FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease

Study Overview
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Brief Summary
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This is a randomized, multicenter, open-label, active-controlled study of the treatment of anemia in subjects with CKD on dialysis, with treatment up to 52 weeks.

Detailed Description
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This is a randomized, multicenter, open-label, active-controlled study of the treatment of anemia in subjects with CKD on dialysis. Eligible subjects are randomized to FG-4592 or epoetin alfa at a ratio of 2:1. The primary endpoint is Hb mean change from baseline averaged over Weeks 23 to 27.

Official Title
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A Phase 3, Randomized, Open-Label, Active-Controlled Study of Efficacy and Safety of FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease on Dialysis

Conditions
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Anemia

Intervention / Treatment
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* Drug: FG-4592
* Drug: Epoetin Alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18 to 75 years Subject has voluntarily signed and dated an informed consent form (ICF), approved by an Ethics Committee (EC), after the nature of the study has been explained and the subject has had the opportunity to ask questions; a separate ICF is needed for subjects participating in the PK Sub-study. Chronic kidney disease with end-stage renal disease (ESRD) on either adequate hemodialysis (HD) or adequate peritoneal dialysis for a minimum of 16 weeks prior to Day 1: For subjects undergoing HD, the vascular access must be via native arteriovenous (AV) fistula or graft, or permanent, tunneled catheter. Subjects must be on stable doses of IV or subcutaneous (SC) injections of epoetin alfa for at least 6 weeks prior to Day 1 (average dose ≤15,000 IU/week) Mean of the two most recent central laboratory Hb values during the Screening Period, obtained at least 6 days apart, must be 9.0 g/dL to 12.0 g/dL, inclusive, with a difference of \≤1.5 g/dL between the highest and the lowest Hb values. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 x upper limit of normal (ULN), and normal total bilirubin at screening visit except for subjects with Gilberts syndrome (based on central laboratory results). Body weight: 45 to 100 kg inclusive 8 Subjects agree not to start taking any new Traditional Chinese Medicine (TCM) for anemia and not to change dose, schedule, or brand of any prescreening TCM for anemia from beginning of Screening Period through end of Follow-up Period. Exclusion Criteria: Any clinically significant infection or evidence of an active underlying infection. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab). Chronic liver disease. New York Heart Association Class III or IV congestive heart failure. Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thromboembolic event (eg, deep venous thrombosis or pulmonary embolism) within 52 weeks prior to Day 1. Uncontrolled hypertension in the opinion of the investigator (eg, that requires change in anti-hypertensive medication within 2 weeks prior to randomization). Diagnosis or suspicion (eg, complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma as shown on screening renal ultrasound. History of malignancy except the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, or in situ cancer at any site. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (eg, systemic lupus erythematosis [SLE], rheumatoid arthritis, celiac disease). Clinically significant gastrointestinal bleeding. Known history of myelodysplastic syndrome, multiple myeloma, hereditary hematologic disease such as thalassemia, sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD, hemosiderosis, hemochromatosis, known coagulation disorder, or hypercoagulable condition. Any prior functioning organ transplant or a scheduled organ transplantation, or anephric. Anticipated elective surgery that could lead to significant blood loss during the study period. Anticipated use of dapsone or acetaminophen (paracetamol) >2.0 g/day, or >500 mg per dose repeated every 6 hours for more than 3 days. Serum albumin <2.5 g/dL. Androgen, deferoxamine, deferiprone, or deferasirox therapy within 12 weeks prior to Day 1. Life expectancy of <12 months. Blood transfusion within 12 weeks prior to Day 1 or anticipated need for transfusion. IV iron supplement during the Screening Period and /or unwilling to withhold IV iron. Immune suppressive or systematic steroid treatment within 12 weeks prior to Day 1. History of alcohol or drug abuse within the past 2 years and inability to avoid consumption of more than >3 alcoholic beverages per day. Prior treatment with FG-4592 or any hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). Use of an investigational medication or treatment, participation in an investigational interventional study, or carryover effect of an investigational treatment expected during the study. Women who are pregnant or breastfeeding. Women of childbearing potential and men with sexual partners of child bearing potential who are not using adequate contraception. Any medical condition that, in the opinion of the investigator, may pose a safety risk to a subject in this study, may confound efficacy or safety assessment, or may interfere with study participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FG-4592<br>Intervention is investigational treatment FG-4592 | Drug: FG-4592<br> <br> |
| Active Comparator: EPO<br>Intervention is subject's current dose of Li Xue Bao (epoetin alfa) | Drug: Epoetin Alfa<br> <br> * Other names: Li Xue Bao;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hb mean change from baseline | Hb mean change from baseline | Weeks 23 to 27. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in low-density lipoprotein (LDL) cholesterol | Mean change from baseline in low-density lipoprotein (LDL) cholesterol | Weeks 25-27 | 
| Number of subjects with a Hb response | Number of subjects with a Hb response (as defined per protocol) | Weeks 23-27 | 
| Percent of subjects with a Hb response | Percent of subjects with a Hb response (as defined per protocol) | Weeks 23-27 | 
| Effect on iron metabolism | Measurement of serum iron | Week 27 | 
| Proportion of subjects with exacerbation of hypertension | Proportion of subjects with exacerbation of hypertension, meeting at least one of the following criteria up to Week 27: Increase in anti-hypertensive medication use, Adverse event of hypertension, or Increases from baseline in blood pressure confirmed by repeat measurement at next visit unless anti-hypertensive medications are changed. | Up to Week 27 | 
| Mean change from baseline in predialysis and postdialysis mean arterial blood pressure | Mean arterial blood pressure measured pre-and post-dialysis. | Weeks 23-27 | 
| Number of subjects with treatment-emergent adverse events (TEAEs). | Number of subjects with treatment-emergent adverse events (TEAEs). | Week 1 to up to Week 53 | 
| Percent of subjects with treatment-emergent adverse events (TEAEs). | Percent of subjects with treatment-emergent adverse events (TEAEs). | Week 1 to up to Week 53 | 
| Changes from baseline in vital signs | Measurement of vital signs | Week 1 to up to Week 53 | 
| Changes from baseline in ECG findings. | ECG recordings. | Week 1 to up to Week 53 | 
| Changes from baseline in clinical laboratory values. | Clinical laboratory values. | Week 1 to up to Week 53 | 
| Number and % of subjects on rescue therapy during study treatment. | Number and % of subjects on rescue therapy during study treatment. | Week 1 to up to Week 53 | 
| Time to rescue therapy from date of first dose during study treatment. | Time to rescue therapy from date of first dose during study treatment. | Week 1 to up to Week 53 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease