Study of Roxadustat (FG-4592) in Participants With End-Stage Renal Disease Receiving Maintenance Hemodialysis

NCT01147666 | Completed Phase 2 Results DMC

• 1 other identifier: FGCL-4592-040
• Study Type: interventional
• Target: 161
• Locations: 1 country
• Sites: 25

Brief Summary

The primary objective of this study is to evaluate the efficacy and safety of roxadustat in participants with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) therapy, previously treated with intravenous (IV) epoetin alfa.

Conditions

End Stage Renal Disease; Anemia

Keywords

Kidney; End Stage Renal Disease; ESRD; Chronic Kidney Disease; CKD; Renal; Anemia; Oral anemia treatment; Hemoglobin levels; Blood count; Erythropoietin; Hemodialysis; Normoresponder; Hyporesponder

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only

  Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. Last observation carried forward (LOCF) method was used to impute missing values.

  Week 7

• Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks

  Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

  Week 7

• Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks

  The average of the mean Hb values that were above 11 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

  Weeks 17, 18, 19, and 20

Secondary Outcomes (16)

• Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)

  Weeks 17, 18, 19, and 20

• Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)

  Weeks 17, 18, 19, and 20

• Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks

  Baseline, Week 7

• Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks

  Baseline, Weeks 8, 10, 12, 14, 17, 19, and 20

• Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only

  Baseline up to Week 6

Study Arms (15)

Cohort A-1 (Roxadustat 1.0 mg/kg TIW)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.0 milligrams (mg)/kg, administered orally 3 times weekly (TIW) in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 grams \[g\]/deciliter \[dL\]) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-2 (Roxadustat 1.5 mg/kg TIW)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-3 (Roxadustat 2.0 mg/kg TIW)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-4 (Roxadustat 1.8 mg/kg TIW)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who have not completed 6-week treatment at the time of Amendment 2, will continue treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-5 (Roxadustat 1.8 mg/kg TIW)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-6 (Roxadustat 1.3 mg/kg TIW)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (\>60 to 90 kg), and heavy weight (\>90 to 140 kg) participants will receive roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (\>60 to 90 kg), and heavy weight (\>90 to 140 kg) participants will receive roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-9 (Roxadustat 2.0 mg/kg)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)

EXPERIMENTAL

Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (\>60 to 90 kg), and heavy weight (\>90 to 140 kg) participants will receive roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohorts A (Epoetin Alfa)

ACTIVE COMPARATOR

Normoresponsive participants will receive IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing will occur on dialysis days in each Cohort A. Dose adjustment will be per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.

Drug: Epoetin Alfa

Cohort B-1 (Roxadustat 1.5 mg/kg TIW)

EXPERIMENTAL

Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort B-2 (Roxadustat 2.0 mg/kg TIW)

EXPERIMENTAL

Hyporesponsive participants (with baseline epoetin alfa dosage \>115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who have not completed 6-week treatment at the time of Amendment 2, will continue treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.

Drug: Roxadustat

Cohort B (Epoetin Alfa)

ACTIVE COMPARATOR

Hyporesponsive participants will receive IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing will occur on dialysis days in each Cohort B. Dose adjustment will be per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.

Drug: Epoetin Alfa

Cohort B (Placebo)

PLACEBO COMPARATOR

Hyporesponsive participants will receive placebo matched to roxadustat, administered orally TIW for 19 weeks.

Other: Placebo

Interventions

Roxadustat DRUG

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

Also known as: FG-4592

Cohort A-1 (Roxadustat 1.0 mg/kg TIW); Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg); Cohort A-2 (Roxadustat 1.5 mg/kg TIW); Cohort A-3 (Roxadustat 2.0 mg/kg TIW); Cohort A-4 (Roxadustat 1.8 mg/kg TIW); Cohort A-5 (Roxadustat 1.8 mg/kg TIW); Cohort A-6 (Roxadustat 1.3 mg/kg TIW); Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg); Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg); Cohort A-9 (Roxadustat 2.0 mg/kg); Cohort B-1 (Roxadustat 1.5 mg/kg TIW); Cohort B-2 (Roxadustat 2.0 mg/kg TIW)

Epoetin Alfa DRUG

Epoetin Alfa will be administered per dose and schedule specified in the arms.

Cohort B (Epoetin Alfa); Cohorts A (Epoetin Alfa)

Placebo OTHER

Placebo matching to roxadustat will be administered per schedule specified in the arm.

Cohort B (Placebo)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ESRD and receiving maintenance HD TIW for ≥4 months prior to Day 1
• Two most recent Hb values obtained during screening period must be within the ranges set below:
• i) Group A. Normoresponder Criteria: Hb range in the 8 weeks prior to randomization within 9.0 to 13.5 g/dL ii) Group B. Hyporesponder Criteria: Hb range in the 8 weeks prior to randomization within 8.5 to 13.5 g/dL
• Epoetin alfa, dose requirements:
• i) Group A. Normoresponder Criteria - Cohorts A-1 to A-12: Stable IV epoetin alfa dose at baseline (that is, no more than a 30% fluctuation in the weekly dose) during the 4 weeks prior to study Day -3
• Cohorts A-1 to A-4: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 85 IU/kg/dose, TIW; weekly dose between 75 and 255 IU/kg/week
• Cohort A-5: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to 115 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week
• Cohort A-9: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to 150 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week
• Cohorts A-6 to A-8: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 115 IU/kg/dose, TIW, and two times a week (BIW); total weekly dose between 75 and 345 IU/kg/week
• Cohorts A-10 to A-12: Optional cohorts to be decided (TBD), dosing frequency and dose range to be determined by sponsor ii) Group B. Hyporesponder Criteria:
• <!-- -->
• Cohort B-1 (completed): Current and previous (past 4 weeks) epoetin alfa dose range 125 to 400 IU/kg/dose, TIW; weekly dose between 375 and 1200 IU/kg/week
• Cohort B-2 to B-4: Current and previous (past 4 weeks) epoetin alfa dose range \>115 IU/kg/dose, TIW; total weekly dose \>345 IU/kg/week no requirement for stability of epoetin alfa doses
• Complete Blood Count (CBC), Hematology, liver function blood tests, serum folate and vitamin B12 within acceptable limits
• Absence of active or chronic gastrointestinal bleeding

You may not qualify if:

• Anticipated change in HD prescription
• 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
• 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
• History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric
• Active hemolysis or diagnosis of hemolytic syndrome
• Known bone marrow fibrosis
• Uncontrolled or symptomatic secondary hyperparathyroidism
• Any prior organ transplantation
• Drug-treated gastroparesis or short-bowel syndrome
• History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the participant
• Prior treatment with roxadustat

Sponsors & Collaborators

• Kyntra Bio: lead
• AstraZeneca: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (25)

Unknown Facility

Tempe, Arizona, United States

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Pine Bluff, Arkansas, United States

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Azusa, California, United States

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Los Angeles, California, United States

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Northridge, California, United States

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Ontario, California, United States

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Paramount, California, United States

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Yuba City, California, United States

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Miami, Florida, United States

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Pembroke Pines, Florida, United States

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Honolulu, Hawaii, United States

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Louisville, Kentucky, United States

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Detroit, Michigan, United States

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Kansas City, Missouri, United States

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Paterson, New Jersey, United States

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New York, New York, United States

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Rosedale, New York, United States

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Williamsville, New York, United States

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Toledo, Ohio, United States

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Orangeburg, South Carolina, United States

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Arlington, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Fairfax, Virginia, United States

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Related Publications (1)

• 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

Kidney Failure, Chronic; Anemia; Renal Insufficiency, Chronic

Interventions

roxadustat; Epoetin Alfa

Condition Hierarchy (Ancestors)

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; Hematologic Diseases; Hemic and Lymphatic Diseases

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.

415-978-1441

Study Officials

• Marietta Franco

  Kyntra Bio

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2010
• First Posted: June 22, 2010
• Study Start: May 17, 2010
• Primary Completion: October 15, 2012
• Study Completion: October 15, 2012
• Last Updated: January 11, 2022
• Results First Posted: January 11, 2022

Record last verified: 2021-12

Locations

US (25)