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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02174731
• Date of registration: 24/06/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis.
• Scientific 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
• Date of first enrolment: July 1, 2014
• Target sample size: 2133
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02174731
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, Canada, Czech Republic, Czechia, Hungary, India, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Thailand, Ukraine, United States, Vietnam

Contacts

• Name: Steven Fishbane, MD
• Affiliation: Chief Division of Kidney Diseases and Hypertension, North Shore University Hospital, Great Neck, NY, USA

• Name: Mark Houser, MD
• Affiliation: AZ R&D, Gaithersburg, USA

Key inclusion & exclusion criteria

Inclusion criteria:

1. Provision of Informed Consent prior to any study specific procedures

2. Age =18 years at screening visit 1

3. Previous versions of the protocol prior to US amendment ver 6.0 and outside of US
amendment ver 7.0:

Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native
kidney end-stage renal disease (ESRD) at least 30 days prior to visit 1. Patients
treated with hemodialysis must have access consisting of an arteriovenous fistula, AV
graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a
functioning peritoneal dialysis catheter in place.

Starting with US amendment ver. 6.0 and outside of US amendment ver 7.0 (changed to
recruit incident dialysis patients only):

Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native
kidney end-stage renal disease (ESRD) for a minimum of 2 weeks and a maximum of 4
months prior to randomization. Patients treated with hemodialysis must have access
consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter.
Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter
in place.

4. Two central laboratory Hb 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.

5. Ferritin =100 ng/mL at randomization (obtained from screening visit)

6. TSAT =20% at randomization (obtained from screening visit)

7. Serum folate level = lower limit of normal (LLN) at randomization (obtained from
screening visit)

8. Serum vitamin B12 level = LLN at randomization (obtained from screening visit)

9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3x upper limit of
normal (ULN), and total bilirubin (Tbili) =1.5 x ULN at randomization (obtained from
screening visit)

10. Body weight 45 to 160 kg (prescribed dry weight)

Exclusion criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site)

2. Previous randomisation in the present study

3. New York Heart Association Class III or IV congestive heart failure at enrolment

4. 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

5. History of chronic liver disease (e.g., chronic infectious hepatitis, chronic
auto-immune liver disease, cirrhosis or fibrosis of the liver)

6. 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

7. Known and untreated retinal vein occlusion or known and untreated proliferative
diabetic retinopathy (risk for retinal vein thrombosis)

8. 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. CT scan
or MRI) conducted at screening or within 12 weeks prior to randomization.

9. 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)

10. 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.

11. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B
surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab)

12. Chronic inflammatory diseases such as rheumatoid arthritis, SLE, ankylosing
spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to
be the principal cause of anemia

13. Known hemosiderosis, hemochromatosis or hypercoagulable condition

14. Any prior organ transplant with the exception of an autologous renal transplant or a
renal transplant that was subsequently removed ("explanted") or scheduled organ
transplantation date

15. Any red blood cell (RBC) transfusion during the screening period

16. Any current condition leading to active significant blood loss

17. Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase
inhibitor (HIF-PHI)

18. 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 the month preceding the first administration of IP in this
study. (Note: patients consented and screened, but not randomized in this study or a
previous study are not excluded)

19. History of alcohol or drug abuse within 2 years prior to randomization

20. Females of childbearing potential, unless using contraception as detailed in the
protocol or sexual abstinence (see Section 3.8)

21. Pregnant or breastfeeding females

22. Known allergy to the investigational product or any of its ingredients

23. 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 efficacy or safety assessment, or may interfere with study
participation



Age minimum: 18 Years
Age maximum: 130 Years
Gender: All

Health Condition(s) or Problem(s) studied

Anemia

Intervention(s)

Drug: Roxadustat

Drug: Epoetin alfa

Primary Outcome(s)

Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 [Time Frame: Baseline (Day 1, Week 0), Week 28 to 52]

Secondary Outcome(s)

Change in Hb From Baseline to the Mean Level During the Evaluation Period (Week 28 to Week 36) Without Having Received Rescue Therapy Within 6 Weeks Prior to and During the 8-Week Evaluation Period [Time Frame: Baseline (Day 1, Week 0), Week 28 to 36]

Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24 [Time Frame: Baseline (Day 1, Week 0) to Week 24]

Proportion of Total Time of Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 52 [Time Frame: Week 28 to 52]

Time-To-First Administration of RBC Transfusion as Rescue Therapy [Time Frame: Baseline (Day 1, Week 0) up to EOS (4 weeks after the treatment period)]

Mean Change in Hb From Baseline to the Participant's Mean Level Between Week 28 to Week 52 in Participants With Baseline High-Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN) [Time Frame: Baseline (Day 1, Week 0), Week 28 to 52]

Mean Monthly IV Iron Use From Week 36 to End of Study (EOS) [Time Frame: Week 36 to EOS (4 weeks after the treatment period)]

Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52 [Time Frame: Week 28 to 52]

Secondary ID(s)

D5740C00002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

FibroGen

Results

• Results available: Yes
• Date Posted: 16/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02174731