Clinical trial NCT01414075: Study of Roxadustat (FG-4592) to Correct Anemia in Newly Initiated Dialysis Participants Not on Erythropoiesis-Stimulating Agent Treatment
Official title: A Phase 2, Randomized, Open-Label, Dose Titration, Safety and Efficacy Study of FG-4592 for the Correction of Anemia in Newly Initiated Dialysis Patients Not on Erythropoiesis-Stimulating Agent Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dialysis
Anemia
Keywords: Kidney
ESRD
Renal
End-Stage Renal Disease
Anemia
Oral anemia treatment
Hemoglobin levels
Hemodialysis
Peritoneal
HD
PD
Hb
Erythropoietin
Blood count
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
First posted: 2011-08-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
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 efficacy and safety of roxadustat in the correction of anemia in participants with end-stage renal disease who recently started dialysis.

Detailed description: Participants on hemodialysis (HD) will be randomized to 3 treatment arms (A, B, and C) of in a 1:1:1 ratio to receive no iron supplementation, oral iron supplementation, and IV iron supplementation, respectively, in addition to roxadustat. At the same time, participants on peritoneal dialysis (PD) will be enrolled into Arm D. Arm E will enroll either HD or PD participants, and is an optional, confirmatory/supplemental treatment arm with flexible dosing and flexible iron supplementation based on the evaluation of data from the previous 4 treatment arms.

Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low weight \[40 to 60 kilograms {kg}\], medium weight \[\>60 to 90 kg\], and heavy weight \[\>90 to 140 kg\] participants will receive 60, 100, and 140 milligrams \[mg\] roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 140, 200, and 300 mg for low, medium, and high weight participants, respectively) during Weeks 5 and 9, depending on the hemoglobin (Hb) level and rate of Hb rise in the previous 4 weeks.

Eligibility criteria: Inclusion Criteria:

* Receiving HD or PD for native kidney end-stage renal disease (ESRD) for 2 weeks to 4 months, prior to randomization
* Mean of the 2 most recent Hb values during the screening period, obtained at least 7 days apart, must be \<10.0 grams (g)/deciliter (dL), with a difference of ≤1.0 g/dL between the 2 values
* Body weight 40 to 140 kilograms (kg)

Exclusion Criteria:

* Previously received erythropoiesis-stimulating agents
* Received IV iron within 4 weeks of randomization
* Received red blood cell transfusion within 8 weeks prior to randomization or anticipated need for transfusion during the treatment period
* Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab)
* History of chronic liver disease
* Clinically significant infection
* New York Heart Association Class III or IV congestive heart failure
* 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, cervical cancer in situ, or resected colonic polyps
* Chronic inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
* History of other blood disorders
* Active hemolysis or diagnosis of hemolytic syndrome
* Known bone marrow fibrosis
* Uncontrolled or symptomatic secondary hyperparathyroidism
* History of alcohol or drug abuse within a year prior to randomization, or anticipated inability to avoid consumption of more than 3 alcoholic beverages per day
* History of allergy or sensitivity to oral or IV iron therapy
* Seizure disorder or receiving anti-epilepsy medication for seizure disorder within 12 weeks prior to randomization
* Pregnant or breast-feeding females

Primary outcomes:
measure: Maximum Change From Baseline in Hb During Weeks 3-13
timeFrame: Baseline, Weeks 3-13
Secondary outcomes:
measure: Mean Change From Baseline in Hb During Weeks 2-5, 6-9, and 10-13
timeFrame: Baseline, Weeks 2-5, 6-9, and 10-13
measure: Number of Participants Whose Maximum Hb Achieved During Treatment Was at Least 1.0 g/dL Increase From Baseline and Was ≥11.0 g/dL
timeFrame: Week 3 to 13
measure: Number of Participants Whose Maximum Hb Achieved During Treatment Was at Least 1.0 g/dL Increase From Baseline and Was ≥10.0 g/dL
timeFrame: Week 3 to 13
measure: Number of Participants With a Hb Response, Defined as an Increase in Hb by ≥1.0 g/dL From Baseline, by Weeks 5, 9, and 13
timeFrame: Weeks 5, 9, and 13
measure: Number of Participants Who Achieved Maximum Hb During Weeks 3-13
timeFrame: Weeks 3-13
measure: Number of Participants With a Maximum Change From Baseline in Hb During Weeks 3-13
timeFrame: Baseline, Weeks 3-13
measure: Median Time to Hb Response (Increase in Hb by ≥1.0 g/dL From Baseline)
timeFrame: Baseline up to Week 13
measure: Weekly Dose at First Hb Response (Increase in Hb by ≥1.0 g/dL From Baseline)
timeFrame: Baseline up to Week 13
measure: Number of Participants Requiring Dose Increase at Weeks 5 and 9
timeFrame: Weeks 5 and 9
measure: Number of Participants Requiring Dose Reduction or Dose Discontinuation Due to Excessive Erythropoiesis
timeFrame: Weeks 5 and 9
measure: Change From Baseline in Ferritin at Week 13
timeFrame: Baseline, Week 13
measure: Change From Baseline in Transferrin Saturation (TSAT) at Week 13
timeFrame: Baseline, Week 13
measure: Change From Baseline in Reticulocyte Hemoglobin Content at Week 13
timeFrame: Baseline, Week 13
measure: Number of Participants With Mean Hb Values 11.0-13.0 g/dL at Weeks 6-9 and 10-13
timeFrame: Weeks 6-9 and 10-13
measure: Number of Participants With Mean Hb Values Within 11.0-13.0 g/dL During Weeks 10-13 Among Those With Maximum Hb ≥11.0 g/dL and Change of Hb ≥1 g/dL
timeFrame: Weeks 10-13
measure: Number of Participants With Mean Hb Values Within 10.0-13.0 g/dL During Weeks 10-13 Among Those With Maximum Hb ≥10.0 g/dL and Change of Hb ≥1 g/dL
timeFrame: Weeks 10-13
measure: Number of Participants With Mean Hb Values in Excess of 13.0 and 14.0 g/dL at Weeks 6-9 and 10-13
timeFrame: Weeks 6-9 and 10-13
measure: Number of Participants With Mean Hb Values <10.0 g/dL at Weeks 6-9 and 10-13
timeFrame: Weeks 6-9 and 10-13
measure: Number of Participants Requiring Rescue Treatment With an Erythropoiesis-Stimulating Agent (ESA), Red Blood Cells (RBC) Transfusion, or IV Iron (Excluding Arm C)
timeFrame: Baseline up to Week 13
measure: Number of Participants Requiring Therapeutic Phlebotomy
timeFrame: Baseline up to Week 13
measure: Number of Participants Withdrawn From the Study Due to Inadequate Efficacy
timeFrame: Baseline up to Week 16
measure: Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 9 and 13
timeFrame: Baseline, Weeks 9 and 13
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score at Weeks 9 and 13
timeFrame: Baseline, Weeks 9 and 13
measure: Number of Participants With Potentially Clinically Significant Laboratory Tests
timeFrame: Baseline up to Week 16
measure: Number of Participants With TEAEs
timeFrame: Baseline up to Week 16
Other outcomes:
Locations:
city: Northridge
country: United States
state: California
city: Yuba City
country: United States
state: California
city: Detroit
country: United States
state: Michigan
city: Hong Kong
country: Hong Kong
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Singapore
country: Singapore
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.