values within the interval 11±1 g/dL
From week 28 until end of treatment visit.
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.
From randomization (week 0) to end of study (event-driven, anticipate 1-2 years)
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.
From randomization (week 0) to end of study (event-driven, anticipate 1-2 years).
Time to first rescue therapy (composite of erythropoietin analogue therapy [for roxadustat-allocated patients only] or RBC transfusion)
From randomization (week 0) to end of 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) during roxadustat or epoetin alfa treatment.
At baseline, week 12, 28 and 52
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)
From the first screening visit to the end of the study (event-driven, anticipate 1-2 years
Target Sample Size
Total Sample Size="1425" Sample Size from India="100" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
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