Anemia due to end-stage renal disease in incident-dialysis patients. MedDRA version: 16.1 Level: LLT Classification code 10054606 Term: Secondary anemia System Organ Class: 100000004851
Conditions
Interventions
Product Name: FG-4592
Product Code: FG-4592
Pharmaceutical Form: Tablet
INN or Proposed INN: FG-4592
CAS Number: 808118-40-3
Current Sponsor code: FG-4592
Other descriptive name: FG-4592
Concentration
Sponsors
FibroGen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years. 2. Subject has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines. 3. Receiving hemodialysis or peritoneal dialysis for native kidney end-stage renal disease (ESRD) for a minimum of 2 weeks and a maximum of 4 months, prior to randomization. 4. Hemodialysis access consisting of an arteriovenous (AV) fistula, AV graft, or tunnelled (permanent) catheter; or Peritoneal dialysis catheter in use. 5. Mean of the three most recent Hb values during the Screening Period, obtained at least 4 days apart, must be =10.0 g/dL, with a difference of =1.3 g/dL between the highest and the lowest values. The last Hb value must be drawn within 10 days prior to randomization. 6. Ferritin =50 ng/mL. 7. TSAT =10%. 8. Serum folate level, performed within 8 weeks prior to randomization = lower limit of normal (LLN). 9. Serum vitamin B12 level, performed within 8 weeks prior to randomization = LLN. 10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =3x upper limit of normal (ULN), and total bilirubin (Tbili)=65 years) yes F.1.3.1 Number of subjects for this age range 750
Exclusion criteria
Exclusion criteria: 1. Any ESA treatment within 12 weeks prior to randomization. 2. More than one dose of IV iron within 4 weeks prior to randomization. 3. RBC transfusion within 8 weeks prior to randomization. 4. Active, clinically significant infection that could be manifested by white blood cell (WBC) count >ULN, and/or fever, in conjunction with clinical signs or symptoms of infection. 5. History of chronic liver disease (e.g. chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis, or fibrosis of the liver). 6. New York Heart Association Class III or IV congestive heart failure. 7. Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization. 8. Uncontrolled hypertension, in the opinion of the investigator, (e.g. that requires change in anti-hypertensive medication) within 2 weeks prior to randomization. 9. Renal ultrasound performed within 12 weeks prior to randomization indicative of a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma. 10. 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. 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 disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission. 13. Known, untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration, or retinal vein occlusion. 14. Known history of myelodysplastic syndrome or multiple myeloma. 15. Known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than chronic kidney disease (CKD). 16. Known hemosiderosis, hemochromatosis, coagulation disorder, or a hypercoagulable condition. 17. Any prior organ transplant (that has not been explanted), or a scheduled organ transplantation. 18. Anticipated elective surgery, except for vascular access surgery or dialysis catheter placement, that is expected to lead to significant blood loss, or anticipated elective coronary revascularization. 19. Known, active or chronic gastrointestinal bleeding. 20. Any prior treatment with FG-4592 or a HIF prolyl hydroxylases (HIF-PHI). 21. Use of iron-chelating agents within 4 weeks prior to randomization. 22. Known hypersensitivity reaction to any ESA. 23. Use of an investigational drug or treatment, participation in an investigational study, or presence of an expected carryover effect of an investigational treatment, within 4 weeks prior to randomization. 24. Anticipated use of dapsone in any dose amount or chronic use of acetaminophen or paracetamol >2.0 g/day during the treatment or follow-up periods of the study. 25. History of alcohol or drug abuse within 2 years prior to randomization. 26. Females of childbearing potential, unless using contraception as detailed in the protocol; male subjects with sexual partners of childbearing potential who are not on birth control unless the male subject agrees to use contraception. 27. Pregnant or breastfeeding females. 28. Any m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: After the first 24 weeks of treatment.;Main Objective: Evaluate the efficacy and safety of FG-4592 in the treatment of anemia in incident-dialysis subjects compared to Active Control.;Secondary Objective: - Evaluate the efficacy of FG-4592 in the maintenance of hemoglobin (Hb) compared to Active Control. - Evaluate the utilization of intravenous (IV) iron with FG-4592 compared to Active Control. - Evaluate effect of FG-4592 on serum lipid parameters compared to Active Control. - Evaluate the effect of FG-4592 on blood pressure (BP) compared to Active Control. - Evaluate time to achieve hemoglobin (Hb) response compared to Active Control. - Evaluate health-related quality of life (HRQoL) benefit of FG-4592;Primary end point(s): The proportion of subjects who achieve a Hb response at two consecutive visits during the first 24 weeks of treatment, without rescue therapy within 6 weeks prior to the Hb response. A Hb response is defined, using central laboratory values, as : - Hb =11.0 g/dL and a Hb increase from baseline by =1.0 g/dL in subjects whose baseline Hb >8.0 g/dL, or - Increase in Hb =2.0 g/dL in subjects whose baseline Hb =8.0 g/dL. Rescue therapy for FG-4592 treated subjects is defined as ESA rescue or RBC transfusion, and rescue therapy for Epoetin alfa treated subjects is defined as RBC transfusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Hemoglobin maintenance: Mean change in Hb averaged over 8 weeks of treatment at Weeks 28-36, without rescue therapy within 6 weeks prior to and during this 8-week evaluation period. - Mean change in low-density lipoprotein (LDL) cholesterol averaged over Weeks 12-24. - Average monthly IV iron use per subject during the Treatment Period. - Blood pressure effects: - Proportion of patients with exacerbation of hypertension, meeting at least one of the following criteria: - increase in anti-hypertensive medication use, - adverse event of hypertension, or - increase in blood pressure: An increase from baseline of = 20 mm Hg systolic BP and sBP >170 mmHg or an increase from baseline of = 15 mm Hg diastolic BP and dBP>100 mmHg. Increases from baseline in blood pressure must be confirmed by repeat measurement. - Time to an increase in blood pressure as defined in 3) above. - Mean change in mean arterial pressure (MAP) averaged over Weeks 8-12. - Time to achieve first Hb response as defined by the primary endpoint. - Health related quality of life (HRQoL) will be assessed using the SF-36, vitality and physical functioning subscales. Both within treatment effect and between treatment effect will be assessed for Weeks 12, 28, and 52.;Timepoint(s) of evaluation of this end point: After completion of study and closure of data base. | — |
Countries
Australia, Bulgaria, Estonia, Latvia, Lithuania, Poland, Romania, Russian Federation, United States
Contacts
Public ContactLona Poole, MD (medical monitor)
FibroGen, Inc.
Outcome results
None listed