Back to results

Study of Roxadustat in Non-Dialysis Chronic Kidney Disease Participants With Anemia

Primary Purpose

Chronic Kidney Disease, Anemia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Roxadustat

About this trial

This is an interventional treatment trial for Chronic Kidney Disease focused on measuring Kidney, Chronic Kidney Disease, CKD, Renal, Anemia, Oral anemia treatment, Hemoglobin levels, Erythropoietin, Blood count, Predialysis, Pre-dialysis, Hb, Non-dialysis

Eligibility Criteria

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

Inclusion Criteria:

Age 18 to 75 years
Chronic kidney disease, not receiving dialysis
Body weight 45 to 140 kg

Exclusion Criteria:

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
Myocardial infarction or acute coronary syndrome within 12 weeks prior to randomization
History of malignancy
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, multiple myeloma, or pure red cell aplasia
History of hemosiderosis, hemochromatosis or polycystic kidney disease
Active hemolysis or diagnosis of hemolytic syndrome
Uncontrolled or symptomatic secondary hyperparathyroidism
Seizure disorder or receiving anti-epilepsy medication
Known bone marrow fibrosis
Any prior or scheduled organ transplant
Prior treatment with roxadustat or any hypoxia-inducible factor prolyl hydroxylase inhibitor
History of alcohol or drug abuse

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Cohort A: Roxadustat Tiered, Weight Based Dosing TIW

Cohort B: Roxadustat Tiered, Weight Based Dosing TIW then BIW

Cohort C: Roxadustat at 50 mg TIW

Cohort D: Roxadustat at 100 mg TIW

Cohort E: Roxadustat Tiered, Weight Based Dosing BIW then QW

Cohort F: Roxadustat at 70 mg BIW then QW

Arm Description

Participants will receive roxadustat capsules, administered orally 3 times weekly (TIW) for 16 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight [45 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 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL.

Participants will receive roxadustat capsules orally for 16 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight [45 to 60 kg], medium-weight [>60 to 90 kg], and heavy-weight [>90 to 140 kg] participants will receive 60, 100, and 140 mg roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from TIW to 2 times a week (BIW) at the time of the initial Hb response.

Participants will receive roxadustat capsules at 50 mg, administered orally TIW for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 10.5-12 g/dL.

Participants will receive roxadustat capsules at 100 mg, administered orally TIW for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 10.5-12 g/dL.

Participants will receive roxadustat capsules for 24 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight [45 to 60 kg], medium-weight [>60 to 90 kg], and heavy-weight [>90 to 140 kg] participants will receive 70, 100, and 150 mg roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.5 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from BIW to 1 time a week (QW) at the time of the initial Hb response.

Participants will receive roxadustat capsules at 70 mg for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.5 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from TIW to BIW at the time of the initial Hb response. Then after >8 weeks of stable Hb, dose frequency will be reduced from BIW to QW.

Outcomes

Primary Outcome Measures

Number (%) of Participants With an Hb Response by Week 17

An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL.

Secondary Outcome Measures

Number (%) of Participants With an Hb Response by Weeks 5, 9, 13, 17, 21, and 25

An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL.

Change From Baseline in Hb at Weeks 5, 9, 13, 17, 21, and 25

Baseline is defined as the mean of the last 3 available values predose.

Number (%) of Participants With Mean Hb Between 11-12, 11-13, and 10.5-13 g/dL During Weeks 5-8, 9-12, 9-16, 13-16, 17-20, 17-24, 21-24, and 25-28

Participants can have a Hb value reported for more than 1 of the categories (11-12, 11-13, and 10.5-13 g/dL) during the week intervals since these categories are not mutually exclusive.

Number (%) of Participants With 2 Consecutive Hb Values Between 11-12, 11-13, and 10.5-13 g/dL During Weeks 5-8, 9-12, 13-16, 9-16, 17-20, 17-24, 21-24, and 25-28

Number (%) of Participants Who Achieve Maximum Hb Between 11-12, 11-13, and 10.5-13 g/dL by Weeks 5, 9, 13, 17, 21, and 25

Participants can have a Hb value for the same category (11-12, 11-13, or 10.5-13 g/dL) reported for multiple weeks.

Number (%) of Participants With Maximum Hb <11, >12, >13, and >14 g/dL During Weeks 5-8, 9-12, 9-16, 13-16, 17-20, 17-24, 21-24, and 25-28

Median Time to Hb Response: Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL

Median time to response was estimated using Kaplan Meier method, Cohort A and B censored at Week 17, Cohort C, D, E, and F censored at Week 25. The median number of days presented was calculated from Baseline to the day the Hb response was achieved.

Median Initial Hb Responsive Time: Time to Initial Hb Increase ≥1.0 g/dL From Baseline

Median time to response was estimated using Kaplan Meier method; Cohort A and B censored at Week 17 and Cohort C, D, E, and F censored at Week 25. The median number of days presented was calculated from Baseline to the day the Hb response was achieved.

Median Initial Hb Responsive Dose: Dose at Which Initial Hb Increases to ≥1.0 g/dL From Baseline

Change in Hb After Reaching a Hb Response of ≥11.0 g/dL and an Increase in Hb by ≥1.0 g/dL by Week

Mean Hb Values From Participants Who Reached Hb >11.0 g/dL in the Hb 11-12, 11-13, and 10.5-13 g/dL Categories

Mean of Weekly Hb Values <10.5, >13, and >14 g/dL During Weeks 13-17 and 18-25

The mean percentage of the scheduled weekly Hb values that were <10.5, >13, and >14 g/dL during Weeks 13-17 and 18-25 is presented.

Number (%) of Participants Requiring Rescue Therapy

Rescue treatment included recombinant erythropoiesis-stimulating agent (ESA), red blood cell transfusion (in the absence of a known bleeding episode or surgical blood loss), or intravenous (IV) Iron

Number (%) of Participants Requiring Therapeutic Phlebotomy

Number (%) of Participants Withdrawn From the Study Due to Inadequate Efficacy

Number (%) of Participants With Dose Changes During Weeks 1-4, 5-12, 13-16, and 17-24

Dose changes include dose reductions, dose increases, and dose holds.

Weekly Total Dose and Cumulative Total Dose (mg/kg) When First Achieving Hb Response (Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL)

Mean Weekly Dose After Achieving First Hb Response (Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL)

Change From Baseline in Hb Stratified by Baseline Ferritin >100 Nanograms/Milliliter (ng/mL) and Transferrin Saturation >20% at Week 16 and Week 24

Baseline was defined as the mean of the last 3 available values predose.

Full Information

NCT ID

NCT01244763

First Posted

November 16, 2010

Last Updated

January 17, 2022

Sponsor

FibroGen

Collaborators

Astellas Pharma Inc

1. Study Identification

Unique Protocol Identification Number

NCT01244763

Brief Title

Study of Roxadustat in Non-Dialysis Chronic Kidney Disease Participants With Anemia

Official Title

A Phase 2, Randomized, Open-Label, Dose Titration, Efficacy and Safety Study of FG-4592 (Roxadustat) in Non-Dialysis Chronic Kidney Disease Patients With Anemia

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Completed

Study Start Date

October 29, 2010 (Actual)

Primary Completion Date

June 13, 2012 (Actual)

Study Completion Date

June 13, 2012 (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 primary purpose of this study is to evaluate efficacy and safety of roxadustat in the correction of anemia in participants with non-dialysis chronic kidney disease.

6. Conditions and Keywords

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

Chronic Kidney Disease, Anemia

Keywords

Kidney, Chronic Kidney Disease, CKD, Renal, Anemia, Oral anemia treatment, Hemoglobin levels, Erythropoietin, Blood count, Predialysis, Pre-dialysis, Hb, Non-dialysis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

145 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort A: Roxadustat Tiered, Weight Based Dosing TIW

Arm Type

Experimental

Arm Description

Arm Title

Cohort B: Roxadustat Tiered, Weight Based Dosing TIW then BIW

Arm Type

Experimental

Arm Description

Arm Title

Cohort C: Roxadustat at 50 mg TIW

Arm Type

Experimental

Arm Description

Arm Title

Cohort D: Roxadustat at 100 mg TIW

Arm Type

Experimental

Arm Description

Arm Title

Cohort E: Roxadustat Tiered, Weight Based Dosing BIW then QW

Arm Type

Experimental

Arm Description

Arm Title

Cohort F: Roxadustat at 70 mg BIW then QW

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Roxadustat

Other Intervention Name(s)

FG-4592

Intervention Description

Oral capsule

Primary Outcome Measure Information:

Title

Number (%) of Participants With an Hb Response by Week 17

Description

An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL.

Time Frame

Up to Week 17

Secondary Outcome Measure Information:

Title

Number (%) of Participants With an Hb Response by Weeks 5, 9, 13, 17, 21, and 25

Description

An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL.

Time Frame

Up to Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only)

Title

Change From Baseline in Hb at Weeks 5, 9, 13, 17, 21, and 25

Description

Baseline is defined as the mean of the last 3 available values predose.

Time Frame

Baseline, Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only)

Title

Number (%) of Participants With Mean Hb Between 11-12, 11-13, and 10.5-13 g/dL During Weeks 5-8, 9-12, 9-16, 13-16, 17-20, 17-24, 21-24, and 25-28

Description

Participants can have a Hb value reported for more than 1 of the categories (11-12, 11-13, and 10.5-13 g/dL) during the week intervals since these categories are not mutually exclusive.

Time Frame

Weeks 5-8, 9-12, 9-16, 13-16, and 17-20 (all cohorts) and Weeks 17-24, 21-24, and 25-28 (24-week treatment cohorts only)

Title

Number (%) of Participants With 2 Consecutive Hb Values Between 11-12, 11-13, and 10.5-13 g/dL During Weeks 5-8, 9-12, 13-16, 9-16, 17-20, 17-24, 21-24, and 25-28

Time Frame

Weeks 5-8, 9-12, 9-16, 13-16, and 17-20 (all cohorts) and Weeks 17-24, 21-24, and 25-28 (24-week treatment cohorts only)

Title

Number (%) of Participants Who Achieve Maximum Hb Between 11-12, 11-13, and 10.5-13 g/dL by Weeks 5, 9, 13, 17, 21, and 25

Description

Participants can have a Hb value for the same category (11-12, 11-13, or 10.5-13 g/dL) reported for multiple weeks.

Time Frame

Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only)

Title

Number (%) of Participants With Maximum Hb <11, >12, >13, and >14 g/dL During Weeks 5-8, 9-12, 9-16, 13-16, 17-20, 17-24, 21-24, and 25-28

Time Frame

Weeks 5-8, 9-12, 9-16, 13-16, and 17-20 (all cohorts) and Weeks 17-24, 21-24, and 25-28 (24-week treatment cohorts only)

Title

Median Time to Hb Response: Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL

Description

Time Frame

Up to Week 17 (Cohorts A and B) and up to Week 25 (Cohorts C-F)

Title

Median Initial Hb Responsive Time: Time to Initial Hb Increase ≥1.0 g/dL From Baseline

Description

Time Frame

Up to Week 17 (Cohorts A and B) and up to Week 25 (Cohorts C, D, E, and F)

Title

Median Initial Hb Responsive Dose: Dose at Which Initial Hb Increases to ≥1.0 g/dL From Baseline

Time Frame

Up to Week 17 (Cohorts A and B) and up to Week 25 (Cohorts C-F)

Title

Change in Hb After Reaching a Hb Response of ≥11.0 g/dL and an Increase in Hb by ≥1.0 g/dL by Week

Time Frame

Cohorts A and B: Weekly through Week 16 (end of treatment), Week 18 (2 weeks posttreatment), and Week 20 (4 weeks posttreatment); Cohorts C-F: Weekly through Week 24 (end of treatment), Week 26 (2 weeks posttreatment), and Week 28 (4 weeks posttreatment)

Title

Mean Hb Values From Participants Who Reached Hb >11.0 g/dL in the Hb 11-12, 11-13, and 10.5-13 g/dL Categories

Time Frame

Cohorts A and B: Weekly through Week 16 (end of treatment [EoT]) and Week 20 (Follow up [4 weeks posttreatment]); Cohorts C-F: Weekly through Week 24 (EoT) and Week 28 (Follow up [4 weeks posttreatment])

Title

Mean of Weekly Hb Values <10.5, >13, and >14 g/dL During Weeks 13-17 and 18-25

Description

The mean percentage of the scheduled weekly Hb values that were <10.5, >13, and >14 g/dL during Weeks 13-17 and 18-25 is presented.

Time Frame

Weeks 13-17 (all cohorts) and 18-25 (24-week treatment cohorts only)

Title

Number (%) of Participants Requiring Rescue Therapy

Description

Rescue treatment included recombinant erythropoiesis-stimulating agent (ESA), red blood cell transfusion (in the absence of a known bleeding episode or surgical blood loss), or intravenous (IV) Iron

Time Frame

Baseline up to Week 28 (end of study)

Title

Number (%) of Participants Requiring Therapeutic Phlebotomy

Time Frame

Baseline up to Week 28 (end of study)

Title

Number (%) of Participants Withdrawn From the Study Due to Inadequate Efficacy

Time Frame

Baseline up to Week 28 (end of study)

Title

Number (%) of Participants With Dose Changes During Weeks 1-4, 5-12, 13-16, and 17-24

Description

Dose changes include dose reductions, dose increases, and dose holds.

Time Frame

Weeks 1-4, 5-12, and 13-16 (all cohorts) and Weeks 17-24 (24-week treatment cohorts only)

Title

Weekly Total Dose and Cumulative Total Dose (mg/kg) When First Achieving Hb Response (Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL)

Time Frame

Cohorts A and B: Weekly through Week 16 (end of treatment); Cohorts C-F: Weekly through Week 24 (end of treatment)

Title

Mean Weekly Dose After Achieving First Hb Response (Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL)

Time Frame

Cohorts A and B: Weekly through Week 16 (end of treatment); Cohorts C-F: Weekly through Week 24 (end of treatment)

Title

Change From Baseline in Hb Stratified by Baseline Ferritin >100 Nanograms/Milliliter (ng/mL) and Transferrin Saturation >20% at Week 16 and Week 24

Description

Baseline was defined as the mean of the last 3 available values predose.

Time Frame

Baseline, Weeks 16 (Cohorts A and B End of Treatment) and Week 24 (Cohorts C-F End of Treatment)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18 to 75 years Chronic kidney disease, not receiving dialysis Body weight 45 to 140 kg Exclusion Criteria: 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 Myocardial infarction or acute coronary syndrome within 12 weeks prior to randomization History of malignancy 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, multiple myeloma, or pure red cell aplasia History of hemosiderosis, hemochromatosis or polycystic kidney disease Active hemolysis or diagnosis of hemolytic syndrome Uncontrolled or symptomatic secondary hyperparathyroidism Seizure disorder or receiving anti-epilepsy medication Known bone marrow fibrosis Any prior or scheduled organ transplant Prior treatment with roxadustat or any hypoxia-inducible factor prolyl hydroxylase inhibitor History of alcohol or drug abuse

Facility Information:

City

Mobile

State/Province

Alabama

Country

United States

City

Pine Bluff

State/Province

Arkansas

Country

United States

City

Azusa

State/Province

California

Country

United States

City

Chula Vista

State/Province

California

Country

United States

City

Downey

State/Province

California

Country

United States

City

Northridge

State/Province

California

Country

United States

City

Paramount

State/Province

California

Country

United States

City

Riverside

State/Province

California

Country

United States

City

Whittier

State/Province

California

Country

United States

City

Yuba City

State/Province

California

Country

United States

City

Fort Lauderdale

State/Province

Florida

Country

United States

City

Lauderdale Lakes

State/Province

Florida

Country

United States

City

Pembroke Pines

State/Province

Florida

Country

United States

City

Tampa

State/Province

Florida

Country

United States

City

Augusta

State/Province

Georgia

Country

United States

City

Meridian

State/Province

Idaho

Country

United States

City

Wichita

State/Province

Kansas

Country

United States

City

Baton Rouge

State/Province

Louisiana

Country

United States

City

Shreveport

State/Province

Louisiana

Country

United States

City

Bethesda

State/Province

Maryland

Country

United States

City

Detroit

State/Province

Michigan

Country

United States

City

Lincoln

State/Province

Nebraska

Country

United States

City

Mount Laurel

State/Province

New Jersey

Country

United States

City

Mineola

State/Province

New York

Country

United States

City

New York

State/Province

New York

Country

United States

City

Asheville

State/Province

North Carolina

Country

United States

City

Raleigh

State/Province

North Carolina

Country

United States

City

Canton

State/Province

Ohio

Country

United States

City

Orangeburg

State/Province

South Carolina

Country

United States

City

Knoxville

State/Province

Tennessee

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

City

Caguas

Country

Puerto Rico

City

Ponce

Country

Puerto Rico

City

San Juan

Country

Puerto Rico

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 in Non-Dialysis Chronic Kidney Disease Participants With Anemia

We'll reach out to this number within 24 hrs