Clinical trial NCT00761657: 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
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
First posted: 2008-09-29
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Chronic Kidney Disease Stage 3 or 4 with hemoglobin \<11.0 grams (g)/deciliter (dL).
3. Normal iron studies.
4. Normal folate and vitamin B12 levels.
5. Liver function tests within normal limits at screening.
6. Absence of active or chronic rectal bleeding.
7. 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.
8. Female participants must not be pregnant nor breastfeeding and agree to use acceptable method of contraception.
9. Male participants with partners who can have children must agree to use a medically acceptable method of contraception.

Exclusion Criteria:

1. Seropositive for HIV.
2. History of chronic liver disease.
3. History of polycystic kidney disease (PKD).
4. Uncontrolled hypertension (diastolic BP \>110 millimeter of mercury (mmHg) or systolic BP \>170 mmHg at screening).
5. New York Heart Association Class III or IV congestive heart failure.
6. Recent myocardial infarction or acute coronary syndrome.
7. History of myelodysplastic syndrome.
8. 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.
9. Active inflammatory infection or chronic inflammatory disease.
10. Any clinically significant and uncontrolled medical condition considered a high risk for participation in an investigational study.
11. Blood clots within 4 weeks.
12. History of ongoing hemolysis or diagnosis of hemolytic syndrome.
13. Known history of bone marrow fibrosis.
14. History of hemosiderosis or hemochromatosis.
15. Androgen therapy within 12 weeks.
16. Red blood cell transfusion within 12 weeks.
17. Therapy with an erythropoiesis stimulating agent (ESA) such as human recombinant erythropoietin within the past 60 days.
18. Intravenous iron supplementation within the past 60 days.
19. Currently taking dapsone or acetaminophen \>2.6 g/day.
20. History of prior organ transplantation.
21. Alcohol consumption greater than 3 or more drinks per day within the past year.
22. Use of an investigational medication or participation in an investigational study within 4 weeks preceding Day 1.
23. Positive urine toxicology screen for a substance that has not been prescribed for the participant.

Primary outcomes:
measure: 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)
timeFrame: Baseline up to Week 16 (End of Study (EoS])
measure: Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Day 26-29 (End of Treatment)
timeFrame: Baseline, End of Treatment (EoT) (Day 26 for TIW Dosing or Day 29 for BIW Dosing)
measure: Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Week 8 (2 Weeks of Follow Up)
timeFrame: Baseline, Week 8 (2 Weeks of Follow Up)
Secondary outcomes:
measure: Number of Participants With a Hemoglobin Response (Not Due to a RBC Transfusion or IV Iron Supplementation During Treatment)
timeFrame: 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)
measure: Plasma Roxadustat Concentration (Part 2)
timeFrame: 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)
measure: Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29
timeFrame: 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)
measure: Change From Baseline in Plasma Erythropoietin in Part 2 Participants at 4, 8, 12, and 24 Hours on Day 1
timeFrame: Baseline, 4, 8, 12, and 24 hours on Day 1
Other outcomes:
Locations:
city: Peoria
country: United States
state: Arizona
city: Tempe
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Mission Viejo
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Whittier
country: United States
state: California
city: Arvada
country: United States
state: Colorado
city: Westminster
country: United States
state: Colorado
city: Middlebury
country: United States
state: Connecticut
city: Ocala
country: United States
state: Florida
city: Panama City
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Evergreen Park
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Detroit
country: United States
state: Michigan
city: Lincoln
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Flushing
country: United States
state: New York
city: Winston-Salem
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Medford
country: United States
state: Oregon
city: Wynnewood
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Orangeburg
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
Study officials:
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.
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.