Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis in China

A Phase 2, Randomized, Open-Label Active-Comparator (Epoetin Alfa) Dose-Ranging Safety and Exploratory Efficacy Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis (HD)

The purpose of this study is to evaluate the efficacy and safety of FG-4592 in maintaining and/or correcting hemoglobin (Hb) given to subjects with End Stage Renal Disease (ESRD) on maintenance hemodialysis and receiving epoetin alfa.

Study Overview

• Status: Completed
• Conditions: Anemia in End Stage Renal Disease
• Intervention / Treatment: Drug: FG-4592; Drug: Epoetin Alfa

Detailed Description

Dose ranging study with three consecutive dose escalation cohorts. The study objectives are to demonstrate that FG-4592 is effective in maintaining hemoglobin (Hb) levels when converting from epoetin alfa and to establish optimum starting doses and dose adjustment regimens for Hb maintenance.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University First Hospital
  • Beijing, China
    • Peking Union Medical College Hospital
  • Guangzhou, China
    • First Affiliated Hospital, Sun Yat-Sen University
  • Hangzhou, China
    • Zhejiang University No 1. Hospital
  • Shanghai, China
    • Ruijin Hospital
  • Shanghai, China
    • Renji Hospital
  • Shanghai, China
    • Xinhua Hospital
  • Shanghai, China
    • Chang Zheng Hospital
  • Shenzhen, China
    • Shenzhen people's hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has voluntarily signed and dated an informed consent form
2. Age 18 to 75 years
3. End-stage renal disease (ESRD) and receiving maintenance hemodialysis TIW for ≥4 months prior to Day 1
4. Hemoglobin (Hb) values in 4 screening visits and the mean Hb must be between 9.0 and 12.0 g/dL (inclusive), and the difference between them must be ≤1.5 g/dL.

5. Stable doses of IV or Subcutaneous injection of epoetin alfa, defined as follows:

   • Epoetin alfa dose range for 6 weeks prior to Day -7:

     3000 to 20,000 IU/week

   • Stable doses of epoetin alfa (i.e., the maximum epoetin alfa dose does not exceed 130% of the lowest dose of epoetin alfa taken in this period)
6. Complete Blood Count (CBC), Hematology, liver function blood tests within acceptable limits
7. Serum folate and vitamin B12 levels above the lower limit of normal (LLN)
8. Body weight: 40 to 100 kg (dry weight) inclusive
9. Body mass index (BMI): 16 to 38 kg/m2 inclusive
10. HD subjects: dialysis vascular access via native arteriovenous fistula or synthetic graft (not via catheter)

Exclusion Criteria:

1. Anticipated change in hemodialysis prescription or access during the screening or dosing period of the study
2. Any clinically significant infection or evidence of an underlying infection such as a white blood cell count (WBC) > ULN during screening on two separate occasions,
3. Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); anti-hepatitis C virus antibody (anti-HCV Ab)
4. History of chronic liver disease
5. New York Heart Association Class III or IV congestive heart failure
6. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
7. Active or chronic gastrointestinal bleeding, or a known coagulation disorder
8. Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.)
9. Hematological disorders, including myelodysplastic syndrome, multiple myeloma, or pure red cell aplasia
10. History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric
11. Active hemolysis or diagnosis of hemolytic syndrome
12. Known bone marrow fibrosis
13. Uncontrolled or symptomatic secondary hyperparathyroidism (PTH>600ng/L)
14. Any prior organ transplantation
15. Drug-treated gastroparesis, short-bowel syndrome, or any other gastrointestinal condition that may lead to reduced absorption of study drug
16. History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the subject
17. Prior treatment with FG-4592
18. Use of traditional Chinese medicines (TCM) during the screening visit to Day 1 or plans to use TCM during the study unless approved in advance by the Medical Monitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FG-4592; Active Drug	Drug: FG-4592; TIW dosing, capsule
Active Comparator: Epoetin alfa; Standard of care	Drug: Epoetin Alfa; TIW

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hemoglobin maintenance using FG-4592 dosing regimen in ESRD subjects. Number of subjects who hemoglobin levels are maintained at no lower than 0.5 g/dL below their mean baseline value during weeks 6 and 7.	Week 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Number (%) of subjects whose hemoglobin levels are between 9.0 and 13.0 g/dL at Weeks 3, 4, 5, 6 and 7.	Week 7
Number (%) of subjects whose hemoglobin levels at Weeks 3, 4, 5, 6 and 7 are greater than or equal to their baseline level.	Week 7

Collaborators and Investigators

• Sponsor: FibroGen
• Collaborators: Peking University First Hospital; Peking Union Medical College Hospital; First Affiliated Hospital, Sun Yat-Sen University; RenJi Hospital; Ruijin Hospital; First Affiliated Hospital of Zhejiang University; Shenzhen People's Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Chang Zheng Hospital

Publications and helpful links

General Publications

• Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: April 30, 2012
• First Submitted That Met QC Criteria: May 9, 2012
• First Posted (Estimate): May 11, 2012

Study Record Updates

• Last Update Posted (Estimate): February 4, 2013
• Last Update Submitted That Met QC Criteria: January 31, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Anemia; Renal
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Hematinics; Epoetin Alfa
• Other Study ID Numbers: FGCL-4592-048