Phase 2 Study of Roxadustat in Participants With Anemia and Chronic Kidney Disease Not Requiring Dialysis

NCT00761657 | Completed Phase 2 Results DMC

• 1 other identifier: FGCL-SM4592-017
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 34

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline up to Week 16 (End of Study (EoS])

• 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.

  Baseline, End of Treatment (EoT) (Day 26 for TIW Dosing or Day 29 for BIW Dosing)

• 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.

  Baseline, Week 8 (2 Weeks of Follow Up)

Secondary Outcomes (4)

• Number of Participants With a Hemoglobin Response (Not Due to a RBC Transfusion or IV Iron Supplementation During Treatment)

  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)

• Plasma Roxadustat Concentration (Part 2)

  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)

• Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29

  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)

• Change From Baseline in Plasma Erythropoietin in Part 2 Participants at 4, 8, 12, and 24 Hours on Day 1

  Baseline, 4, 8, 12, and 24 hours on Day 1

Study Arms (9)

Roxadustat 0.7 mg/kg BIW

EXPERIMENTAL

Participants will receive roxadustat 0.7 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.

Drug: Roxadustat

Roxadustat 0.7 mg/kg TIW

EXPERIMENTAL

Participants will receive roxadustat 0.7 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.

Drug: Roxadustat

Roxadustat 1.0 mg/kg BIW

EXPERIMENTAL

Participants will receive roxadustat 1.0 mg/kg BIW orally with doses administered at least 72 hours apart for 29 days.

Drug: Roxadustat

Roxadustat 1.0 mg/kg TIW

EXPERIMENTAL

Participants will receive roxadustat 1.0 mg/kg TIW orally with doses administered at least 48 hours apart for 26 days.

Drug: Roxadustat

Roxadustat 1.5 mg/kg BIW

EXPERIMENTAL

Participants will receive roxadustat 1.5 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.

Drug: Roxadustat

Roxadustat 1.5 mg/kg TIW

EXPERIMENTAL

Participants will receive roxadustat 1.5 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.

Drug: Roxadustat

Roxadustat 2.0 mg/kg BIW

EXPERIMENTAL

Participants will receive roxadustat 2.0 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.

Drug: Roxadustat

Roxadustat 2.0 mg/kg TIW

EXPERIMENTAL

Participants will receive roxadustat 2.0 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.

Drug: Roxadustat

Placebo

PLACEBO COMPARATOR

Participants will receive placebo orally, matching to the roxadustat dose, number of days per week, and duration.

Drug: Placebo

Interventions

Roxadustat DRUG

Capsule

Also known as: FG-4592

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 DRUG

Capsule

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kyntra Bio: lead
• Astellas Pharma Inc: collaborator

Study Sites (34)

Unknown Facility

Peoria, Arizona, 85381, United States

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Tempe, Arizona, 85284, United States

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Los Angeles, California, 90095, United States

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Mission Viejo, California, 92691, United States

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Sacramento, California, 95825, United States

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San Diego, California, 92123, United States

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Whittier, California, 90603, United States

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Arvada, Colorado, 80002, United States

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Westminster, Colorado, 80031, United States

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Middlebury, Connecticut, 06762, United States

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Ocala, Florida, 34471, United States

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Panama City, Florida, 32401, 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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Augusta, Georgia, 30901, United States

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Chicago, Illinois, 60616, United States

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Evergreen Park, Illinois, 60805, United States

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Wichita, Kansas, 67214, United States

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Louisville, Kentucky, 40202, United States

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Baton Rouge, Louisiana, 70809, United States

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Shreveport, Louisiana, 71101, United States

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Detroit, Michigan, 48236, United States

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Lincoln, Nebraska, 68510, United States

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Las Vegas, Nevada, 89106, United States

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Flushing, New York, 11355, United States

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Winston-Salem, North Carolina, 27103, United States

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Cleveland, Ohio, 44109, United States

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Toledo, Ohio, 43606, United States

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Medford, Oregon, 97504, United States

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Wynnewood, Pennsylvania, 19096, 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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Chattanooga, Tennessee, 37404, United States

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Houston, Texas, 77036, United States

Location

Related Publications (2)

• 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

• 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.

  PMID: 26238121 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Anemia

Interventions

roxadustat

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

Results Point of Contact

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

415-978-1441

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 25, 2008
• First Posted: September 29, 2008
• Study Start: November 1, 2006
• Primary Completion: June 21, 2010
• Study Completion: June 21, 2010
• Last Updated: November 19, 2021
• Results First Posted: November 19, 2021

Record last verified: 2021-11

Locations

US (34)