FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease Not on Dialysis

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety of FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease Not on Dialysis

This is a randomized, multicenter, double-blind, placebo-controlled study of the treatment of anemia in subjects with CKD not on dialysis, with treatment up to 52 weeks.

Study Overview

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

Detailed Description

This is a randomized, multicenter, double-blind, placebo-controlled study of the treatment of anemia in subjects with CKD not on dialysis.

Eligible subjects are randomized to FG-4592 or placebo at a ratio of 2:1. The primary endpoint is change in Hb from baseline to the average level during Weeks 7 to 9 inclusive.

• Study Type: Interventional
• Enrollment (Actual): 154
• 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
      • 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
      • Shanghai Changzheng Hospital
    • Shanghai, Shanghai, China
      • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medication
    • Shanghai, Shanghai, China
      • Huashan Hospital of Fudan University
    • Shanghai, Shanghai, China
      • Rui Jin Hospital 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.
3. Diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4, or 5, not receiving dialysis; with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation.
4. No use of an erythropoiesis-stimulating agent (ESA) for at least 5 weeks before randomization.
5. Mean of the two most recent Hb values during the Screening Period obtained at least 6 days apart must be ≥7.0 g/dL and <10 g/dL.
6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 x upper limit of normal (ULN), and normal total bilirubin at screening visit (based on central laboratory results).
7. Body weight: 40 to 100 kg inclusive.
8. Subjects agreeing 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 without approval of the FibroGen China Medical Monitor.

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: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FG-4592; Intervention is investigational treatment FG-4592	Drug: FG-4592
Placebo Comparator: Placebo; Double blinded placebo control	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hb from baseline to the average level	Change in Hb from baseline to the average level	Weeks 7 to 9 inclusive.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects who achieve a confirmed Hb response	The proportion of subjects who achieve a confirmed Hb response	up to and including Week 9
Proportion of subjects with mean Hb ≥10.0 g/dL	Proportion of subjects with mean Hb ≥10.0 g/dL	Weeks 7 to 9
Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged	Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged	Weeks 7 to 9
Effect on iron metabolism	Measurement of serum iron	Week 9
Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35	Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35	Week 9
Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50.	Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50.	Week 9
Mean change from baseline in mean arterial blood pressure	Mean change from baseline in mean arterial blood pressure	Weeks 7 to 9
Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron)	Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron)	Up to Week 9
Percent of subjects with treatment-emergent adverse events (TEAEs).	Percent of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)	Week 1 up to Week 53
Number of subjects with treatment-emergent adverse events (TEAEs).	Number of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)	Week 1 up to Week 53
Changes from baseline in vital signs	Measurement of vital signs	Week 1 up to Week 53
Changes from baseline in ECG findings	ECG recordings	Week 1 up to Week 53
Changes from baseline in clinical laboratory values	Clinical laboratory values	Week 1 up to Week 53
Proportion of subjects on rescue therapy	Proportion of subjects on rescue therapy	Week 1 up to Week 53
Time to rescue therapy from date of first dose	Time to rescue therapy from date of first dose	Week 1 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, Peng X, Lin H, Yin A, Hao L, Tao Y, Liang X, Liu Z, Xing C, Chen J, Luo L, Zuo L, Liao Y, Liu BC, Leong R, Wang C, Liu C, Neff T, Szczech L, Yu KP. Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis. N Engl J Med. 2019 Sep 12;381(11):1001-1010. doi: 10.1056/NEJMoa1813599. 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 13, 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: August 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
• Other Study ID Numbers: FGCL-4592-808