Clinical trial NCT02652806 (phase 3, status: completed)
Conditions: anemia
ICD codes: D53.2, D64.9, D46.4, D53.0, D53.9, D61.3, D61.9
Drugs: fg-4592, epoetin alfa
SMILES: CC1=NC(C(=O)NCC(O)=O)=C(O)C2=CC=C(OC3=CC=CC=C3)C=C12, OC(=O)CNC(=O)C1C(=O)N(C2CCCCC2)C(=O)N(C2CCCCC2)C1=O
Eligibility criteria:

        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; a separate ICF is needed for
             subjects participating in the PK Sub-study.

          3. "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."

          4. 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)

          5. 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.

          6. 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).

          7. 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:

          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.