Clinical trial NCT01596855: Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis in China
Official title: A Phase 2, Randomized, Open-Label Active-Comparator (Epoetin Alfa) Dose-Ranging Safety and Exploratory Efficacy Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis (HD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia in End Stage Renal Disease
Keywords: Anemia
Renal
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
Collaborators: name: Ruijin Hospital
name: RenJi Hospital
name: Chang Zheng Hospital
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Peking University First Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: First Affiliated Hospital of Zhejiang University
name: Peking Union Medical College Hospital
name: Shenzhen People's Hospital
First posted: 2012-05-11
Enrollment: 96
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: The purpose of this study is to evaluate the efficacy and safety of FG-4592 in maintaining and/or correcting hemoglobin (Hb) given to subjects with End Stage Renal Disease (ESRD) on maintenance hemodialysis and receiving epoetin alfa.

Detailed description: Dose ranging study with three consecutive dose escalation cohorts. The study objectives are to demonstrate that FG-4592 is effective in maintaining hemoglobin (Hb) levels when converting from epoetin alfa and to establish optimum starting doses and dose adjustment regimens for Hb maintenance.

Eligibility criteria: Inclusion Criteria:

1. Subject has voluntarily signed and dated an informed consent form
2. Age 18 to 75 years
3. End-stage renal disease (ESRD) and receiving maintenance hemodialysis TIW for ≥4 months prior to Day 1
4. Hemoglobin (Hb) values in 4 screening visits and the mean Hb must be between 9.0 and 12.0 g/dL (inclusive), and the difference between them must be ≤1.5 g/dL.
5. Stable doses of IV or Subcutaneous injection of epoetin alfa, defined as follows:

   * Epoetin alfa dose range for 6 weeks prior to Day -7:

     3000 to 20,000 IU/week
   * Stable doses of epoetin alfa (i.e., the maximum epoetin alfa dose does not exceed 130% of the lowest dose of epoetin alfa taken in this period)
6. Complete Blood Count (CBC), Hematology, liver function blood tests within acceptable limits
7. Serum folate and vitamin B12 levels above the lower limit of normal (LLN)
8. Body weight: 40 to 100 kg (dry weight) inclusive
9. Body mass index (BMI): 16 to 38 kg/m2 inclusive
10. HD subjects: dialysis vascular access via native arteriovenous fistula or synthetic graft (not via catheter)

Exclusion Criteria:

1. Anticipated change in hemodialysis prescription or access during the screening or dosing period of the study
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. History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the subject
17. Prior treatment with FG-4592
18. 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

Primary outcomes:
measure: Hemoglobin maintenance using FG-4592 dosing regimen in ESRD subjects. Number of subjects who hemoglobin levels are maintained at no lower than 0.5 g/dL below their mean baseline value during weeks 6 and 7.
timeFrame: Week 7
Secondary outcomes:
measure: Number (%) of subjects whose hemoglobin levels are between 9.0 and 13.0 g/dL at Weeks 3, 4, 5, 6 and 7.
timeFrame: Week 7
measure: Number (%) of subjects whose hemoglobin levels at Weeks 3, 4, 5, 6 and 7 are greater than or equal to their baseline level.
timeFrame: Week 7
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Guangzhou
country: China
facility: First Affiliated Hospital, Sun Yat-Sen University
city: Hangzhou
country: China
facility: Zhejiang University No 1. Hospital
city: Shanghai
country: China
facility: Chang Zheng Hospital
city: Shanghai
country: China
facility: Renji Hospital
city: Shanghai
country: China
facility: RuiJin Hospital
city: Shanghai
country: China
facility: XinHua Hospital
city: Shenzhen
country: China
facility: ShenZhen People's Hospital
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.