FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease Not on Dialysis

Study Overview
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Brief Summary
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This is a randomized, multicenter, double-blind, placebo-controlled study of the treatment of anemia in subjects with CKD not on dialysis, with treatment up to 52 weeks.

Detailed Description
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This is a randomized, multicenter, double-blind, placebo-controlled study of the treatment of anemia in subjects with CKD not on dialysis. Eligible subjects are randomized to FG-4592 or placebo at a ratio of 2:1. The primary endpoint is change in Hb from baseline to the average level during Weeks 7 to 9 inclusive.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety of FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease Not on Dialysis

Conditions
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Anemia

Intervention / Treatment
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* Drug: FG-4592
* Drug: Placebo


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. Diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4, or 5, not receiving dialysis; with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation. No use of an erythropoiesis-stimulating agent (ESA) for at least 5 weeks before randomization. Mean of the two most recent Hb values during the Screening Period obtained at least 6 days apart must be ≥7.0 g/dL and <10 g/dL. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 x upper limit of normal (ULN), and normal total bilirubin at screening visit (based on central laboratory results). Body weight: 40 to 100 kg inclusive. Subjects agreeing 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 without approval of the FibroGen China Medical Monitor. 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FG-4592<br>Intervention is investigational treatment FG-4592 | Drug: FG-4592<br> <br> |
| Placebo Comparator: Placebo<br>Double blinded placebo control | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hb from baseline to the average level | Change in Hb from baseline to the average level | Weeks 7 to 9 inclusive. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects who achieve a confirmed Hb response | The proportion of subjects who achieve a confirmed Hb response | up to and including Week 9 | 
| Proportion of subjects with mean Hb ≥10.0 g/dL | Proportion of subjects with mean Hb ≥10.0 g/dL | Weeks 7 to 9 | 
| Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged | Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged | Weeks 7 to 9 | 
| Effect on iron metabolism | Measurement of serum iron | Week 9 | 
| Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35 | Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35 | Week 9 | 
| Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50. | Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50. | Week 9 | 
| Mean change from baseline in mean arterial blood pressure | Mean change from baseline in mean arterial blood pressure | Weeks 7 to 9 | 
| Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron) | Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron) | Up to Week 9 | 
| Percent of subjects with treatment-emergent adverse events (TEAEs). | Percent of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) | Week 1 up to Week 53 | 
| Number of subjects with treatment-emergent adverse events (TEAEs). | Number of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) | Week 1 up to Week 53 | 
| Changes from baseline in vital signs | Measurement of vital signs | Week 1 up to Week 53 | 
| Changes from baseline in ECG findings | ECG recordings | Week 1 up to Week 53 | 
| Changes from baseline in clinical laboratory values | Clinical laboratory values | Week 1 up to Week 53 | 
| Proportion of subjects on rescue therapy | Proportion of subjects on rescue therapy | Week 1 up to Week 53 | 
| Time to rescue therapy from date of first dose | Time to rescue therapy from date of first dose | Week 1 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