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Study of Roxadustat (FG-4592) to Correct Anemia in Newly Initiated Dialysis Participants Not on Erythropoiesis-Stimulating Agent Treatment

Primary Purpose

Dialysis, Anemia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Roxadustat

Oral Iron

IV Iron

About this trial

This is an interventional treatment trial for Dialysis focused on measuring Kidney, ESRD, Renal, End-Stage Renal Disease, Anemia, Oral anemia treatment, Hemoglobin levels, Hemodialysis, Peritoneal, HD, PD, Hb, Erythropoietin, Blood count

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Arm A + E (Participants on HD): Roxadustat Only, No Iron

Arm B (Participants on HD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg

Arm C (Participants on HD): IV Iron (Ferric Gluconate Complex in Sucrose or Equivalent) 60 mg

Arm D (Participants on PD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg

Arm Description

Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with iron (ferrous fumarate or ferrous gluconate) PO at doses containing elemental iron between 50 and 195 mg daily (depending on the type of iron formulation available in their countries) for 12 weeks.

Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with approximately 60 mg IV iron (ferric gluconate complex in sucrose injection [for example, Ferrlecit®] or equivalent) once a week for 12 weeks.

Participants on PD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with iron (ferrous fumarate or ferrous gluconate) PO at doses containing elemental iron between 50 and 195 mg daily (depending on the type of iron formulation available in their countries) for 12 weeks.

Outcomes

Primary Outcome Measures

Maximum Change From Baseline in Hb During Weeks 3-13

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration. This outcome measure is derived from the maximum change from baseline during Weeks 3-13, without last observation carried forward (LOCF) imputation.

Secondary Outcome Measures

Mean Change From Baseline in Hb During Weeks 2-5, 6-9, and 10-13

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

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

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

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

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

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

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Number of Participants Who Achieved Maximum Hb During Weeks 3-13

Number of Participants With a Maximum Change From Baseline in Hb During Weeks 3-13

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration. The number of participants who fall within the following categories of maximum change are reported: <1 g/dL, ≥1 g/dL, 1 to <2 g/dL, 2 to <3 g/dL, >3 to <4 g/dL, ≥4 g/dL.

Median Time to Hb Response (Increase in Hb by ≥1.0 g/dL From Baseline)

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Weekly Dose at First Hb Response (Increase in Hb by ≥1.0 g/dL From Baseline)

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Number of Participants Requiring Dose Increase at Weeks 5 and 9

Number of participants requiring dose increase due to any reasons is reported.

Number of Participants Requiring Dose Reduction or Dose Discontinuation Due to Excessive Erythropoiesis

Number of participants requiring dose reduction or dose discontinuation due to excessive erythropoiesis is reported.

Change From Baseline in Ferritin at Week 13

Baseline was defined as the average of the last 2 values prior to the first dose administration.

Change From Baseline in Transferrin Saturation (TSAT) at Week 13

Change From Baseline in Reticulocyte Hemoglobin Content at Week 13

Number of Participants With Mean Hb Values 11.0-13.0 g/dL at Weeks 6-9 and 10-13

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

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

Number of Participants With Mean Hb Values in Excess of 13.0 and 14.0 g/dL at Weeks 6-9 and 10-13

Number of Participants With Mean Hb Values <10.0 g/dL at Weeks 6-9 and 10-13

Number of Participants Requiring Rescue Treatment With an Erythropoiesis-Stimulating Agent (ESA), Red Blood Cells (RBC) Transfusion, or IV Iron (Excluding Arm C)

Number of participants requiring rescue treatment with an ESA, RBC transfusion, or IV Iron (Excluding Arm C) was reported.

Number of Participants Requiring Therapeutic Phlebotomy

Number of participants who required therapeutic phlebotomy due to TEAE of abnormal erythropoiesis is reported.

Number of Participants Withdrawn From the Study Due to Inadequate Efficacy

Number of participants withdrawn from the study due to inadequate efficacy is reported.

Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 9 and 13

The SF-36 V2 consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The physical functioning subscore and vitality subscore are reported. The scores ranged from 0 (worst) to 100 (Best). Higher score indicated a better health state. Baseline is defined as the last non-missing value prior to the first dose administration.

Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score at Weeks 9 and 13

FACT-An is composed of 27 core items which assess participant's function in 4 domains and 20 anemia-related items, grouped into 5 subscales as follows: Physical well-being (PWB): 7 items; Social/family well-being (SWB): 7 items; Emotional well-being (EWB): 6 items; Functional well-being (FWB): 7 items; and Anemia: 20 items. All FACT-An items were rated as: 0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much. Each subscale score was the sum of scores for the items in the subscale. The FACT-An total score was the sum of all 5 subscale scores, ranging from 0 (worst) - 188 (best). Higher scores represented better quality of life. Baseline is defined as the last non-missing value prior to the first dose administration.

Number of Participants With Potentially Clinically Significant Laboratory Tests

Criteria for the potential clinical significance included: bilirubin (µmol/L) >1.5 * upper limit of normal (ULN), potassium (mmol/L) >1.2 * ULN, neutrophils (*10^9/L) ≤1, protein (g/L) >1.1 * ULN, leukocytes (*10^9/L) ≤2.5 or ≥15.

Number of Participants With TEAEs

An adverse event (AE) was any untoward medical event in a participant who received study drug whether or not the event is considered drug related. TEAEs were defined as any event that either began or worsened after the first administration of study drug and within 28 days of the last dose. A summary of other nonserious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Full Information

NCT ID

NCT01414075

First Posted

August 9, 2011

Last Updated

September 1, 2021

Sponsor

FibroGen

Collaborators

Astellas Pharma Inc

1. Study Identification

Unique Protocol Identification Number

NCT01414075

Brief Title

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

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

July 21, 2011 (Actual)

Primary Completion Date

January 10, 2013 (Actual)

Study Completion Date

January 10, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

FibroGen

Collaborators

Astellas Pharma Inc

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

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

Dialysis, Anemia

Keywords

Kidney, ESRD, Renal, End-Stage Renal Disease, Anemia, Oral anemia treatment, Hemoglobin levels, Hemodialysis, Peritoneal, HD, PD, Hb, Erythropoietin, Blood count

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A + E (Participants on HD): Roxadustat Only, No Iron

Arm Type

Experimental

Arm Description

Arm Title

Arm B (Participants on HD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg

Arm Type

Experimental

Arm Description

Arm Title

Arm C (Participants on HD): IV Iron (Ferric Gluconate Complex in Sucrose or Equivalent) 60 mg

Arm Type

Experimental

Arm Description

Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with approximately 60 mg IV iron (ferric gluconate complex in sucrose injection [for example, Ferrlecit®] or equivalent) once a week for 12 weeks.

Arm Title

Arm D (Participants on PD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Roxadustat

Other Intervention Name(s)

FG-4592

Intervention Description

Tiered, weight-based dosing per schedule specified in the arm.

Intervention Type

Drug

Intervention Name(s)

Oral Iron

Intervention Description

Administered per oral dose and schedule specified in the arm.

Intervention Type

Drug

Intervention Name(s)

IV Iron

Intervention Description

Administered per IV dose and schedule specified in the arm.

Primary Outcome Measure Information:

Title

Maximum Change From Baseline in Hb During Weeks 3-13

Description

Time Frame

Baseline, Weeks 3-13

Secondary Outcome Measure Information:

Title

Mean Change From Baseline in Hb During Weeks 2-5, 6-9, and 10-13

Description

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Time Frame

Baseline, Weeks 2-5, 6-9, and 10-13

Title

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

Description

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Time Frame

Week 3 to 13

Title

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

Description

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Time Frame

Week 3 to 13

Title

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

Description

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Time Frame

Weeks 5, 9, and 13

Title

Number of Participants Who Achieved Maximum Hb During Weeks 3-13

Time Frame

Weeks 3-13

Title

Number of Participants With a Maximum Change From Baseline in Hb During Weeks 3-13

Description

Time Frame

Baseline, Weeks 3-13

Title

Median Time to Hb Response (Increase in Hb by ≥1.0 g/dL From Baseline)

Description

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Time Frame

Baseline up to Week 13

Title

Weekly Dose at First Hb Response (Increase in Hb by ≥1.0 g/dL From Baseline)

Description

Baseline Hb was defined as the mean of the last 3 central laboratory Hb values prior to the first dose administration.

Time Frame

Baseline up to Week 13

Title

Number of Participants Requiring Dose Increase at Weeks 5 and 9

Description

Number of participants requiring dose increase due to any reasons is reported.

Time Frame

Weeks 5 and 9

Title

Number of Participants Requiring Dose Reduction or Dose Discontinuation Due to Excessive Erythropoiesis

Description

Number of participants requiring dose reduction or dose discontinuation due to excessive erythropoiesis is reported.

Time Frame

Weeks 5 and 9

Title

Change From Baseline in Ferritin at Week 13

Description

Baseline was defined as the average of the last 2 values prior to the first dose administration.

Time Frame

Baseline, Week 13

Title

Change From Baseline in Transferrin Saturation (TSAT) at Week 13

Time Frame

Baseline, Week 13

Title

Change From Baseline in Reticulocyte Hemoglobin Content at Week 13

Time Frame

Baseline, Week 13

Title

Number of Participants With Mean Hb Values 11.0-13.0 g/dL at Weeks 6-9 and 10-13

Time Frame

Weeks 6-9 and 10-13

Title

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

Time Frame

Weeks 10-13

Title

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

Time Frame

Weeks 10-13

Title

Number of Participants With Mean Hb Values in Excess of 13.0 and 14.0 g/dL at Weeks 6-9 and 10-13

Time Frame

Weeks 6-9 and 10-13

Title

Number of Participants With Mean Hb Values <10.0 g/dL at Weeks 6-9 and 10-13

Time Frame

Weeks 6-9 and 10-13

Title

Number of Participants Requiring Rescue Treatment With an Erythropoiesis-Stimulating Agent (ESA), Red Blood Cells (RBC) Transfusion, or IV Iron (Excluding Arm C)

Description

Number of participants requiring rescue treatment with an ESA, RBC transfusion, or IV Iron (Excluding Arm C) was reported.

Time Frame

Baseline up to Week 13

Title

Number of Participants Requiring Therapeutic Phlebotomy

Description

Number of participants who required therapeutic phlebotomy due to TEAE of abnormal erythropoiesis is reported.

Time Frame

Baseline up to Week 13

Title

Number of Participants Withdrawn From the Study Due to Inadequate Efficacy

Description

Number of participants withdrawn from the study due to inadequate efficacy is reported.

Time Frame

Baseline up to Week 16

Title

Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 9 and 13

Description

Time Frame

Baseline, Weeks 9 and 13

Title

Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score at Weeks 9 and 13

Description

Time Frame

Baseline, Weeks 9 and 13

Title

Number of Participants With Potentially Clinically Significant Laboratory Tests

Description

Time Frame

Baseline up to Week 16

Title

Number of Participants With TEAEs

Description

Time Frame

Baseline up to Week 16

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Facility Information:

City

Northridge

State/Province

California

Country

United States

City

Yuba City

State/Province

California

Country

United States

City

Detroit

State/Province

Michigan

Country

United States

City

Hong Kong

Country

Hong Kong

City

Moscow

Country

Russian Federation

City

St. Petersburg

Country

Russian Federation

City

Singapore

Country

Singapore

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

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Study of Roxadustat (FG-4592) to Correct Anemia in Newly Initiated Dialysis Participants Not on Erythropoiesis-Stimulating Agent Treatment

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