FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease

A Phase 3, Randomized, Open-Label, Active-Controlled Study of Efficacy and Safety of FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease on Dialysis

This is a randomized, multicenter, open-label, active-controlled study of the treatment of anemia in subjects with CKD on dialysis, with treatment up to 52 weeks.

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Drug: FG-4592; Drug: Epoetin Alfa

Detailed Description

This is a randomized, multicenter, open-label, active-controlled study of the treatment of anemia in subjects with CKD on dialysis. Eligible subjects are randomized to FG-4592 or epoetin alfa at a ratio of 2:1. The primary endpoint is Hb mean change from baseline averaged over Weeks 23 to 27.

• Study Type: Interventional
• Enrollment (Actual): 305
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • The Second Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China
      • Peking University Third Hospital
    • Beijing, Beijing, China
      • 301 Hospital
    • Beijing, Beijing, China
      • Peking University first hospital
    • Beijing, Beijing, China
      • Pekingg University, People's Hospital
  • Chongqing
    • Chongqing, Chongqing, China
      • The First Affiliated hospital of Third Military Medical University (Southwest Hospital)
  • Gansu
    • Lanzhou, Gansu, China
      • Lan Zhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangdong General Hospital
    • Guangzhou, Guangdong, China
      • Nanfang Hospital, Southern Medical University
    • Shenzhen, Guangdong, China
      • ShenZhen People's Hospital
  • Guangxi
    • Nanning, Guangxi, China
      • The First Affiliated Hospital of Guangxi Medical University
    • Nanning, Guangxi, China
      • The People's Hospital of Guangxi Zhuang Autonomous Region
  • Hunan
    • Changsha, Hunan, China
      • The Second Xiangya Hospital Of Central South University
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • The First Hospital of Baotou Medical School of Inner Mongolia University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China
      • Nanjing General Hospital of Nanjing Military Command
    • Nanjing, Jiangsu, China
      • Zhongda Hospital Southeast University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital Of Nanchang University
  • Liaoning
    • Dalian, Liaoning, China
      • The First Affiliated Hospital of Dalian Medical University
  • Shaanxi
    • Xi'an, Shaanxi, China
      • The First Affiliated Hospital of Xi'An JiaoTong University
  • Shandong
    • Jinan, Shandong, China
      • Shandong Provincial Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medication
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital of Fudan University
    • Shanghai, Shanghai, China
      • Shanghai Changzheng Hospital
    • Shanghai, Shanghai, China
      • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medication
  • Shanxi
    • Taiyuan, Shanxi, China
      • The Second Hospital of Shanxi Medical University
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital, Sichuan Universtiy
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University
    • Ningbo, Zhejiang, China
      • Ningbo No.2 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. 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.

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; Intervention is investigational treatment FG-4592	Drug: FG-4592
Active Comparator: EPO; Intervention is subject's current dose of Li Xue Bao (epoetin alfa)	Drug: Epoetin Alfa; Other Names: Li Xue Bao

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hb mean change from baseline	Hb mean change from baseline	Weeks 23 to 27.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in low-density lipoprotein (LDL) cholesterol	Mean change from baseline in low-density lipoprotein (LDL) cholesterol	Weeks 25-27
Number of subjects with a Hb response	Number of subjects with a Hb response (as defined per protocol)	Weeks 23-27
Percent of subjects with a Hb response	Percent of subjects with a Hb response (as defined per protocol)	Weeks 23-27
Effect on iron metabolism	Measurement of serum iron	Week 27
Proportion of subjects with exacerbation of hypertension	Proportion of subjects with exacerbation of hypertension, meeting at least one of the following criteria up to Week 27: Increase in anti-hypertensive medication use,; Adverse event of hypertension, or; Increases from baseline in blood pressure confirmed by repeat measurement at next visit unless anti-hypertensive medications are changed.	Up to Week 27
Mean change from baseline in predialysis and postdialysis mean arterial blood pressure	Mean arterial blood pressure measured pre-and post-dialysis.	Weeks 23-27
Number of subjects with treatment-emergent adverse events (TEAEs).	Number of subjects with treatment-emergent adverse events (TEAEs).	Week 1 to up to Week 53
Percent of subjects with treatment-emergent adverse events (TEAEs).	Percent of subjects with treatment-emergent adverse events (TEAEs).	Week 1 to up to Week 53
Changes from baseline in vital signs	Measurement of vital signs	Week 1 to up to Week 53
Changes from baseline in ECG findings.	ECG recordings.	Week 1 to up to Week 53
Changes from baseline in clinical laboratory values.	Clinical laboratory values.	Week 1 to up to Week 53
Number and % of subjects on rescue therapy during study treatment.	Number and % of subjects on rescue therapy during study treatment.	Week 1 to up to Week 53
Time to rescue therapy from date of first dose during study treatment.	Time to rescue therapy from date of first dose during study treatment.	Week 1 to up to Week 53

Collaborators and Investigators

• Sponsor: FibroGen

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.
• Chen N, Hao C, Liu BC, Lin H, Wang C, Xing C, Liang X, Jiang G, Liu Z, Li X, Zuo L, Luo L, Wang J, Zhao MH, Liu Z, Cai GY, Hao L, Leong R, Wang C, Liu C, Neff T, Szczech L, Yu KP. Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis. N Engl J Med. 2019 Sep 12;381(11):1011-1022. doi: 10.1056/NEJMoa1901713. Epub 2019 Jul 24.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): January 24, 2017
• Study Completion (Actual): June 14, 2017

Study Registration Dates

• First Submitted: December 31, 2015
• First Submitted That Met QC Criteria: January 8, 2016
• First Posted (Estimate): January 12, 2016

Study Record Updates

• Last Update Posted (Actual): August 24, 2017
• Last Update Submitted That Met QC Criteria: August 23, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: FGCL-4592-806