Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of the Efficacy and Safety of FG-4592 in the Treatment of Anemia in Incident-Dialysis Patients
Brief Summary: The purpose of this study is to determine whether roxadustat is safe and effective in the treatment of anemia in participants who have just begun dialysis treatment for ESRD.


Options:
A: Inclusion Criteria:

* Participant has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines.
* Receiving HD or PD for ESRD for a minimum of 2 weeks and a maximum of 4 months, prior to randomization.
* Hemodialysis access consisting of an arteriovenous (AV) fistula, AV graft, or tunnelled (permanent) catheter; or PD catheter in use.
* Mean of the two most recent predialysis Hb values during the Screening Period, obtained at least 2 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.
* Ferritin ≥ 100 nanograms (ng)/milliliter (mL) (≥ 220 picomoles (pmol)/L); participants with ferritin level \< 100 ng/mL(\<220 pmol/L) during screening, qualify after receiving iron supplement (per local standard of care), without the need to retest ferritin prior to randomization.
* Transferrin saturation ≥ 20%; participants with TSAT level \< 20% during screening, qualify after receiving iron supplement (per local standard of care), without the need to retest TSAT prior to randomization.
* Serum folate level, performed within 8 weeks prior to randomization ≥ lower limit of normal (LLN); participants with serum folate level \< LLN during screening, qualify after receiving folate supplement (per local standard of care), without the need to retest folate prior to randomization.
* Serum vitamin B12 level, performed within 8 weeks prior to randomization ≥ LLN; participants with vitamin B12 level \< LLN during screening, qualify after receiving B12 supplement (per local standard of care), without the need to retest B12 prior to randomization.
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3 \* upper limit of normal (ULN), and total bilirubin ≤ 1.5 \* ULN.
* Body weight up to 160 kg (HD participants: dry weight).

Exclusion Criteria:

* Total duration of prior effective ESA use must be ≤3 weeks within the preceding 12 weeks at the time informed consent is obtained.

Specific dosing guidance, depending on the type of ESAs, injected IV or SC within 12 weeks prior to start of screening are as follows:

i) Short-acting ESAs (EPO-alfa or equivalents) - IV: Up to 9 doses, last EPO dose must be ≥2 days prior to start of screening; SC: Up to 3 doses, last EPO dose must be ≥1 week (7 days) prior to start of screening ii) Darbepoetin - IV: Up to 3 doses, last darbepoetin dose must be ≥1 week (7 days) prior to start of screening; SC: Up to 2 doses, last darbepoetin dose must be ≥2 weeks (14 days) prior to start of screening iii) Continuous erythropoietin receptor activator (CERA) IV and SC: Up to 2 doses; last CERA dose must be ≥2 weeks (14 days) prior to start of screening

* Intravenous iron: there is no restriction regarding IV iron use during screening, provided it is administered in accordance with local SOC.
* Red blood cell transfusion within 4 weeks prior to randomization.
* 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 at the time of randomization.
* History of chronic liver disease (for example, chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis, or fibrosis of the liver).
* New York Heart Association Class III or IV congestive heart failure at screening.
* Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thromboembolic event within a major vessel (excluding vascular dialysis access) (for example, deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
* Uncontrolled hypertension, in the opinion of the Investigator, (for example, that requires a change in anti-hypertensive medication) within 2 weeks prior to randomization.
* Renal imaging performed within 12 weeks prior to randomization indicative of a diagnosis or suspicion (for example, complex kidney cyst of Bosniak Category 2 or higher) of renal cell carcinoma.
* 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.
* 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 inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
* Known, untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration, or retinal vein occlusion (participants who are already blind for the above reasons qualify to participate).
* Known history of myelodysplastic syndrome or multiple myeloma.
* 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).
* Known hemosiderosis, hemochromatosis, coagulation disorder, or a hypercoagulable condition.
* Organ transplant: participants with any of the following:

  1. Experienced rejection of a transplanted organ within 6 months of transplantation
  2. Currently on high doses of immunosuppressive therapy (per discretion of the Investigator)
  3. Scheduled for organ transplantation. Note: being on a waiting list for kidney transplant is not exclusionary
* 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.
* Active or chronic gastrointestinal bleeding.
* Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).
* Use of iron-chelating agents within 4 weeks prior to randomization.
* Known hypersensitivity reaction to any ESA.
* 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.
* Anticipated use of dapsone or androgens at any dose amount or chronic use of acetaminophen or paracetamol \> 2.0 g/day during the study.
* History of alcohol or drug abuse within 6 months prior to randomization.
* Females of childbearing potential, unless using contraception as detailed in the protocol; male participants with sexual partners of childbearing potential who are not on birth control unless the male participant agrees to use contraception.
* Pregnant or breastfeeding females.
* Any medical condition that, in the opinion of the Investigator, may pose a safety risk to a participant in this study, may confound efficacy or safety assessment, or may interfere with study participation.
B: Inclusion Criteria:

* Subject with end-stage kidney disease (ESKD) on peritoneal dialysis prior to assignment and not expected to start maintenance dialysis (e.g., hemodialysis, hemodiafiltration) other than peritoneal dialysis during the study period
* Body weight \> 40 and ≤ 160 kg at screening
* Male or female subject ≥ 20 years of age at screening
* At least one kidney
* Subjects who meet one of the 1 or 2 following criteria

  * Subjects untreated with ESA at assignment: Mean of the last 2 Hb level (central laboratory measurement) during the screening period must be ≥ 8.0 and \< 11.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be \< 1.2 g/dL) with the last screening Hb measurement within 14 days prior to study drug assignment
  * Subjects pre treated with ESA at assignment: Mean of the last 2 Hb level (central laboratory measurement) during the screening period must be ≥ 10.0 and \< 13.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be \< 1.2 g/dL) with the last screening Hb measurement within 14 days prior to study drug assignment
* Subjects who meet one of the 1 or 2 following criteria

  * Subjects untreated with ESA at assignment: Subject with ESKD on peritoneal dialysis for at least 2 weeks prior to assignment. AND. Subject not received ESA for 8 weeks prior to assignment. OR. In case of the patient washed out from ESAs, when mean of the last 2 Hb level (at least 2 central laboratory measurements must be taken ≥ 2 days apart) has decrease to ≥ 0.5g/dL from the Hb level (central laboratory measurement) after the last ESA administration, AND the interval from the last ESA administration to the study drug assignment should be over 2 week for epoetin-alpha/beta, 4 weeks for darbepoetin alpha or epoetin beta pegol
  * Subjects pre treated with ESA at assignment:

    * Subject with ESKD on peritoneal dialysis for at least 12 weeks prior to assignment
    * Subject treated with ESA by IV or SC within 8 weeks prior to assignment
    * Treated with 2 or 4 weekly dose of darbepoetin alfa, 4 weekly dose of epoetin beta pegol, OR 3 times per week, twice per week, weekly or bi-weekly dose of epoetin alfa/beta, and having had no more than one dose change within 8 weeks prior to assignment

Exclusion Criteria:

* New York Heart Association (NYHA) Class III or IV congestive heart failure
* History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, pulmonary thromboembolism, and acute limb ischemia) within 6 months prior to randomization
* Sustained and poorly controlled arterial hypertension (defined as systolic BP≥ 180mmHg or diastolic BP ≥ 110mmHg) or hypotension (defined as systolic BP \< 90mmHg) at randomization
* Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy requiring invasive treatment (e.g., intraocular injections or laser photocoagulation)
C: Inclusion Criteria:

* Receiving HD or PD for native kidney end-stage renal disease (ESRD) for 2 weeks to 4 months, prior to randomization
* Mean of the 2 most recent Hb values during the screening period, obtained at least 7 days apart, must be \<10.0 grams (g)/deciliter (dL), with a difference of ≤1.0 g/dL between the 2 values
* Body weight 40 to 140 kilograms (kg)

Exclusion Criteria:

* Previously received erythropoiesis-stimulating agents
* Received IV iron within 4 weeks of randomization
* Received red blood cell transfusion within 8 weeks prior to randomization or anticipated need for transfusion during the treatment period
* Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab)
* History of chronic liver disease
* Clinically significant infection
* New York Heart Association Class III or IV congestive heart failure
* 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, cervical cancer in situ, or resected colonic polyps
* Chronic inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
* History of other blood disorders
* Active hemolysis or diagnosis of hemolytic syndrome
* Known bone marrow fibrosis
* Uncontrolled or symptomatic secondary hyperparathyroidism
* History of alcohol or drug abuse within a year prior to randomization, or anticipated inability to avoid consumption of more than 3 alcoholic beverages per day
* History of allergy or sensitivity to oral or IV iron therapy
* Seizure disorder or receiving anti-epilepsy medication for seizure disorder within 12 weeks prior to randomization
* Pregnant or breast-feeding females
D: Inclusion Criteria:

1. The patient or his/her legal guardian signs the informed consent
2. Age ≥18 years
3. Weight: 45-100 kg (included)
4. Patients with CKD end-stage renal disease received hemodialysis treatment ≤ 4 weeks, dialysis frequency was stable, kt / V ≥ 1.2, and planned to continue dialysis treatment during the study period
5. No iron deficiency.
6. No folate or Vitamin B12 deficiency.
7. No abnormal liver tests.
8. During the screening period, value of Hb is less than 10. 0 g / dl.

Exclusion Criteria:

1. Evidence of any clinically significant infection or active potential infection;
2. Active hepatitis or any of the following abnormalities (ALT ≥ 2 times the upper limit of normal value, AST ≥ 2 times the upper limit of normal value, DBIL ≥ 2 times the upper limit of normal value);
3. Patients with severe cardiovascular disease have had myocardial infarction, coronary artery bypass or PCI operation within 3 months prior to participating in the study.
4. Patients have experienced severe cerebrovascular diseases within 3 months prior to participating in the study: stroke; obvious neurological dysfunction after stroke;
5. Patients with active gastrointestinal bleeding occurred within 3 months prior to participating in the study.
6. Poor control of hypertension determined by the researchers;
7. Previous or current malignancies (except for excised non melanoma skin cancer and carcinoma in situ);
8. It is known to have blood system diseases (including congenital and postnatal diseases, such as thalassemia, Fanconi anemia, aplastic anemia, myelodysplastic syndrome, hemolytic anemia, coagulation dysfunction, etc.) or other causes of anemia (such as fecal occult blood positive gastrointestinal hemorrhage or hookworm disease, etc.) ;
9. Known autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, anti neutrophil cytoplasmic antibody associated vasculitis, etc.);
10. Any previous functional organ transplant or scheduled organ transplant or no kidney.
11. Elective surgery that is expected to result in significant blood loss during the study period.
12. Serum albumin \< 25 g / L;
13. Within 8 weeks before administration on the first day, the patients were treated with androgen, deferoxamine, deferrone or deferestrol.
14. Life expectancy \< 12 months;
15. Transfusion within 4 weeks before administration on day 1, or is expected.
16. Intravenous iron supplementation and / or unwillingness to stop intravenous iron injection during the screening period;
17. Patients with drug abuse or addiction;
18. Have received any test drug within 4 weeks before inclusion or plan to receive other drug tests during the trial;
19. Women who can become pregnant must use contraception. Men with sexual partners who can become pregnant must use birth control, unless the man agrees to use contraception.
20. Any medical condition, that in the opinion of the study doctor, may pose a safety risk to the patient, may confound efficacy or safety assessment, or may interfere with study participation.

Answer: A