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

Anemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02652819
• Other study ID #: FGCL-4592-808
• Status: Completed
• Phase: Phase 3
• First received: December 31, 2015
• Last updated: August 23, 2017
• Start date: December 2015
• Est. completion date: June 13, 2017

Study information

• Verified date: August 2017
• Source: FibroGen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: June 13, 2017
• Est. primary completion date: January 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• FG-4592

• Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
FibroGen

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hb from baseline to the average level	Change in Hb from baseline to the average level	Weeks 7 to 9 inclusive.
Secondary	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
Secondary	Proportion of subjects with mean Hb =10.0 g/dL	Proportion of subjects with mean Hb =10.0 g/dL	Weeks 7 to 9
Secondary	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
Secondary	Effect on iron metabolism	Measurement of serum iron	Week 9
Secondary	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
Secondary	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
Secondary	Mean change from baseline in mean arterial blood pressure	Mean change from baseline in mean arterial blood pressure	Weeks 7 to 9
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes from baseline in vital signs	Measurement of vital signs	Week 1 up to Week 53
Secondary	Changes from baseline in ECG findings	ECG recordings	Week 1 up to Week 53
Secondary	Changes from baseline in clinical laboratory values	Clinical laboratory values	Week 1 up to Week 53
Secondary	Proportion of subjects on rescue therapy	Proportion of subjects on rescue therapy	Week 1 up to Week 53
Secondary	Time to rescue therapy from date of first dose	Time to rescue therapy from date of first dose	Week 1 up to Week 53