Phase 2 N=161 Randomized Double-blind Treatment

Study of Roxadustat (FG-4592) in Participants With End-Stage Renal Disease Receiving Maintenance Hemodialysis

End Stage Renal Disease · Anemia

Bottom Line

View on ClinicalTrials.gov: NCT01147666 ↗

Enrolled (actual)

161

Serious AEs

23.0%

Results posted

Jan 2022

Primary outcome: Primary: Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only — 4; 8; 7; 4 Participants — p=1.0000

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Roxadustat (Drug); Epoetin Alfa (Drug); Placebo (Other)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Kyntra Bio
Primary completion: Oct 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only	4; 8; 7; 4; 3	1.0000
PRIMARY Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks	0; 1; 2; 0	1.0000
PRIMARY Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks	4; 4; 6; 5; 6; 2	—
SECONDARY Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)	4; 1; 6; 5; 6; 2	—
SECONDARY Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)	5; 2; 10; 10; 7; 2	—
SECONDARY Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks	-0.40; 0.91; 0.71; 0.25; -0.15; -0.18	—
SECONDARY Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks	0.49; 0.08; 0.01; -0.49; -0.29; 0.05	—
SECONDARY Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only	0; 3; 0; 0; 9; 0	—
SECONDARY Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks	2; 5; 5; 4; 7; 1	—
SECONDARY Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks	3; 3; 5; 5; 4; 3	—
SECONDARY Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks	3; 4; 3; 6; 6; 0	—
SECONDARY Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level	3; 7; 6; 3; 2	—
SECONDARY Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level	3; 6; 4; 4; 4; 1	—
SECONDARY Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks	2; 2; 3; 4; 2; 3	—
SECONDARY Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks	4; 2; 3; 2; 3; 0	—
SECONDARY Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks	0; 0; 0; 1; 0; 2	—
SECONDARY Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks	0; 0; 2; 1; 2; 1	—
SECONDARY Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6	-0.0135; 0.1926; 0.1682; -0.0220; -0.1267	—
SECONDARY Trough Plasma Concentration of Roxadustat and Epoetin Alfa	—	—

Summary

The primary objective of this study is to evaluate the efficacy and safety of roxadustat in participants with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) therapy, previously treated with intravenous (IV) epoetin alfa.

Eligibility Criteria

Key Inclusion Criteria

ESRD and receiving maintenance HD TIW for ≥4 months prior to Day 1
Two most recent Hb values obtained during screening period must be within the ranges set below:

i) Group A. Normoresponder Criteria: Hb range in the 8 weeks prior to randomization within 9.0 to 13.5 g/dL ii) Group B. Hyporesponder Criteria: Hb range in the 8 weeks prior to randomization within 8.5 to 13.5 g/dL

Epoetin alfa, dose requirements:

i) Group A. Normoresponder Criteria - Cohorts A-1 to A-12: Stable IV epoetin alfa dose at baseline (that is, 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, 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 450 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 to be decided (TBD), dosing frequency and dose range to be determined by sponsor ii) 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
Complete Blood Count (CBC), Hematology, liver function blood tests, serum folate and vitamin B12 within acceptable limits
Absence of active or chronic gastrointestinal bleeding
High sensitivity C-reactive protein (hsCRP) <60 mg/liter for normoresponders Cohorts A-8 through A-12 enrolled under Amendment 3; no hsCRP criteria for hyporesponders
Body weight: 40 to 140 kg (dry weight)
Body mass index (BMI): 18 to 45 kg/meter square (m^2)
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

Anticipated change in HD prescription
Any clinically significant infection or evidence of an underlying infection
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
New York Heart Association Class III or IV congestive heart failure
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 myelodysplastic syndrome
History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric
Active hemolysis or diagnosis of hemolytic syndrome
Known bone marrow fibrosis
Uncontrolled or symptomatic secondary hyperparathyroidism
Any prior organ transplantation
Drug-treated gastroparesis or short-bowel syndrome
History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the participant
Prior treatment with roxadustat
Diagnosis or suspicion of renal cell carcinoma
Red blood cell (RBC) transfusion within 12 weeks prior to Day 1, or anticipated need for RBC transfusion during the dosing period
IV iron supplement within 2 weeks prior to Day 1 and/or unwilling to withhold IV iron during the dosing/treatment period

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01147666). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.