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.

Phase 1

• Conditions: Anemia due to end-stage renal disease in incident-dialysis patients.; MedDRA version: 20.0Level: LLTClassification code 10054606Term: Secondary anemiaSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-002753-30-LV
• Lead Sponsor: FibroGen, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-16
• Last Update Posted: 20 August 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

1. Age = 18 years.
2. Subject has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines.
3. Receiving HD or PD for ESRD for a minimum of 2 weeks and a maximum of 4 months, prior to randomization.
4. Hemodialysis access consisting of an arteriovenous (AV) fistula, AV graft, or tunnelled (permanent) catheter; or PD catheter in use.
5. 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.
6. Ferritin = 100 ng/mL (= 220 pmol/L); subjects with ferritin level < 100
ng/mL(<220pmol/L) during screening, qualify after receiving iron supplement (per local standard of care), without the need to retest ferritin prior to randomization.
7. Transferrin saturation = 20%; subjects 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.
8. Serum folate level, performed within 8 weeks prior to randomization = lower limit of normal (LLN); subjects 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.
9. Serum vitamin B12 level, performed within 8 weeks prior to randomization = LLN; subjects 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.
10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 3 x upper limit of normal (ULN), and total bilirubin (Tbili) = 1.5 x ULN.
11. Body weight up to 160 kg (HD subjects: dry weight).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1200

Exclusion Criteria

1. 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: 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
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
Continuous erythropoietin receptor activator (CERA) IV and SC
• IV or SC: Up to 2 doses; last CERA dose must be =2 weeks (14 days) prior to start of screening
2. Intravenous iron: there is no restriction regarding IV iron use during screening, provided it is administered in accordance with local standard of care.
3. Red blood cell transfusion within 4 weeks prior to randomization.
4. 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.
5. History of chronic liver disease (eg, chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis, or fibrosis of the liver).
6. New York Heart Association Class III or IV congestive heart failure at screening.
7. Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thromboembolic event within a major vessel (excluding vascular dialysis access) (eg, deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
8. Uncontrolled hypertension, in the opinion of the Investigator, (eg, that requires a change in anti-hypertensive medication) within 2 weeks prior to randomization.
9. Renal imaging performed within 12 weeks prior to randomization indicative of a diagnosis or suspicion (eg, complex kidney cyst of Bosniak Category 2 or higher) of renal cell carcinoma.
10. 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.
11. Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab).
12. Chronic inflammatory disease that could impact erythropoiesis (eg, systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
13. Known, untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration, or retinal vein occlusion (subjects who are already blind for the above reasons qualify to participate).
14. Known history of myelodysplastic syndrome or multiple myeloma.
15. Known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD.
16. Known hemosiderosis, hemochromatosis, coagulation disorder, or a hypercoagulable condition.
17. Organ transplant: subjects with any of the following:
a. Experienced rejection of a transplanted organ within 6 months of transplantation
b. Currently on high doses of immunosuppressive therapy (per discretion of the Investigator)
c. Scheduled for organ transplantation. Note: being on a wait

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified