Study of FG-4592 in Subjects With Chronic Kidney Disease in China

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Sequential Group, Dose Ranging Safety and Efficacy Study of FG 4592 in Non-dialysis Chronic Kidney Disease (CKD) Subjects With Anemia

The primary purpose of this study is to evaluate efficacy and safety of FG-4592 in the correction of anemia in non-dialysis chronic kidney disease patients.

Study Overview

• Status: Completed
• Conditions: Anemia in Chronic Kidney Disease
• Intervention / Treatment: Drug: FG-4592; Drug: Placebo

Detailed Description

Dose ranging study with two consecutive dose escalation cohorts. The study objective is to demonstrate that FG-4592 is effective in the correction of anemia in chronic kidney disease patients.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University first hospital
  • Beijing, China
    • Peking Union Medical College Hospital
  • Chengdu, China
    • Sichuan Provincial People's Hospital
  • Chengdu, China
    • West China Hospital
  • DaLian, China
    • First Affiliated Hospital of Dalian Medical University
  • Guangzhou, China
    • First Affiliated Hospital, Sun Yat-Sen University
  • Hangzhou, China
    • Zhejiang University No 1. Hospital
  • Shanghai, China
    • Ruijin Hospital
  • Shanghai, China
    • RenJi Hospital
  • Shanghai, China
    • Huashan Hospital
  • Shanghai, China
    • Xinhua Hospital
  • Shanghai, China
    • Chang Zheng Hospital
  • Shenzhen, China
    • ShenZhen People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 to 75 years
2. Subject has voluntarily signed and dated an informed consent form
3. Chronic Kidney Disease, not receiving dialysis
4. Hemoglobin (Hb) values in 4 screening visits and the mean Hb must be <10g/dL
5. Aminotransferase levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) and total bilirubin must be ≤ upper limit of normal (ULN) during the screening period
6. Serum alkaline phosphatase (ALP) ≤2x ULN during screening period. Subjects with serum ALP values between 1 x and 2 x ULN may be included only if bone-specific ALP (BSAP) is also elevated > ULN
7. Total bilirubin values must be ≤ULN during screening period
8. Serum folate and vitamin B12 levels above the lower limit of normal (LLN)
9. Body weight: 40 to 100 kg (dry weight) inclusive
10. Body mass index (BMI): 16 to 38 kg/m2 inclusive

Exclusion Criteria:

1. Received any erythropoiesis-stimulating agent (ESA) other than epoetin alfa within 12 weeks prior to Day 1
2. Any clinically significant infection or evidence of an underlying infection such as a white blood cell count (WBC) > ULN during screening on two separate occasions,
3. Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); anti-hepatitis C virus antibody (anti-HCV Ab)
4. History of chronic liver disease
5. New York Heart Association Class III or IV congestive heart failure
6. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
7. Active or chronic gastrointestinal bleeding, or a known coagulation disorder
8. Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.)
9. Hematological disorders, including myelodysplastic syndrome, multiple myeloma, or pure red cell aplasia
10. History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric
11. Active hemolysis or diagnosis of hemolytic syndrome
12. Known bone marrow fibrosis
13. Uncontrolled or symptomatic secondary hyperparathyroidism (PTH>600ng/L)
14. Any prior organ transplantation
15. Drug-treated gastroparesis, short-bowel syndrome, or any other gastrointestinal condition that may lead to reduced absorption of study drug
16. Serum albumin <3 g/dL
17. History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the subject
18. Prior treatment with FG-4592
19. Use of an investigational medication or treatment, or carryover effect of an investigational treatment expected, during the screening visit, treatment and follow-up period.
20. Use of traditional Chinese medicines (TCM) during the screening visit to Day 1 or plans to use TCM during the study unless approved in advance by the Medical Monitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; TIW dosing, capsule
Experimental: FG-4592; Active Drug	Drug: FG-4592; TIW dosing, capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum change in hemoglobin by Week 9 from baseline	Week 9

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects achieving a target Hb level ≥11 g/dL by Weeks 5,6,7,8 and 9.	Week 9
Proportion of subjects with a Hb increase from baseline ≥1.0 g/dL.	Week 9

Collaborators and Investigators

• Sponsor: FibroGen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: May 11, 2012
• First Submitted That Met QC Criteria: May 14, 2012
• First Posted (Estimate): May 16, 2012

Study Record Updates

• Last Update Posted (Estimate): March 3, 2014
• Last Update Submitted That Met QC Criteria: February 27, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Anemia; Renal
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia
• Other Study ID Numbers: FGCL-4592-047