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

Primary Purpose

End Stage Renal Disease, Anemia

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Roxadustat

Epoetin Alfa

Placebo

About this trial

This is an interventional treatment trial for End Stage Renal Disease focused on measuring Kidney, End Stage Renal Disease, ESRD, Chronic Kidney Disease, CKD, Renal, Anemia, Oral anemia treatment, Hemoglobin levels, Blood count, Erythropoietin, Hemodialysis, Normoresponder, Hyporesponder

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
1. 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
2. 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
3. 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
4. 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
5. 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:
1. 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
2. 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Placebo Comparator

Arm Label

Cohort A-1 (Roxadustat 1.0 mg/kg TIW)

Cohort A-2 (Roxadustat 1.5 mg/kg TIW)

Cohort A-3 (Roxadustat 2.0 mg/kg TIW)

Cohort A-4 (Roxadustat 1.8 mg/kg TIW)

Cohort A-5 (Roxadustat 1.8 mg/kg TIW)

Cohort A-6 (Roxadustat 1.3 mg/kg TIW)

Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)

Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)

Cohort A-9 (Roxadustat 2.0 mg/kg)

Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)

Cohorts A (Epoetin Alfa)

Cohort B-1 (Roxadustat 1.5 mg/kg TIW)

Cohort B-2 (Roxadustat 2.0 mg/kg TIW)

Cohort B (Epoetin Alfa)

Cohort B (Placebo)

Arm Description

Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.0 milligrams (mg)/kg, administered orally 3 times weekly (TIW) in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 grams [g]/deciliter [dL]) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who have not completed 6-week treatment at the time of Amendment 2, will continue treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants will receive roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants will receive roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants will receive roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Normoresponsive participants will receive IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing will occur on dialysis days in each Cohort A. Dose adjustment will be per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.

Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who have not completed 6-week treatment at the time of Amendment 2, will continue treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Hyporesponsive participants will receive IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing will occur on dialysis days in each Cohort B. Dose adjustment will be per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.

Hyporesponsive participants will receive placebo matched to roxadustat, administered orally TIW for 19 weeks.

Outcomes

Primary Outcome Measures

Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only

Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. Last observation carried forward (LOCF) method was used to impute missing values.

Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks

Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

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

The average of the mean Hb values that were above 11 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

Secondary Outcome Measures

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)

The average of the mean Hb values that were within 11-13 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

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)

The average of the mean Hb values that were within 10-13 g/dL at Weeks 17, 18, 19, and 20 are presented. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. LOCF method was used to impute missing values.

Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks

Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks

Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only

Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks

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

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

Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level

Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

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

Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks

Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.

Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks

Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.

Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks

Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks

Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6

The rate of rise was computed as the slope of the regression line of change in Hb level (in g/dL) vs. time (in weeks) using Random Coefficient Model. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

Trough Plasma Concentration of Roxadustat and Epoetin Alfa

Full Information

NCT ID

NCT01147666

First Posted

May 20, 2010

Last Updated

December 14, 2021

Sponsor

FibroGen

Collaborators

AstraZeneca, Astellas Pharma Inc

1. Study Identification

Unique Protocol Identification Number

NCT01147666

Brief Title

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

Official Title

A Phase 2, Randomized, Open-Label Active-Comparator (Epoetin Alfa) and Single-Blind Placebo-Controlled, Dose-Ranging Safety and Exploratory Efficacy Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

May 17, 2010 (Actual)

Primary Completion Date

October 15, 2012 (Actual)

Study Completion Date

October 15, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

FibroGen

Collaborators

AstraZeneca, Astellas Pharma Inc

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed Description

Dose ranging study with consecutive cohorts in two participant populations: participants normally responding to current anemia treatment (epoetin alfa) ("normoresponders": participants with baseline epoetin alfa dose at study entry 75 to 450 international units [IU]/kilograms [kg]/week) and participants not responding well to current treatment ("hyporesponders": participants with maintenance epoetin alfa dose above 450 IU/kg/week). Normoresponders are randomized to study drug roxadustat or epoetin alfa at a ratio of 3:1; hyporesponders are randomized to study drug roxadustat or epoetin alfa or placebo at a ratio of 2:1:1. The study objectives are to demonstrate that roxadustat 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

End Stage Renal Disease, Anemia

Keywords

Kidney, End Stage Renal Disease, ESRD, Chronic Kidney Disease, CKD, Renal, Anemia, Oral anemia treatment, Hemoglobin levels, Blood count, Erythropoietin, Hemodialysis, Normoresponder, Hyporesponder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

161 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort A-1 (Roxadustat 1.0 mg/kg TIW)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A-2 (Roxadustat 1.5 mg/kg TIW)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A-3 (Roxadustat 2.0 mg/kg TIW)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A-4 (Roxadustat 1.8 mg/kg TIW)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A-5 (Roxadustat 1.8 mg/kg TIW)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A-6 (Roxadustat 1.3 mg/kg TIW)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)

Arm Type

Experimental

Arm Description

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants will receive roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Arm Title

Cohort A-9 (Roxadustat 2.0 mg/kg)

Arm Type

Experimental

Arm Description

Arm Title

Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)

Arm Type

Experimental

Arm Description

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants will receive roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Arm Title

Cohorts A (Epoetin Alfa)

Arm Type

Active Comparator

Arm Description

Arm Title

Cohort B-1 (Roxadustat 1.5 mg/kg TIW)

Arm Type

Experimental

Arm Description

Arm Title

Cohort B-2 (Roxadustat 2.0 mg/kg TIW)

Arm Type

Experimental

Arm Description

Arm Title

Cohort B (Epoetin Alfa)

Arm Type

Active Comparator

Arm Description

Arm Title

Cohort B (Placebo)

Arm Type

Placebo Comparator

Arm Description

Hyporesponsive participants will receive placebo matched to roxadustat, administered orally TIW for 19 weeks.

Intervention Type

Drug

Intervention Name(s)

Roxadustat

Other Intervention Name(s)

FG-4592

Intervention Description

Roxadustat will be administered per dose and schedule specified in the arms.

Intervention Type

Drug

Intervention Name(s)

Epoetin Alfa

Intervention Description

Epoetin Alfa will be administered per dose and schedule specified in the arms.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo matching to roxadustat will be administered per schedule specified in the arm.

Primary Outcome Measure Information:

Title

Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only

Description

Time Frame

Week 7

Title

Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks

Description

Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

Time Frame

Week 7

Title

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

Description

The average of the mean Hb values that were above 11 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

Time Frame

Weeks 17, 18, 19, and 20

Secondary Outcome Measure Information:

Title

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)

Description

The average of the mean Hb values that were within 11-13 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

Time Frame

Weeks 17, 18, 19, and 20

Title

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)

Description

Time Frame

Weeks 17, 18, 19, and 20

Title

Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks

Description

Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

Time Frame

Baseline, Week 7

Title

Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks

Description

Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

Time Frame

Baseline, Weeks 8, 10, 12, 14, 17, 19, and 20

Title

Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only

Description

Time Frame

Baseline up to Week 6

Title

Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks

Description

Time Frame

Baseline up to Week 19

Title

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

Time Frame

Week 7

Title

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

Time Frame

Week 7

Title

Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level

Description

Time Frame

Week 7

Title

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

Description

Time Frame

Weeks 8, 10, 12, 14, 17, 19, and 20

Title

Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks

Description

Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.

Time Frame

Baseline up to Week 6

Title

Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks

Description

Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.

Time Frame

Baseline up to Week 19

Title

Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks

Time Frame

Baseline up to Week 6

Title

Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks

Time Frame

Baseline up to Week 19

Title

Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6

Description

Time Frame

Baseline up to Week 6

Title

Trough Plasma Concentration of Roxadustat and Epoetin Alfa

Time Frame

Predose, 4, 8, 12, 24, 48, and 72 hours postdose at Weeks 1 and 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marietta Franco

Organizational Affiliation

FibroGen

Official's Role

Study Director

Facility Information:

City

Tempe

State/Province

Arizona

Country

United States

City

Pine Bluff

State/Province

Arkansas

Country

United States

City

Azusa

State/Province

California

Country

United States

City

Los Angeles

State/Province

California

Country

United States

City

Northridge

State/Province

California

Country

United States

City

Ontario

State/Province

California

Country

United States

City

Paramount

State/Province

California

Country

United States

City

Yuba City

State/Province

California

Country

United States

City

Miami

State/Province

Florida

Country

United States

City

Pembroke Pines

State/Province

Florida

Country

United States

City

Honolulu

State/Province

Hawaii

Country

United States

City

Louisville

State/Province

Kentucky

Country

United States

City

Detroit

State/Province

Michigan

Country

United States

City

Kansas City

State/Province

Missouri

Country

United States

City

Paterson

State/Province

New Jersey

Country

United States

City

New York

State/Province

New York

Country

United States

City

Rosedale

State/Province

New York

Country

United States

City

Williamsville

State/Province

New York

Country

United States

City

Toledo

State/Province

Ohio

Country

United States

City

Orangeburg

State/Province

South Carolina

Country

United States

City

Arlington

State/Province

Texas

Country

United States

City

Fort Worth

State/Province

Texas

Country

United States

City

Houston

State/Province

Texas

Country

United States

City

San Antonio

State/Province

Texas

Country

United States

City

Fairfax

State/Province

Virginia

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

36005278

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.

Results Reference

derived

Learn more about this trial

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

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