Study to Evaluate the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Participants With ESRD on Stable Dialysis

NCT02273726 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: FGCL-4592-064
• Study Type: interventional
• Target: 741
• Locations: 2 countries
• Sites: 76

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.

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

Outcome Measures

Primary Outcomes (2)

• US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Weeks 28 to 52), Regardless of Rescue Therapy

  Hb values under the influence of rescue therapy were not censored in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or red blood cell (RBC) transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment. The intermittent missing Hb data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model, Monotone missing data were imputed by regression from its own treatment group.

  Baseline (Day 1, Week 0), Weeks 28 to 52

• 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

  Hb values under the influence of rescue therapy were censored up to 6 weeks in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment.

  Baseline (Day 1, Week 0), Weeks 28 to 36

Secondary Outcomes (9)

• 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

  Weeks 28 to 52

• 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

  Weeks 28 to 36

• Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28

  Baseline (Day 1, Week 0), Weeks 12 to 28

• 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)

  Baseline (Day 1, Week 0), Weeks 18 to 24

• Average Monthly IV Iron Use Per Patient-Exposure-Month (PEM) During Weeks 28 to 52

  Weeks 28 to 52

Study Arms (2)

Roxadustat

EXPERIMENTAL

Participants will receive roxadustat tablets, administered orally 3 times weekly (TIW). Initial roxadustat dose will be based on the participant's average prescribed erythropoietin stimulating agent (ESA) dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments will be permitted to maintain a hemoglobin (Hb) level of approximately 11 grams (g)/deciliter (dL). The maximum roxadustat dose is 3.0 milligrams (mg)/kilogram (kg) per dose or 400 mg per administration (whichever is lower).

Drug: Roxadustat

Epoetin Alfa

ACTIVE COMPARATOR

Participants on hemodialysis (HD) will receive epoetin alfa, administered intravenously (IV) TIW and participants on home HD or peritoneal dialysis (PD) will receive epoetin alfa, administered subcutaneously (SC). Initial epoetin alfa dose will be based on the participant's average weekly prescribed ESA dose in 4 weeks prior to randomization if on epoetin or darbepoetin, and average monthly (4-week) prescribed ESA dose in 8 weeks prior to randomization if on Mircera®. In case of a change in route of administration from SC to IV (TIW), the initial dose of IV epoetin alfa will be determined by the investigator per local standard of care (SOC). Dose adjustments will follow the recommendations as per the approved country-specific product label (United States Package Insert \[USPI\] or Summary of Product Characteristics \[SmPC\]) or local SOC.

Drug: Epoetin Alfa

Interventions

Epoetin Alfa DRUG

Epoetin alfa will be administered per dose and schedule specified in the arm.

Epoetin Alfa

Roxadustat DRUG

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

Also known as: FG-4592

Roxadustat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kyntra Bio: lead
• Astellas Pharma Europe B.V.: collaborator
• AstraZeneca: collaborator

Study Sites (76)

Research Center

Phoenix, Arizona, 85012, United States

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Pine Bluff, Arkansas, 71603, United States

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Chula Vista, California, 91910, United States

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Chula Vista, California, 91915, United States

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La Mesa, California, 91942, United States

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Long Beach, California, 90806, United States

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Long Beach, California, 90813, United States

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Los Angeles, California, 90057, United States

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Northridge, California, 91324, United States

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Ontario, California, 91762, United States

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Roseville, California, 95661, United States

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San Diego, California, 92111, United States

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San Dimas, California, 91773, United States

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San Gabriel, California, 91776, United States

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Whittier, California, 90603, United States

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Coral Springs, Florida, 33071, United States

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Lauderdale Lakes, Florida, 33313, United States

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Miami, Florida, 33143, United States

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Miami, Florida, 33173, United States

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Pembroke Pines, Florida, 33028, United States

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Tampa, Florida, 33614, United States

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Albany, Georgia, 31701, United States

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Meridian, Idaho, 83642, United States

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Shreveport, Louisiana, 71101, United States

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Springfield, Massachusetts, 01107, United States

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Detroit, Michigan, 48202, United States

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Detroit, Michigan, 48236, United States

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Pontiac, Michigan, 48341, United States

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Brookhaven, Mississippi, 39601, United States

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Columbus, Mississippi, 39705, United States

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Gulfport, Mississippi, 39501, United States

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Tupelo, Mississippi, 38801, United States

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Creve Coeur, Missouri, 63141, United States

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Kansas City, Missouri, 64131, United States

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Saint Ann, Missouri, 63074, United States

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St Louis, Missouri, 63110, United States

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Portsmouth, New Hampshire, 03885, United States

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North Brunswick, New Jersey, 08902, United States

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Albuquerque, New Mexico, 87109, United States

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Gallup, New Mexico, 87301, United States

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College Point, New York, 11356, United States

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New York, New York, 11355, United States

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Charlotte, North Carolina, 28204, United States

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Durham, North Carolina, 27704, United States

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Greenville, North Carolina, 27834, United States

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New Bern, North Carolina, 28562, United States

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Raleigh, North Carolina, 27609, United States

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Rocky Mount, North Carolina, 27804, United States

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Columbus, Ohio, 43210, United States

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Columbus, Ohio, 43215, United States

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Aiken, South Carolina, 29803, United States

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Columbia, South Carolina, 29203, United States

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Orangeburg, South Carolina, 29118, United States

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Sumter, South Carolina, 29150, United States

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Knoxville, Tennessee, 37923, United States

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Knoxville, Tennessee, 37924, United States

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Nashville, Tennessee, 37205, United States

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Nashville, Tennessee, 37232, United States

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Arlington, Texas, 76015-2368, United States

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Edinburg, Texas, 78539, United States

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Fort Worth, Texas, 76104, United States

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Fort Worth, Texas, 76105, United States

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Fort Worth, Texas, 76112, United States

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Fort Worth, Texas, 76133, United States

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Fort Worth, Texas, 76164, United States

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Grand Prairie, Texas, 75050, United States

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Houston, Texas, 77054, United States

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Houston, Texas, 77099, United States

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Lubbock, Texas, 79430, United States

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Mansfield, Texas, 76063, United States

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San Antonio, Texas, 78202, United States

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San Antonio, Texas, 78221, United States

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Alexandria, Virginia, 20735, United States

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Shorewood, Wisconsin, 53226, United States

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Caguas, 00725, Puerto Rico

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San Juan, 00926, Puerto Rico

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Related Publications (3)

• Hamano T, Yamaguchi Y, Goto K, Martin S, Jiletcovici A, Dellanna F, Akizawa T, Barratt J. Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Four Global Roxadustat Phase 3 Trials. Adv Ther. 2024 Apr;41(4):1553-1575. doi: 10.1007/s12325-023-02728-2. Epub 2024 Feb 16.

  PMID: 38363466 DERIVED

• Barratt J, Dellanna F, Portoles J, Choukroun G, De Nicola L, Young J, Dimkovic N, Reusch M. Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies. Adv Ther. 2023 Apr;40(4):1546-1559. doi: 10.1007/s12325-023-02433-0. Epub 2023 Feb 7.

  PMID: 36749544 DERIVED

• 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.

  PMID: 36005278 DERIVED

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic; Kidney Failure, Chronic

Interventions

Epoetin Alfa; roxadustat

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: FibroGen, Inc.

064study@fibrogen.com

415-978-1441

Study Officials

• Meraf Eyassu

  Kyntra Bio

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: October 24, 2014
• Study Start: January 15, 2015
• Primary Completion: September 19, 2018
• Study Completion: September 19, 2018
• Last Updated: October 29, 2021
• Results First Posted: October 29, 2021

Record last verified: 2021-09

Locations

US (74); PR (2)