Anemia in Chronic Kidney Disease patients not on Dialysis
Conditions
Interventions
The Treatment Period consists of a Correction Period and a Maintenance Period.
Subjects are
randomized to 1 of 4 Treatment Arms (2:2:2:3 ratio) as illustrated in the table
below. The
randomization w
Sponsors
Astellas Pharma
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subject is eligible for the study if all of the following apply: 1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations has been obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject age is >= 18 years. 3. Subject has a diagnosis of CKD, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not on dialysis; with an eGFR = lower limit of normal (LLN). 9. Subject has a serum vitamin B12 level >=LLN. 10. Subject*s alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are <=3 x upper limit of normal (ULN), and total bilirubin (TBL) is <=1.5 x ULN. 11. Subject*s body weight is 45.0 kg to a maximum of 160.0 kg. 12. Female subject is either: Of non-child bearing potential: - post-menopausal (defined as at least 1 year without any menses) prior to Screening, or - documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening). Or, of child bearing potential: - If of childbearing potential must have a negative serum pregnancy test at Screening and must use two forms of birth control* (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days after final study treatment administration. 13. Female subject must not be breastfeeding at Screening or throughout the study period, and for 28 days after the final study treatment administration. 14. Female subject must not donate ova starting at Screening and throughout the study period and for 28 days after final study drug administration. 15. Male subject and their female spouse/partner(s) who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control* (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 12 weeks after final study treatment administration. *Acceptable forms of birth control include: - Established use of oral, injected or implanted hormonal methods of contraception. - Placement of an intrauterine device (IUD) or intrauterine system (IUS) - Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository (if a
Exclusion criteria
Exclusion criteria: Subject will be excluded from participation if any of the following apply: 1. Subject has received any ESA treatment within 12 weeks prior to randomization. 2. Subject has received any dose of IV iron within 6 weeks prior to randomization. 3. Subject has received a Red Blood Cell (RBC) transfusion within 8 weeks prior to randomization. 4. Subject has a known history of myelodysplastic syndrome or multiple myeloma. 5. Subject has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD. 6. Subject has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition. 7. Subject has a known chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission. 8. Subject is anticipated to undergo elective surgery that is expected to lead to significant blood loss during the study period or anticipated elective coronary revascularization. 9. Subject has active or chronic gastrointestinal bleeding. 10. Subject has received any prior treatment with FG-4592 or a hypoxia-inducible factor prolyl hydroxylase inhibitor. 11. Subject has been treated with iron-chelating agents within 4 weeks prior to randomization. 12. Subject has a history of chronic liver disease (e.g. cirrhosis or fibrosis of the liver). 13. Subject has known New York Heart Association Class III or IV congestive heart failure. 14. Subject has had a 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. 15. Subject has one or more contraindications for treatment with darbepoetin alfa: * Uncontrolled hypertension in the opinion of the investigator, or two or more blood pressure values of systolic blood pressure (SBP) >=160 mmHg or diastolic blood pressure (DBP) >=95mm Hg, within 2 weeks prior to randomization. * Known hypersensitivity to darbepoetin alfa, recombinant human erythropoietin, or any of the excipients. 16. Subject has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma as shown on renal ultrasound within 12 weeks prior to randomization. 17. Subject has a history of malignancy, except for 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. 18. Subject is positive for any of the following: * human immunodeficiency virus (HIV). * hepatitis B surface antigen (HBsAg). * or anti-hepatitis C virus antibody (anti-HCV Ab). 19. Subject has an active clinically significant infection that is manifested by White Blood Count (WBC) >ULN, and/or fever, in conjunction with clinical signs or symptoms of infection within two weeks prior to randomization. 20. Subject has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration or retinal vein occlusion. 21. Subject has had any prior organ transplant (that has not been explanted), subject is scheduled for organ transplantation, or subject is likely to initiate renal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy variable is: * Hb response defined as: Hb >=11.0 g/dL and a Hb increase from BL Hb by >=1.0 g/dL in any subject with BL Hb>8.0 g/dL, OR an increase from BL Hb by >=2.0 g/dL in any subject with BL Hb | — |
Secondary
| Measure | Time frame |
|---|---|
| - Hb change from BL to the average Hb of weeks 28 to 36, without having received rescue therapy (i.e. RBC transfusion for all subjects, or darbepoetin alfa for FG-4592 treated subjects) within 6 weeks prior to and during this 8-week evaluation period. - Change from BL in Low-Density Lipoprotein (LDL) cholesterol to the average LDL cholesterol of weeks 12 to 28. - Mean monthly IV iron use (mg) per subject during weeks 1 to 36 (monthly defined as a period of 4 weeks). - Change from BL in SF-36 Physical Functioning (PF) sub-score to the average PF sub-score of weeks 12 to 28 - Change from BL in SF-36 Vitality (VT) sub-score to the average VT subscore of weeks 12 to 28 - Blood pressure effect: o Change from BL in mean arterial pressure (MAP) to the average MAP value of weeks 20 to 28. o Occurrence and time to occurence of hypertension (defined as either systolic blood pressure [SBP] >170 mmHg AND an increase from BL of >=20 mmHg SBP or diastolic blood pressure [DBP] >110 mmHg AND an increase from BL of >=15 mmHg DBP on 2 consecutive visits) during weeks 1 to 36. - Change from BL in SF-36 Physical Functioning (PF) sub-score to the average PF sub-score of weeks 12 to 28. - Change from BL in SF-36 Vitality (VT) sub-score to the average VT sub-score of weeks 12 to 28. | — |
Countries
Netherlands
Outcome results
None listed