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

Sponsor

FibroGen (Industry)

Overall Status

Completed

CT.gov ID

NCT02652806

Collaborator

(none)

305

Enrollment

Locations

Arms

18.4

Duration (Months)

9.8

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Anemia	Drug: FG-4592 Drug: Epoetin Alfa	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

305 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Dec 1, 2015

Actual Primary Completion Date :

Jan 24, 2017

Actual Study Completion Date :

Jun 14, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Hb mean change from baseline [Weeks 23 to 27.]
Hb mean change from baseline

Secondary Outcome Measures

Mean change from baseline in low-density lipoprotein (LDL) cholesterol [Weeks 25-27]
Mean change from baseline in low-density lipoprotein (LDL) cholesterol
Number of subjects with a Hb response [Weeks 23-27]
Number of subjects with a Hb response (as defined per protocol)
Percent of subjects with a Hb response [Weeks 23-27]
Percent of subjects with a Hb response (as defined per protocol)
Effect on iron metabolism [Week 27]
Measurement of serum iron
Proportion of subjects with exacerbation of hypertension [Up to Week 27]
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.
Mean change from baseline in predialysis and postdialysis mean arterial blood pressure [Weeks 23-27]
Mean arterial blood pressure measured pre-and post-dialysis.
Number of subjects with treatment-emergent adverse events (TEAEs). [Week 1 to up to Week 53]
Number of subjects with treatment-emergent adverse events (TEAEs).
Percent of subjects with treatment-emergent adverse events (TEAEs). [Week 1 to up to Week 53]
Percent of subjects with treatment-emergent adverse events (TEAEs).
Changes from baseline in vital signs [Week 1 to up to Week 53]
Measurement of vital signs
Changes from baseline in ECG findings. [Week 1 to up to Week 53]
ECG recordings.
Changes from baseline in clinical laboratory values. [Week 1 to up to Week 53]
Clinical laboratory values.
Number and % of subjects on rescue therapy during study treatment. [Week 1 to up to Week 53]
Number and % of subjects on rescue therapy during study treatment.
Time to rescue therapy from date of first dose during study treatment. [Week 1 to up to Week 53]
Time to rescue therapy from date of first dose during study treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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; a separate ICF is needed for subjects participating in the PK Sub-study.
"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."
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)
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.
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).
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:

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
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Second Hospital of Anhui Medical University	Hefei	Anhui	China
2	301 Hospital	Beijing	Beijing	China
3	Peking Union Medical College Hospital	Beijing	Beijing	China
4	Peking University First Hospital	Beijing	Beijing	China
5	Peking University Third Hospital	Beijing	Beijing	China
6	Pekingg University, People's Hospital	Beijing	Beijing	China
7	The First Affiliated hospital of Third Military Medical University (Southwest Hospital)	Chongqing	Chongqing	China
8	Lan Zhou University Second Hospital	Lanzhou	Gansu	China
9	Guangdong General Hospital	Guangzhou	Guangdong	China
10	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong	China
11	Shenzhen People's Hospital	Shenzhen	Guangdong	China
12	The First Affiliated hospital of Guangxi Medical University	Nanning	Guangxi	China
13	The People's Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi	China
14	The Second Xiangya Hospital of Central South University	Changsha	Hunan	China
15	The First Hospital of Baotou Medical School of Inner Mongolia University of Science and Technology	Baotou	Inner Mongolia	China
16	Jiangsu Province Hospital	Nanjing	Jiangsu	China
17	Nanjing General Hospital of Nanjing Military Command	Nanjing	Jiangsu	China
18	Zhongda Hospital Southeast University	Nanjing	Jiangsu	China
19	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China
20	The First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning	China
21	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi	China
22	Shandong Provincial Hospital	Jinan	Shandong	China
23	Rui Jin Hospital Shanghai Jiao Tong University School of Medication	Shanghai	Shanghai	China	200025
24	Huashan Hospital of Fudan University	Shanghai	Shanghai	China	200040
25	Shanghai Changzheng Hospital	Shanghai	Shanghai	China
26	Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medication	Shanghai	Shanghai	China
27	The Second Hospital of Shanxi Medical University	Taiyuan	Shanxi	China
28	West China Hospital, Sichuan Universtiy	Chengdu	Sichuan	China
29	Tianjin Medical University General Hospital	Tianjin	Tianjin	China
30	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang	China
31	Ningbo No.2 Hospital	Ningbo	Zhejiang	China