Anemia
Conditions
Keywords
Chronic Kidney Disease
Brief summary
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
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.
Interventions
DRUGFG-4592
DRUGPlacebo
Sponsors
Kyntra Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 18 to 75 years 2. 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. 3. 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. 4. No use of an erythropoiesis-stimulating agent (ESA) for at least 5 weeks before randomization. 5. 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. 6. 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). 7. Body weight: 40 to 100 kg inclusive. 8. 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
1. Any clinically significant infection or evidence of an active underlying infection. 2. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab). 3. Chronic liver disease. 4. New York Heart Association Class III or IV congestive heart failure. 5. 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. 6. Uncontrolled hypertension in the opinion of the investigator (eg, that requires change in anti-hypertensive medication within 2 weeks prior to randomization). 7. Diagnosis or suspicion (eg, complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma as shown on screening renal ultrasound. 8. 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. 9. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (eg, systemic lupus erythematosis \[SLE\], rheumatoid arthritis, celiac disease). 10. Clinically significant gastrointestinal bleeding. 11. 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. 12. Any prior functioning organ transplant or a scheduled organ transplantation, or anephric. 13. Anticipated elective surgery that could lead to significant blood loss during the study period. 14. 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. 15. Serum albumin \<2.5 g/dL. 16. Androgen, deferoxamine, deferiprone, or deferasirox therapy within 12 weeks prior to Day 1. 17. Life expectancy of \<12 months. 18. Blood transfusion within 12 weeks prior to Day 1 or anticipated need for transfusion. 19. IV iron supplement during the Screening Period and /or unwilling to withhold IV iron. 20. Immune suppressive or systematic steroid treatment within 12 weeks prior to Day 1. 21. History of alcohol or drug abuse within the past 2 years and inability to avoid consumption of more than \>3 alcoholic beverages per day. 22. Prior treatment with FG-4592 or any hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). 23. Use of an investigational medication or treatment, participation in an investigational interventional study, or carryover effect of an investigational treatment expected during the study. 24. Women who are pregnant or breastfeeding. 25. Women of childbearing potential and men with sexual partners of child bearing potential who are not using adequate contraception. 26. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hb from baseline to the average level | Weeks 7 to 9 inclusive. | Change in Hb from baseline to the average level |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with mean Hb ≥10.0 g/dL | Weeks 7 to 9 | Proportion of subjects with mean Hb ≥10.0 g/dL |
| Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged | Weeks 7 to 9 | Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged |
| Effect on iron metabolism | Week 9 | Measurement of serum iron |
| 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 | Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35 |
| 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 SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50. |
| Mean change from baseline in mean arterial blood pressure | Weeks 7 to 9 | Mean change from baseline in mean arterial blood pressure |
| Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron) | Up to Week 9 | Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron) |
| The proportion of subjects who achieve a confirmed Hb response | up to and including Week 9 | The proportion of subjects who achieve a confirmed Hb response |
| Number of subjects with treatment-emergent adverse events (TEAEs). | Week 1 up to Week 53 | Number of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) |
| Changes from baseline in vital signs | Week 1 up to Week 53 | Measurement of vital signs |
| Changes from baseline in ECG findings | Week 1 up to Week 53 | ECG recordings |
| Changes from baseline in clinical laboratory values | Week 1 up to Week 53 | Clinical laboratory values |
| Proportion of subjects on rescue therapy | Week 1 up to Week 53 | Proportion of subjects on rescue therapy |
| Time to rescue therapy from date of first dose | Week 1 up to Week 53 | Time to rescue therapy from date of first dose |
| Percent of subjects with treatment-emergent adverse events (TEAEs). | Week 1 up to Week 53 | Percent of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) |
Countries
China
Outcome results
None listed