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Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis

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ClinicalTrials.gov Identifier: NCT01147666
Recruitment Status : Completed
First Posted : June 22, 2010
Last Update Posted : March 19, 2014
Sponsor:
Information provided by (Responsible Party):
FibroGen

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

Condition or disease Intervention/treatment Phase
End Stage Renal Disease Anemia Drug: FG-4592 Drug: Epoetin Alfa Other: Placebo Phase 2

Detailed Description:
Dose ranging study with consecutive cohorts in two subject populations: patients normally responding to current anemia treatment (epoetin alfa) ("normoresponders") and patients not responding well to current treatment ("hyporesponders"). Normoresponders are randomized to study drug FG-4592 or epoetin alfa; hyporesponders are randomized to study drug FG-4592 or epoetin alfa or placebo. 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 161 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Study Start Date : March 2010
Actual Primary Completion Date : October 2012
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Population A; Experimental Drug
Patients responding normally to current treatment
Drug: FG-4592
Different dose levels

Active Comparator: Population A; Active Comparator
Patients responding normally to current treatment
Drug: Epoetin Alfa
Per current label instruction

Experimental: Population B; Experimental Drug
Patients not responding well to current treatment
Drug: FG-4592
Different dose levels

Active Comparator: Population B; Active Comparator
Patients not responding well to current treatment
Drug: Epoetin Alfa
Per current label instruction

Placebo Comparator: Population B; Placebo Comparator
Patients not responding well to current treatment
Other: Placebo
Inactive capsules matching appearance of FG-4592 capsules




Primary Outcome Measures :
  1. Hemoglobin maintenance using various FG-4592 dosing regimens [ Time Frame: week 6 and 17-20 ]

    Outcome measure 1: Number (%) of subjects with hemoglobin levels at Week 6 within -0.5 g/dL from baseline

    Outcome measure 2: Number (%) of subjects with hemoglobin greater than or equal to 11 g/dL at Weeks 17, 18, 19 and 20



Secondary Outcome Measures :
  1. Evaluate dose adjustments to maintain hemoglobin in ESRD patients [ Time Frame: 6 weeks; 19 weeks ]
    Outcome measure: Number of dose adjustments required during the dosing period

  2. Estimate pharmacokinetic and pharmacodynamic parameters [ Time Frame: 19 weeks ]

    Outcome measure 1: trough plasma FG-4592 concentration at week 1, 4 and 6 in all subjects

    Outcome measure 2: plasma FG-4592 concentration and EPO concentration at various hours after dosing in a subset of subjects




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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Age 18 to 75 years
  2. End-stage renal disease (ESRD) and receiving maintenance hemodialysis
  3. Two most recent hemoglobin values obtained during screening period must be within the ranges set below:

    • Croup A. Normoresponder Criteria: Hb range in the 8 weeks prior to randomization within 9.0 to 13.5 g/dL
    • Group B. Hyporesponder Criteria: Hb range in the 8 weeks prior to randomization within 8.5 to 13.5 g/dL
  4. Epoetin alfa, dose requirements:

    • Group A. Normoresponder Criteria - Cohorts A-1 to A-12: Stable IV epoetin alfa dose at baseline (i.e., no more than a 30% fluctuation in the weekly dose) during the 4 weeks prior to study Day -3

      • Cohorts A-1 to A-4: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 85 IU/kg/dose, three times a week (TIW); weekly dose between 75 and 255 IU/kg/week
      • Cohort A-5: Current and previous (past 4 weeks) epoetin alfa dose range =/>85 to 115 IU/kg/dose, TIW; total weekly dose between 255 and 335 IU/kg/week
      • Cohort A-9: Current and previous (past 4 weeks) epoetin alfa dose range =/>85 to 150 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week
      • Cohorts A-6 to A-8: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 115 IU/kg/dose, TIW, and two times a week (BIW); total weekly dose between 75 and 345 IU/kg/week
      • Cohorts A-10 to A-12: Optional cohorts TBD, dosing frequency and dose range to be determined by sponsor
    • Group B. Hyporesponder Criteria:

      • Cohort B-1 (completed): Current and previous (past 4 weeks) epoetin alfa dose range 125 to 400 IU/kg/dose, TIW; weekly dose between 375 and 1200 IU/kg/week
      • Cohort B-2 to B-4: Current and previous (past 4 weeks) epoetin alfa dose range >115 IU/kg/dose, TIW; total weekly dose >345 IU/kg/week no requirement for stability of epoetin alfa doses
  5. Complete Blood Count (CBC), Hematology, liver function blood tests, serum folate and vitamin B12 within acceptable limits
  6. Absence of active or chronic gastrointestinal bleeding
  7. hsCRP <60 mg/L for normoresponders Cohorts A-8 through A-12 enrolled under Amendment 3; no hsCRP criteria for hyporesponders
  8. Body weight: 40 to 140 kg (dry weight)
  9. Body mass index (BMI): 18 to 45 kg/m2
  10. Dialysis vascular access via native arteriovenous fistula or synthetic graft, or permanent (tunneled) catheter (not via temporary catheter); permanent and temporary catheters, however, are still prohibited in Cohort A-5

Key Exclusion Criteria:

  1. Anticipated change in hemodialysis prescription
  2. Any clinically significant infection or evidence of an underlying infection
  3. Positive for any of the following: Human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); or 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 that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
  7. History of myelodysplastic syndrome
  8. History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric
  9. Active hemolysis or diagnosis of hemolytic syndrome
  10. Known bone marrow fibrosis
  11. Uncontrolled or symptomatic secondary hyperparathyroidism
  12. Any prior organ transplantation
  13. Drug-treated gastroparesis or short-bowel syndrome
  14. History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the subject
  15. Prior treatment with FG-4592
  16. Diagnosis or suspicion of renal cell carcinoma
  17. RBC transfusion within 12 weeks prior to Day 1, or anticipated need for RBC transfusion during the dosing period
  18. IV iron supplement within 2 weeks prior to Day 1 and/or unwilling to withhold IV iron during the dosing/Treatment period

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01147666


  Show 25 Study Locations
Sponsors and Collaborators
FibroGen
Investigators
Study Director: Marietta Franco FibroGen

Responsible Party: FibroGen
ClinicalTrials.gov Identifier: NCT01147666     History of Changes
Other Study ID Numbers: FGCL-4592-040
First Posted: June 22, 2010    Key Record Dates
Last Update Posted: March 19, 2014
Last Verified: March 2014

Keywords provided by FibroGen:
Kidney
End Stage Renal Disease
ESRD
Chronic Kidney Disease
CKD
Renal
Anemia
Oral anemia treatment
Hemoglobin levels
Blood count
Erythropoietin
Hemodialysis
Normoresponder
Hyporesponder

Additional relevant MeSH terms:
Anemia
Kidney Diseases
Kidney Failure, Chronic
Hematologic Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Epoetin Alfa
Hematinics