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

Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02652806
• Other study ID #: FGCL-4592-806
• Status: Completed
• Phase: Phase 3
• First received: December 31, 2015
• Last updated: August 23, 2017
• Start date: December 2015
• Est. completion date: June 14, 2017

Study information

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

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: June 14, 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; 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.

Related Conditions & MeSH terms

• Anemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• FG-4592

• Epoetin Alfa

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	Peking University Third 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	Hb mean change from baseline	Hb mean change from baseline	Weeks 23 to 27.
Secondary	Mean change from baseline in low-density lipoprotein (LDL) cholesterol	Mean change from baseline in low-density lipoprotein (LDL) cholesterol	Weeks 25-27
Secondary	Number of subjects with a Hb response	Number of subjects with a Hb response (as defined per protocol)	Weeks 23-27
Secondary	Percent of subjects with a Hb response	Percent of subjects with a Hb response (as defined per protocol)	Weeks 23-27
Secondary	Effect on iron metabolism	Measurement of serum iron	Week 27
Secondary	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
Secondary	Mean change from baseline in predialysis and postdialysis mean arterial blood pressure	Mean arterial blood pressure measured pre-and post-dialysis.	Weeks 23-27
Secondary	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
Secondary	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
Secondary	Changes from baseline in vital signs	Measurement of vital signs	Week 1 to up to Week 53
Secondary	Changes from baseline in ECG findings.	ECG recordings.	Week 1 to up to Week 53
Secondary	Changes from baseline in clinical laboratory values.	Clinical laboratory values.	Week 1 to up to Week 53
Secondary	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
Secondary	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