Clinical trial NCT02652819: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Keywords: Chronic Kidney Disease
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
First posted: 2016-01-12
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Hb from baseline to the average level
timeFrame: Weeks 7 to 9 inclusive.
Secondary outcomes:
measure: The proportion of subjects who achieve a confirmed Hb response
timeFrame: up to and including Week 9
measure: Proportion of subjects with mean Hb ≥10.0 g/dL
timeFrame: Weeks 7 to 9
measure: Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged
timeFrame: Weeks 7 to 9
measure: Effect on iron metabolism
timeFrame: Week 9
measure: Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35
timeFrame: Week 9
measure: Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50.
timeFrame: Week 9
measure: Mean change from baseline in mean arterial blood pressure
timeFrame: Weeks 7 to 9
measure: Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron)
timeFrame: Up to Week 9
measure: Percent of subjects with treatment-emergent adverse events (TEAEs).
timeFrame: Week 1 up to Week 53
measure: Number of subjects with treatment-emergent adverse events (TEAEs).
timeFrame: Week 1 up to Week 53
measure: Changes from baseline in vital signs
timeFrame: Week 1 up to Week 53
measure: Changes from baseline in ECG findings
timeFrame: Week 1 up to Week 53
measure: Changes from baseline in clinical laboratory values
timeFrame: Week 1 up to Week 53
measure: Proportion of subjects on rescue therapy
timeFrame: Week 1 up to Week 53
measure: Time to rescue therapy from date of first dose
timeFrame: Week 1 up to Week 53
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: 301 Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Pekingg University, People's Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated hospital of Third Military Medical University (Southwest Hospital)
state: Chongqing
city: Lanzhou
country: China
facility: Lan Zhou University Second Hospital
state: Gansu
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated hospital of Guangxi Medical University
state: Guangxi
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Baotou
country: China
facility: The First Hospital of Baotou Medical School of Inner Mongolia University of Science and Technology
state: Inner Mongolia
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing General Hospital of Nanjing Military Command
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medication
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Shanghai
country: China
facility: Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medication
state: Shanghai
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan Universtiy
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo No.2 Hospital
state: Zhejiang
Study officials:
References:
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.
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.