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

• Sponsor: FibroGen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02652819
• Collaborator: (none)
• Enrollment: 154
• Locations: 30
• Arms: 2
• Duration (Months): 18.4
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia	Drug: FG-4592; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: Dec 1, 2015
• Actual Primary Completion Date: Jan 24, 2017
• Actual Study Completion Date: Jun 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FG-4592 Intervention is investigational treatment FG-4592	Drug: FG-4592
Placebo Comparator: Placebo Double blinded placebo control	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change in Hb from baseline to the average level [Weeks 7 to 9 inclusive.]

   Change in Hb from baseline to the average level

Secondary Outcome Measures

1. The proportion of subjects who achieve a confirmed Hb response [up to and including Week 9]

   The proportion of subjects who achieve a confirmed Hb response

2. Proportion of subjects with mean Hb ≥10.0 g/dL [Weeks 7 to 9]

   Proportion of subjects with mean Hb ≥10.0 g/dL

3. Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged [Weeks 7 to 9]

   Mean change from baseline in low-density lipoprotein (LDL) cholesterol averaged

4. Effect on iron metabolism [Week 9]

   Measurement of serum iron

5. 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]

   Survey (SF-36) Physical Functioning (PF) subscore measured in Week 9 in the Full Analysis Set (FAS) subjects with baseline PF subscore below 35

6. Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50. [Week 9]

   Mean change from baseline in SF-36 vitality subscore measured in Week 9 in FAS subjects with baseline vitality subscore below 50.

7. Mean change from baseline in mean arterial blood pressure [Weeks 7 to 9]

   Mean change from baseline in mean arterial blood pressure

8. Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron) [Up to Week 9]

   Proportion of subjects who received rescue therapy (composite of blood transfusion, ESA use, and IV iron)

9. Percent of subjects with treatment-emergent adverse events (TEAEs). [Week 1 up to Week 53]

   Percent of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)

10. Number of subjects with treatment-emergent adverse events (TEAEs). [Week 1 up to Week 53]

    Number of subjects with treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs)

11. Changes from baseline in vital signs [Week 1 up to Week 53]

    Measurement of vital signs

12. Changes from baseline in ECG findings [Week 1 up to Week 53]

    ECG recordings

13. Changes from baseline in clinical laboratory values [Week 1 up to Week 53]

    Clinical laboratory values

14. Proportion of subjects on rescue therapy [Week 1 up to Week 53]

    Proportion of subjects on rescue therapy

15. Time to rescue therapy from date of first dose [Week 1 up to Week 53]

    Time to rescue therapy from date of first dose

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

7. Uncontrolled hypertension in the opinion of the investigator (eg, that requires change in anti-hypertensive medication within 2 weeks prior to randomization).

8. Diagnosis or suspicion (eg, complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma as shown on screening renal ultrasound.

9. 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.

10. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (eg, systemic lupus erythematosis [SLE], rheumatoid arthritis, celiac disease).

11. Clinically significant gastrointestinal bleeding.

12. 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.

13. Any prior functioning organ transplant or a scheduled organ transplantation, or anephric.

14. Anticipated elective surgery that could lead to significant blood loss during the study period.

15. 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.

16. Serum albumin <2.5 g/dL.

17. Androgen, deferoxamine, deferiprone, or deferasirox therapy within 12 weeks prior to Day 1.

18. Life expectancy of <12 months.

19. Blood transfusion within 12 weeks prior to Day 1 or anticipated need for transfusion.

20. IV iron supplement during the Screening Period and /or unwilling to withhold IV iron.

21. Immune suppressive or systematic steroid treatment within 12 weeks prior to Day 1.

22. History of alcohol or drug abuse within the past 2 years and inability to avoid consumption of more than >3 alcoholic beverages per day.

23. Prior treatment with FG-4592 or any hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).

24. Use of an investigational medication or treatment, participation in an investigational interventional study, or carryover effect of an investigational treatment expected during the study.

25. Women who are pregnant or breastfeeding.

26. Women of childbearing potential and men with sexual partners of child bearing potential who are not using adequate contraception.

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

Sponsors and Collaborators

• FibroGen

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: FibroGen
• ClinicalTrials.gov Identifier: NCT02652819
• Other Study ID Numbers: FGCL-4592-808
• First Posted: Jan 12, 2016
• Last Update Posted: Aug 24, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by FibroGen: Chronic Kidney Disease
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia

Study Results

No Results Posted as of Aug 24, 2017