Clinical trial NCT02273726: Study to Evaluate the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Participants With ESRD on Stable Dialysis
Official title: A Phase 3, Open-Label, Randomized, Active-Controlled Study of the Efficacy and Safety of Roxadustat (FG-4592) in the Maintenance Treatment of Anemia in Subjects With End Stage Renal Disease (ESRD) on Stable Dialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: CKD Anemia in Stable Dialysis Patients
Keywords: Anemia
Chronic Kidney Disease
Dialysis
hemodialysis
peritoneal dialysis
hemoglobin
End stage renal disease
Stable Dialysis
erythropoietins
erythropoiesis stimulating agent
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Europe B.V.
name: AstraZeneca
First posted: 2014-10-24
Enrollment: 741
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy and safety of roxadustat compared with active control (epoetin alfa) for the maintenance treatment of anemia in participants with ESRD on dialysis.

Detailed description: This study will consist of three study periods as follows:

1. Screening Period of up to 6 weeks (8 weeks if on Mircera)
2. Treatment Period: a minimum of 52 weeks, a maximum of up to 3 years from the date last participant is randomized. Minimum study duration for participants enrolled under Protocol Amendment 1 or 2 may be less than 52 weeks
3. A Follow-up period of 4 weeks.

Participants will be randomized in a 1:1 ratio to receive either roxadustat or epoetin alfa (active control) in an open-label manner.

Eligibility criteria: Inclusion Criteria:

* Receiving dialysis for ESRD for ≥3 months. Incident dialysis participants (under Amendment 1 and 2) receiving dialysis for ESRD for ≥ 2 weeks but ≤ 4 months at the time of randomization
* Participants must be on ESA for ≥ 8 weeks prior to screening; incident dialysis participants must be on ESA for ≥ 4 weeks prior to screening.
* Mean of the 3 most recent central lab Hb values during the Screening Period must be ≥ 9.0 g/dL and ≤ 12.0 g/dL (for incident dialysis participants, mean of the 2 most recent Hb values must be ≥ 8.5 g/dL and ≤ 12.0 g/dL); with an absolute difference of ≤ 1.3 g/dL between the highest and the lowest value. Samples are obtained at least 4 days apart (2 days under Amendment 2) and the last Hb value must be within 10 days prior to the randomization visit
* Participants with ferritin level ≥ 100 nanograms (ng)/milliliter (mL) (\<100 ng/mL under Amendment 2) or transferrin saturation (TSAT) ≥ 20% (\<20% under Amendment 2) at screening may qualify upon receiving iron supplement (per local standard of care)
* Participants with a serum folate and Vitamin B12 ≥ lower limit of normal (LLN) (\< LLN under Amendment 2) at screening may qualify upon receiving supplement (per local standard of care)
* Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3x the upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5x ULN at screening
* Participant's body weight is 45 kilograms (kg) to 160 kg.

Exclusion Criteria:

* Participant has received an red blood cell (RBC) transfusion within 8 weeks (4 weeks under Amendment 2) prior to randomization
* Participant has known history of myelodysplastic syndrome or multiple myeloma
* Participant has known inherited disease such as thalassemia or sickle cell anemia or other known causes for anemia other than chronic kidney disease.
* Participant has known hemosiderosis, hemochromatosis, coagulation disorder,or hypercoagulable condition
* Participant has known chronic inflammatory disease that could cause anemia
* Participant has anticipated surgery that is expected to cause blood loss
* Participant has known gastrointestinal bleeding
* Participant has history of chronic liver disease (for example, chronic infectious hepatitis,chronic auto-immune liver disease,cirrhosis, or fibrosis of the liver)
* Participant with New York Heart Association (NYHA) Class III or IV congestive heart failure
* Participant has had a heart attack, stroke, seizure, or a thrombotic/thromboembolic event (for example, deep vein thrombosis or pulmonary embolism) within 12 weeks prior to participating in the study
* Participant has uncontrolled high blood pressure within 2 weeks prior to participating in the study
* Participant has a history of malignancy, except for the following: cancers determined to be cured or in remission for ≥2 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.)
* Participant is positive for human immunodeficiency virus (HIV), Hepatitis B surface antigen, or anti-hepatitis C virus antibody
* Participant with prior organ transplant who experience rejection within 6 months or on high doses of immunosuppressive therapy
* Participant has any of the following known untreated conditions; proliferative diabetic retinopathy, diabetic macular edema, macular degeneration or retinal vein occlusion.

Primary outcomes:
measure: US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Weeks 28 to 52), Regardless of Rescue Therapy
timeFrame: Baseline (Day 1, Week 0), Weeks 28 to 52
measure: Ex-U.S. Submission: Mean Hb Change From Baseline to the Average Weeks 28 to 36, Without Having Received Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period for Participants Enrolled Under the Original Protocol
timeFrame: Baseline (Day 1, Week 0), Weeks 28 to 36
Secondary outcomes:
measure: US (FDA Submission): Hb Responder Rate- Percentage of Participants With Mean Hb Level ≥10.0 g/dL Averaged Over Weeks 28 to 52, Regardless of Rescue Therapy
timeFrame: Weeks 28 to 52
measure: Ex-U.S. Submission: Hb Responder Rate- Percentage of Participants With Mean Hb 10.0 to 12.0 g/dL Averaged Over Weeks 28 to 36, Censoring for Rescue Therapy
timeFrame: Weeks 28 to 36
measure: Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28
timeFrame: Baseline (Day 1, Week 0), Weeks 12 to 28
measure: Change From Baseline in Hb Levels Averaged Over Weeks 18 to 24 Regardless of Rescue Therapy in Participants Whose Baseline High Sensitivity C-Reactive Protein (Hs-CRP)> Upper Limit of Normal (ULN)
timeFrame: Baseline (Day 1, Week 0), Weeks 18 to 24
measure: Average Monthly IV Iron Use Per Patient-Exposure-Month (PEM) During Weeks 28 to 52
timeFrame: Weeks 28 to 52
measure: Time to First RBC Transfusion
timeFrame: Baseline (Day 1, Week 0) up to last dose of study drug (maximum treatment duration was 183.7 weeks for roxadustat and 180.4 weeks for epoetin alfa)
measure: Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 20 to 28
timeFrame: Baseline (Day 1, Week 0), Weeks 20 to 28
measure: Time to First Exacerbation of Hypertension During Weeks 28 to 52
timeFrame: Weeks 28 to 52
measure: Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28
timeFrame: Baseline (Day 1, Week 0), Weeks 12 to 28
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Center
state: Arizona
city: Pine Bluff
country: United States
facility: Research Center
state: Arkansas
city: Chula Vista
country: United States
facility: Research Center
state: California
city: Chula Vista
country: United States
facility: Research Center
state: California
city: La Mesa
country: United States
facility: Research Center
state: California
city: Long Beach
country: United States
facility: Research Center
state: California
city: Long Beach
country: United States
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state: California
city: Los Angeles
country: United States
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state: California
city: Northridge
country: United States
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state: California
city: Ontario
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state: California
city: Roseville
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state: California
city: San Diego
country: United States
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state: California
city: San Dimas
country: United States
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state: California
city: San Gabriel
country: United States
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state: California
city: Whittier
country: United States
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state: California
city: Coral Springs
country: United States
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state: Florida
city: Lauderdale Lakes
country: United States
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state: Florida
city: Miami
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state: Florida
city: Miami
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state: Florida
city: Pembroke Pines
country: United States
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state: Florida
city: Tampa
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state: Florida
city: Albany
country: United States
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state: Georgia
city: Meridian
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state: Idaho
city: Shreveport
country: United States
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state: Louisiana
city: Springfield
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state: Massachusetts
city: Detroit
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state: Michigan
city: Detroit
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state: Michigan
city: Pontiac
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state: Michigan
city: Brookhaven
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state: Mississippi
city: Columbus
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state: Mississippi
city: Gulfport
country: United States
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state: Mississippi
city: Tupelo
country: United States
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state: Mississippi
city: Creve Coeur
country: United States
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state: Missouri
city: Kansas City
country: United States
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state: Missouri
city: Saint Ann
country: United States
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state: Missouri
city: Saint Louis
country: United States
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state: Missouri
city: Portsmouth
country: United States
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state: New Hampshire
city: North Brunswick
country: United States
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state: New Jersey
city: Albuquerque
country: United States
facility: Research Center
state: New Mexico
city: Gallup
country: United States
facility: Research Center
state: New Mexico
city: College Point
country: United States
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state: New York
city: New York
country: United States
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state: New York
city: Charlotte
country: United States
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state: North Carolina
city: Durham
country: United States
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state: North Carolina
city: Greenville
country: United States
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state: North Carolina
city: New Bern
country: United States
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state: North Carolina
city: Raleigh
country: United States
facility: Research Center
state: North Carolina
city: Rocky Mount
country: United States
facility: Research Center
state: North Carolina
city: Columbus
country: United States
facility: Research Center
state: Ohio
city: Columbus
country: United States
facility: Research Center
state: Ohio
city: Aiken
country: United States
facility: Research Center
state: South Carolina
city: Columbia
country: United States
facility: Research Center
state: South Carolina
city: Orangeburg
country: United States
facility: Research Center
state: South Carolina
city: Sumter
country: United States
facility: Research Center
state: South Carolina
city: Knoxville
country: United States
facility: Research Center
state: Tennessee
city: Knoxville
country: United States
facility: Research Center
state: Tennessee
city: Nashville
country: United States
facility: Research Center
state: Tennessee
city: Nashville
country: United States
facility: Research Center
state: Tennessee
city: Arlington
country: United States
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state: Texas
city: Edinburg
country: United States
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state: Texas
city: Fort Worth
country: United States
facility: Research Center
state: Texas
city: Fort Worth
country: United States
facility: Research Center
state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Grand Prairie
country: United States
facility: Research Center
state: Texas
city: Houston
country: United States
facility: Research Center
state: Texas
city: Houston
country: United States
facility: Research Center
state: Texas
city: Lubbock
country: United States
facility: Research Center
state: Texas
city: Mansfield
country: United States
facility: Research Center
state: Texas
city: San Antonio
country: United States
facility: Research Center
state: Texas
city: San Antonio
country: United States
facility: Research Center
state: Texas
city: Alexandria
country: United States
facility: Research Center
state: Virginia
city: Shorewood
country: United States
facility: Research Center
state: Wisconsin
city: Caguas
country: Puerto Rico
facility: Research Center
city: San Juan
country: Puerto Rico
facility: Research Center
Study officials:
affiliation: FibroGen
name: Meraf Eyassu
role: STUDY_DIRECTOR
References:
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.