Back to resultsPhase 2 Study of Roxadustat in Participants With Anemia and Chronic Kidney Disease Not Requiring Dialysis
Primary Purpose
Chronic Kidney Disease, Anemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Roxadustat
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Kidney Disease focused on measuring Kidney, Chronic Kidney Disease, CKD, Stage 3 or 4 Chronic Kidney Disease, Renal, Anemia, Oral anemia treatment, Hemoglobin levels, Blood count, Erythropoietin
Eligibility Criteria
Inclusion Criteria:
- 18 to 80 years of age. Participants aged over 75 years but otherwise meet all other participant selection criteria will be evaluated on a case-by-case basis and can be included in this study, per discretion of Sponsor's physician representative such as medical monitor or clinical leader.
- Chronic Kidney Disease Stage 3 or 4 with hemoglobin <11.0 grams (g)/deciliter (dL).
- Normal iron studies.
- Normal folate and vitamin B12 levels.
- Liver function tests within normal limits at screening.
- Absence of active or chronic rectal bleeding.
- Absence of diagnosis of age-related macular degeneration (AMD), diabetic macular edema, or diabetic proliferative retinopathy that is likely to require treatment during the trial.
- Female participants must not be pregnant nor breastfeeding and agree to use acceptable method of contraception.
- Male participants with partners who can have children must agree to use a medically acceptable method of contraception.
Exclusion Criteria:
- Seropositive for HIV.
- History of chronic liver disease.
- History of polycystic kidney disease (PKD).
- Uncontrolled hypertension (diastolic BP >110 millimeter of mercury (mmHg) or systolic BP >170 mmHg at screening).
- New York Heart Association Class III or IV congestive heart failure.
- Recent myocardial infarction or acute coronary syndrome.
- History of myelodysplastic syndrome.
- Any history of malignancy or a known genetic predisposition for developing cancer (for example, with diagnostic markers suggesting a genetic predisposition of cancer) except for curatively resected basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or resected benign colonic polyps.
- Active inflammatory infection or chronic inflammatory disease.
- Any clinically significant and uncontrolled medical condition considered a high risk for participation in an investigational study.
- Blood clots within 4 weeks.
- History of ongoing hemolysis or diagnosis of hemolytic syndrome.
- Known history of bone marrow fibrosis.
- History of hemosiderosis or hemochromatosis.
- Androgen therapy within 12 weeks.
- Red blood cell transfusion within 12 weeks.
- Therapy with an erythropoiesis stimulating agent (ESA) such as human recombinant erythropoietin within the past 60 days.
- Intravenous iron supplementation within the past 60 days.
- Currently taking dapsone or acetaminophen >2.6 g/day.
- History of prior organ transplantation.
- Alcohol consumption greater than 3 or more drinks per day within the past year.
- Use of an investigational medication or participation in an investigational study within 4 weeks preceding Day 1.
- Positive urine toxicology screen for a substance that has not been prescribed for the participant.
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 Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Roxadustat 0.7 mg/kg BIW
Roxadustat 0.7 mg/kg TIW
Roxadustat 1.0 mg/kg BIW
Roxadustat 1.0 mg/kg TIW
Roxadustat 1.5 mg/kg BIW
Roxadustat 1.5 mg/kg TIW
Roxadustat 2.0 mg/kg BIW
Roxadustat 2.0 mg/kg TIW
Placebo
Arm Description
Participants will receive roxadustat 0.7 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.
Participants will receive roxadustat 0.7 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.
Participants will receive roxadustat 1.0 mg/kg BIW orally with doses administered at least 72 hours apart for 29 days.
Participants will receive roxadustat 1.0 mg/kg TIW orally with doses administered at least 48 hours apart for 26 days.
Participants will receive roxadustat 1.5 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.
Participants will receive roxadustat 1.5 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.
Participants will receive roxadustat 2.0 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.
Participants will receive roxadustat 2.0 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.
Participants will receive placebo orally, matching to the roxadustat dose, number of days per week, and duration.
Outcomes
Primary Outcome Measures
Primary Safety Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Treatment Discontinuation (Parts 1 and 2 Combined)
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 defined as an AE beginning after first dose of study drug until 28 days after last dose of study drug or existing AEs that worsened after first dose of study drug until the participant's last study visit. Severe AEs defined as incapacitating, inability to perform usual activities. Drug-related TEAEs defined as TEAEs with possible, probable, or definite relationship to study drug. Serious AE criteria included death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed here. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Day 26-29 (End of Treatment)
Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline was defined as the mean of last 3 available values prior to the first dose.
Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Week 8 (2 Weeks of Follow Up)
Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline is defined as the mean of last 3 available values prior to the first dose.
Secondary Outcome Measures
Number of Participants With a Hemoglobin Response (Not Due to a RBC Transfusion or IV Iron Supplementation During Treatment)
Hb response defined as an increase in Hb from baseline by ≥1.0 g/dL (not due to red blood cell transfusion or IV iron supplementation during treatment). The baseline for Hb was defined as the mean of the last 3 available Hb values obtained prior to the first dose.
Plasma Roxadustat Concentration (Part 2)
Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29
Baseline is defined as the last value obtained prior to the first dose.
Change From Baseline in Plasma Erythropoietin in Part 2 Participants at 4, 8, 12, and 24 Hours on Day 1
Baseline is defined as the last value obtained prior to the first dose.
Full Information
NCT ID
NCT00761657
First Posted
September 25, 2008
Last Updated
November 17, 2021
Sponsor
FibroGen
Collaborators
Astellas Pharma Inc
1. Study Identification
Unique Protocol Identification Number
NCT00761657
Brief Title
Phase 2 Study of Roxadustat in Participants With Anemia and Chronic Kidney Disease Not Requiring Dialysis
Official Title
A Randomized, Single-blind, Placebo-controlled, 4-Week Treatment Study of the Safety and Biologic Activity of Escalating Multiple Oral Doses of FG-4592 in Subjects With Chronic Kidney Disease Not Requiring Dialysis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
November 1, 2006 (Actual)
Primary Completion Date
June 21, 2010 (Actual)
Study Completion Date
June 21, 2010 (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 objective of the study is to evaluate the safety, tolerability, and pharmacodynamic effects of different oral doses of roxadustat administered 2 times a week (BIW) or 3 times a week (TIW) for up to 4 weeks to participants with chronic kidney disease (CKD) not requiring dialysis.
Detailed Description
This study in participants with CKD not requiring dialysis was conducted in 2 parts (designated Part 1 and Part 2). Part 1 evaluated roxadustat doses at 1.0 and 2.0 milligrams/kilograms (mg/kg). Part 2 evaluated roxadustat doses at 0.7, 1.5, and 2.0 mg/kg.
On 08 May 2007, the Food and Drug Administration (FDA) placed a clinical hold on the study until evaluation of a report of a death due to fulminant hepatic failure in a participant with CKD in a FibroGen-sponsored clinical trial of another hypoxia inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) (FG-2216) being investigated for treatment of anemia in participants with CKD and other diseases. The clinical hold resulted in early termination of Part 1 of the study. On 24 March 2008, the FDA lifted the clinical hold and Part 2 of this study started.
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, Stage 3 or 4 Chronic Kidney Disease, Renal, Anemia, Oral anemia treatment, Hemoglobin levels, Blood count, Erythropoietin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
117 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Roxadustat 0.7 mg/kg BIW
Arm Type
Experimental
Arm Description
Participants will receive roxadustat 0.7 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.
Arm Title
Roxadustat 0.7 mg/kg TIW
Arm Type
Experimental
Arm Description
Participants will receive roxadustat 0.7 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.
Arm Title
Roxadustat 1.0 mg/kg BIW
Arm Type
Experimental
Arm Description
Participants will receive roxadustat 1.0 mg/kg BIW orally with doses administered at least 72 hours apart for 29 days.
Arm Title
Roxadustat 1.0 mg/kg TIW
Arm Type
Experimental
Arm Description
Participants will receive roxadustat 1.0 mg/kg TIW orally with doses administered at least 48 hours apart for 26 days.
Arm Title
Roxadustat 1.5 mg/kg BIW
Arm Type
Experimental
Arm Description
Participants will receive roxadustat 1.5 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.
Arm Title
Roxadustat 1.5 mg/kg TIW
Arm Type
Experimental
Arm Description
Participants will receive roxadustat 1.5 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.
Arm Title
Roxadustat 2.0 mg/kg BIW
Arm Type
Experimental
Arm Description
Participants will receive roxadustat 2.0 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.
Arm Title
Roxadustat 2.0 mg/kg TIW
Arm Type
Experimental
Arm Description
Participants will receive roxadustat 2.0 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo orally, matching to the roxadustat dose, number of days per week, and duration.
Intervention Type
Drug
Intervention Name(s)
Roxadustat
Other Intervention Name(s)
FG-4592
Intervention Description
Capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Capsule
Primary Outcome Measure Information:
Title
Primary Safety Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Treatment Discontinuation (Parts 1 and 2 Combined)
Description
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 defined as an AE beginning after first dose of study drug until 28 days after last dose of study drug or existing AEs that worsened after first dose of study drug until the participant's last study visit. Severe AEs defined as incapacitating, inability to perform usual activities. Drug-related TEAEs defined as TEAEs with possible, probable, or definite relationship to study drug. Serious AE criteria included death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed here. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame
Baseline up to Week 16 (End of Study (EoS])
Title
Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Day 26-29 (End of Treatment)
Description
Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline was defined as the mean of last 3 available values prior to the first dose.
Time Frame
Baseline, End of Treatment (EoT) (Day 26 for TIW Dosing or Day 29 for BIW Dosing)
Title
Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Week 8 (2 Weeks of Follow Up)
Description
Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline is defined as the mean of last 3 available values prior to the first dose.
Time Frame
Baseline, Week 8 (2 Weeks of Follow Up)
Secondary Outcome Measure Information:
Title
Number of Participants With a Hemoglobin Response (Not Due to a RBC Transfusion or IV Iron Supplementation During Treatment)
Description
Hb response defined as an increase in Hb from baseline by ≥1.0 g/dL (not due to red blood cell transfusion or IV iron supplementation during treatment). The baseline for Hb was defined as the mean of the last 3 available Hb values obtained prior to the first dose.
Time Frame
Baseline up to Day 26-29 (EoT), up to Week 8 (2 weeks of follow up), and up to Week 16 (EoS, 4 weeks of follow up)
Title
Plasma Roxadustat Concentration (Part 2)
Time Frame
Predose on Days 3 (TIW dose groups) or 4 (BIW dose groups), 8, 15, 22, and 26 (TIW dose groups) or 29 (BIW dose groups)
Title
Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29
Description
Baseline is defined as the last value obtained prior to the first dose.
Time Frame
Baseline (Day 1), 1, 2, 3, 4, 6, 8, 12, 18, 24, 48, and 72 hours on Day 26 (TIW Dosing) or Day 29 (BIW Dosing)
Title
Change From Baseline in Plasma Erythropoietin in Part 2 Participants at 4, 8, 12, and 24 Hours on Day 1
Description
Baseline is defined as the last value obtained prior to the first dose.
Time Frame
Baseline, 4, 8, 12, and 24 hours on Day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 to 80 years of age. Participants aged over 75 years but otherwise meet all other participant selection criteria will be evaluated on a case-by-case basis and can be included in this study, per discretion of Sponsor's physician representative such as medical monitor or clinical leader.
Chronic Kidney Disease Stage 3 or 4 with hemoglobin <11.0 grams (g)/deciliter (dL).
Normal iron studies.
Normal folate and vitamin B12 levels.
Liver function tests within normal limits at screening.
Absence of active or chronic rectal bleeding.
Absence of diagnosis of age-related macular degeneration (AMD), diabetic macular edema, or diabetic proliferative retinopathy that is likely to require treatment during the trial.
Female participants must not be pregnant nor breastfeeding and agree to use acceptable method of contraception.
Male participants with partners who can have children must agree to use a medically acceptable method of contraception.
Exclusion Criteria:
Seropositive for HIV.
History of chronic liver disease.
History of polycystic kidney disease (PKD).
Uncontrolled hypertension (diastolic BP >110 millimeter of mercury (mmHg) or systolic BP >170 mmHg at screening).
New York Heart Association Class III or IV congestive heart failure.
Recent myocardial infarction or acute coronary syndrome.
History of myelodysplastic syndrome.
Any history of malignancy or a known genetic predisposition for developing cancer (for example, with diagnostic markers suggesting a genetic predisposition of cancer) except for curatively resected basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or resected benign colonic polyps.
Active inflammatory infection or chronic inflammatory disease.
Any clinically significant and uncontrolled medical condition considered a high risk for participation in an investigational study.
Blood clots within 4 weeks.
History of ongoing hemolysis or diagnosis of hemolytic syndrome.
Known history of bone marrow fibrosis.
History of hemosiderosis or hemochromatosis.
Androgen therapy within 12 weeks.
Red blood cell transfusion within 12 weeks.
Therapy with an erythropoiesis stimulating agent (ESA) such as human recombinant erythropoietin within the past 60 days.
Intravenous iron supplementation within the past 60 days.
Currently taking dapsone or acetaminophen >2.6 g/day.
History of prior organ transplantation.
Alcohol consumption greater than 3 or more drinks per day within the past year.
Use of an investigational medication or participation in an investigational study within 4 weeks preceding Day 1.
Positive urine toxicology screen for a substance that has not been prescribed for the participant.
Facility Information:
City
Peoria
State/Province
Arizona
ZIP/Postal Code
85381
Country
United States
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85284
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
City
Mission Viejo
State/Province
California
ZIP/Postal Code
92691
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
City
Arvada
State/Province
Colorado
ZIP/Postal Code
80002
Country
United States
City
Westminster
State/Province
Colorado
ZIP/Postal Code
80031
Country
United States
City
Middlebury
State/Province
Connecticut
ZIP/Postal Code
06762
Country
United States
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
City
Panama City
State/Province
Florida
ZIP/Postal Code
32401
Country
United States
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30901
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60616
Country
United States
City
Evergreen Park
State/Province
Illinois
ZIP/Postal Code
60805
Country
United States
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71101
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68510
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
City
Flushing
State/Province
New York
ZIP/Postal Code
11355
Country
United States
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
City
Wynnewood
State/Province
Pennsylvania
ZIP/Postal Code
19096
Country
United States
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77036
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
PubMed Identifier
26238121
Citation
Besarab A, Provenzano R, Hertel J, Zabaneh R, Klaus SJ, Lee T, Leong R, Hemmerich S, Yu KH, Neff TB. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. Nephrol Dial Transplant. 2015 Oct;30(10):1665-73. doi: 10.1093/ndt/gfv302. Epub 2015 Aug 3.
Results Reference
derived
Learn more about this trial
Phase 2 Study of Roxadustat in Participants With Anemia and Chronic Kidney Disease Not Requiring Dialysis
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