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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02174627
• 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 (CKD), Not on Dialysis
• Scientific 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
• Date of first enrolment: June 26, 2014
• Target sample size: 2781
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02174627
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Bulgaria, Canada, Colombia, Czech Republic, Czechia, Germany, Hungary, India, Italy, Korea, Republic of, Malaysia, Mexico, Peru, Philippines, Poland, Puerto Rico, Romania, Russian Federation, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, 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. eGFR <60 mL/min/1.73 m2, (calculated by central lab) corresponding to stage 3, 4 or
5CKD according to the Kidney Disease Outcomes Quality Initiative (KDOQI), not
receiving dialysis

4. Mean of 2 most recent central laboratory Hb values during the screening period,
obtained at least 7 days apart, must be <10.0 g/dL

5. Ferritin =50 ng/mL at randomization (obtained from screening visit)

6. TSAT =15 % 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) =3 x 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

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 randomization in the present study

3. Any erythropoietin analogue treatment within 6 weeks of randomization

4. New York Heart Association Class III or IV congestive heart failure at enrollment

5. Myocardial infarction (MI), acute coronary syndrome, stroke, seizure or a
thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism)
within 12 weeks prior to randomization

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

7. 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

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

9. 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

10. Systolic BP =160 mmHg or diastolic BP =95 mmHg (confirmed by repeated measurement),
within 2 weeks prior to randomization. Patients may be rescreened once BP controlled

11. 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

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

13. Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus
erythematosus (SLE), ankylosing spondylitis, psoriatic arthritis or inflammatory bowel
disease that is determined to be the principal cause of anemia

14. Known hemosiderosis, hemochromatosis or hypercoagulable condition

15. Any prior organ transplant or a scheduled organ transplantation date

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

17. Any current condition leading to active significant blood loss

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

19. 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 IP in this
study. (Note: patients consented and screened, but not randomized in this study or a
previous study are not excluded)

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

21. Females of childbearing potential, unless using contraception as detailed in the
protocol or sexual abstinence

22. Pregnant or breastfeeding females

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

24. 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: Placebo

Primary Outcome(s)

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

Secondary Outcome(s)

Proportion of Total Time of Interpolated Hb Values Greater Than or Equal To 10 g/dL From Week 28 to Week 52 [Time Frame: Week 28 up to Week 52.]

Time-To-First Instance of Receiving IV Iron, RBC Transfusion or Erythropoietin Analogue as Rescue Therapy [Time Frame: Baseline (Day1, Week 0) up to End of Study (EOS) visit (4 weeks after the treatment period) (or up to date of first rescue therapy), with treatment duration up to 4 years.]

Annual Rate of eGFR Change From Baseline Prior to the Initiation of Dialysis or Kidney Transplant [Time Frame: Baseline (Day1, Week 0) up to EOS visit (4 weeks after the treatment period), with treatment duration up to 4 years.]

Mean Change From Baseline in SF-36 Physical Functioning Sub-Score From Week 12 to Week 28 [Time Frame: Baseline (Day 1, Week 0) and Week 12 to Week 28.]

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

Mean Change From Baseline in Short Form 36 (SF-36) Vitality Sub-Score From Week 12 to Week 28 [Time Frame: Baseline (Day 1, Week 0) and Week 12 to Week 28.]

Percentage of Participants With Hb Response During the First 24 Weeks of Treatment [Time Frame: Baseline (Day 1, Week 0) up to Week 24.]

Time-To-First Instance of Receiving a RBC Transfusion As Rescue Therapy [Time Frame: Baseline (Day1, Week 0) up to EOS visit (4 weeks after the treatment period) (or up to date of first RBC rescue therapy), with treatment duration up to 4 years.]

Mean Change From Baseline in Hb Averaged Over 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) and Week 28 to Week 52.]

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

Secondary ID(s)

D5740C00001

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/NCT02174627