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

Primary Purpose

Anemia

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
FG-4592
Placebo
Sponsored by
FibroGen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia focused on measuring Chronic Kidney Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Second Hospital of Anhui Medical University
  • 301 Hospital
  • Peking Union Medical College Hospital
  • Peking University First Hospital
  • Pekingg University, People's Hospital
  • The First Affiliated hospital of Third Military Medical University (Southwest Hospital)
  • Lan Zhou University Second Hospital
  • Guangdong General Hospital
  • Nanfang Hospital, Southern Medical University
  • Shenzhen People's Hospital
  • The First Affiliated hospital of Guangxi Medical University
  • The People's Hospital of Guangxi Zhuang Autonomous Region
  • The Second Xiangya Hospital of Central South University
  • The First Hospital of Baotou Medical School of Inner Mongolia University of Science and Technology
  • Jiangsu Province Hospital
  • Nanjing General Hospital of Nanjing Military Command
  • Zhongda Hospital Southeast University
  • The First Affiliated Hospital of Nanchang University
  • The First Affiliated Hospital of Dalian Medical University
  • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shandong Provincial Hospital
  • Huashan Hospital of Fudan University
  • Rui Jin Hospital Shanghai Jiao Tong University School of Medication
  • Shanghai Changzheng Hospital
  • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medication
  • The Second Hospital of Shanxi Medical University
  • West China Hospital, Sichuan Universtiy
  • Tianjin Medical University General Hospital
  • The First Affiliated Hospital, Zhejiang University
  • Ningbo No.2 Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

FG-4592

Placebo

Arm Description

Intervention is investigational treatment FG-4592

Double blinded placebo control

Outcomes

Primary Outcome Measures

Change in Hb from baseline to the average level
Change in Hb from baseline to the average level

Secondary Outcome Measures

The proportion of subjects who achieve a confirmed Hb response
The proportion of subjects who achieve a confirmed Hb response
Proportion of subjects with mean Hb ≥10.0 g/dL
Proportion of subjects with mean Hb ≥10.0 g/dL
Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged
Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged
Effect on iron metabolism
Measurement of serum iron
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
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.
Mean change from baseline in mean arterial blood pressure
Mean change from baseline in mean arterial blood pressure
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)
Percent of subjects with treatment-emergent adverse events (TEAEs).
Percent of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)
Number of subjects with treatment-emergent adverse events (TEAEs).
Number of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)
Changes from baseline in vital signs
Measurement of vital signs
Changes from baseline in ECG findings
ECG recordings
Changes from baseline in clinical laboratory values
Clinical laboratory values
Proportion of subjects on rescue therapy
Proportion of subjects on rescue therapy
Time to rescue therapy from date of first dose
Time to rescue therapy from date of first dose

Full Information

First Posted
December 31, 2015
Last Updated
August 23, 2017
Sponsor
FibroGen
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1. Study Identification

Unique Protocol Identification Number
NCT02652819
Brief Title
FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease Not on Dialysis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
December 2015 (undefined)
Primary Completion Date
January 24, 2017 (Actual)
Study Completion Date
June 13, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FibroGen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia
Keywords
Chronic Kidney Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
154 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FG-4592
Arm Type
Experimental
Arm Description
Intervention is investigational treatment FG-4592
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Double blinded placebo control
Intervention Type
Drug
Intervention Name(s)
FG-4592
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in Hb from baseline to the average level
Description
Change in Hb from baseline to the average level
Time Frame
Weeks 7 to 9 inclusive.
Secondary Outcome Measure Information:
Title
The proportion of subjects who achieve a confirmed Hb response
Description
The proportion of subjects who achieve a confirmed Hb response
Time Frame
up to and including Week 9
Title
Proportion of subjects with mean Hb ≥10.0 g/dL
Description
Proportion of subjects with mean Hb ≥10.0 g/dL
Time Frame
Weeks 7 to 9
Title
Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged
Description
Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged
Time Frame
Weeks 7 to 9
Title
Effect on iron metabolism
Description
Measurement of serum iron
Time Frame
Week 9
Title
Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35
Description
Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35
Time Frame
Week 9
Title
Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50.
Description
Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50.
Time Frame
Week 9
Title
Mean change from baseline in mean arterial blood pressure
Description
Mean change from baseline in mean arterial blood pressure
Time Frame
Weeks 7 to 9
Title
Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron)
Description
Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron)
Time Frame
Up to Week 9
Title
Percent of subjects with treatment-emergent adverse events (TEAEs).
Description
Percent of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)
Time Frame
Week 1 up to Week 53
Title
Number of subjects with treatment-emergent adverse events (TEAEs).
Description
Number of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)
Time Frame
Week 1 up to Week 53
Title
Changes from baseline in vital signs
Description
Measurement of vital signs
Time Frame
Week 1 up to Week 53
Title
Changes from baseline in ECG findings
Description
ECG recordings
Time Frame
Week 1 up to Week 53
Title
Changes from baseline in clinical laboratory values
Description
Clinical laboratory values
Time Frame
Week 1 up to Week 53
Title
Proportion of subjects on rescue therapy
Description
Proportion of subjects on rescue therapy
Time Frame
Week 1 up to Week 53
Title
Time to rescue therapy from date of first dose
Description
Time to rescue therapy from date of first dose
Time Frame
Week 1 up to Week 53

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ages 18 to 75 years 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. 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. No use of an erythropoiesis-stimulating agent (ESA) for at least 5 weeks before randomization. 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. 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). Body weight: 40 to 100 kg inclusive. 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: Any clinically significant infection or evidence of an active underlying infection. 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 liver disease. New York Heart Association Class III or IV congestive heart failure. 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. Uncontrolled hypertension in the opinion of the investigator (eg, that requires change in anti-hypertensive medication within 2 weeks prior to randomization). Diagnosis or suspicion (eg, complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma as shown on screening renal ultrasound. 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. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (eg, systemic lupus erythematosis [SLE], rheumatoid arthritis, celiac disease). Clinically significant gastrointestinal bleeding. 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. Any prior functioning organ transplant or a scheduled organ transplantation, or anephric. Anticipated elective surgery that could lead to significant blood loss during the study period. 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. Serum albumin <2.5 g/dL. Androgen, deferoxamine, deferiprone, or deferasirox therapy within 12 weeks prior to Day 1. Life expectancy of <12 months. Blood transfusion within 12 weeks prior to Day 1 or anticipated need for transfusion. IV iron supplement during the Screening Period and /or unwilling to withhold IV iron. Immune suppressive or systematic steroid treatment within 12 weeks prior to Day 1. History of alcohol or drug abuse within the past 2 years and inability to avoid consumption of more than >3 alcoholic beverages per day. Prior treatment with FG-4592 or any hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). Use of an investigational medication or treatment, participation in an investigational interventional study, or carryover effect of an investigational treatment expected during the study. Women who are pregnant or breastfeeding. Women of childbearing potential and men with sexual partners of child bearing potential who are not using adequate contraception. 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.
Facility Information:
Facility Name
The Second Hospital of Anhui Medical University
City
Hefei
State/Province
Anhui
Country
China
Facility Name
301 Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Peking University First Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Pekingg University, People's Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
The First Affiliated hospital of Third Military Medical University (Southwest Hospital)
City
Chongqing
State/Province
Chongqing
Country
China
Facility Name
Lan Zhou University Second Hospital
City
Lanzhou
State/Province
Gansu
Country
China
Facility Name
Guangdong General Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Nanfang Hospital, Southern Medical University
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Shenzhen People's Hospital
City
Shenzhen
State/Province
Guangdong
Country
China
Facility Name
The First Affiliated hospital of Guangxi Medical University
City
Nanning
State/Province
Guangxi
Country
China
Facility Name
The People's Hospital of Guangxi Zhuang Autonomous Region
City
Nanning
State/Province
Guangxi
Country
China
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
Country
China
Facility Name
The First Hospital of Baotou Medical School of Inner Mongolia University of Science and Technology
City
Baotou
State/Province
Inner Mongolia
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
Nanjing General Hospital of Nanjing Military Command
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
Zhongda Hospital Southeast University
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
The First Affiliated Hospital of Nanchang University
City
Nanchang
State/Province
Jiangxi
Country
China
Facility Name
The First Affiliated Hospital of Dalian Medical University
City
Dalian
State/Province
Liaoning
Country
China
Facility Name
The First Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
State/Province
Shaanxi
Country
China
Facility Name
Shandong Provincial Hospital
City
Jinan
State/Province
Shandong
Country
China
Facility Name
Huashan Hospital of Fudan University
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Rui Jin Hospital Shanghai Jiao Tong University School of Medication
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medication
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
The Second Hospital of Shanxi Medical University
City
Taiyuan
State/Province
Shanxi
Country
China
Facility Name
West China Hospital, Sichuan Universtiy
City
Chengdu
State/Province
Sichuan
Country
China
Facility Name
Tianjin Medical University General Hospital
City
Tianjin
State/Province
Tianjin
Country
China
Facility Name
The First Affiliated Hospital, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
Facility Name
Ningbo No.2 Hospital
City
Ningbo
State/Province
Zhejiang
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
36005278
Citation
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.
Results Reference
derived
PubMed Identifier
31340089
Citation
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.
Results Reference
derived

Learn more about this trial

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

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