Clinical trial NCT01750190: A Study of Roxadustat for the Treatment of Anemia in Participants With Chronic Kidney Disease and Not Receiving Dialysis
Official title: A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat (FG-4592) for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: CKD Anemia
Keywords: anemia
chronic kidney disease (CKD)
non-dialysis
Hemoglobin (Hb)
End-Stage Renal Disease
erythropoeitin
ASP1517
erythropoeisis stimulating-agent
AZD9941
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Europe B.V.
name: AstraZeneca
First posted: 2012-12-17
Enrollment: 922
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 purpose of this study is to determine whether roxadustat is safe and effective in the treatment of anemia in participants with chronic kidney disease and not on dialysis.

Detailed description: There is a screening period of up to 6 weeks, a variable treatment period for individual participants. In order to complete the treatment period simultaneously for all study participants, the minimum treatment duration may be less than 52 weeks, with a maximum treatment duration of up to 3 years after the last participant is randomized, and a post-treatment follow-up period of 4 weeks. Participants who prematurely discontinued from treatment will be expected to complete the Early Termination (ET) and End of Study (EOS) visits. Such participants will be considered non-completers, but they will be expected to participate in long-term follow-up (LTFU) for cardiovascular events (CV) of interest, vital status, and hospitalizations until overall study closure unless the participant withdrew consent for this LTFU data collection. Participants were randomized in a 2:1 ratio to receive either roxadustat or placebo in a double-blind manner.

Eligibility criteria: Inclusion Criteria:

* Chronic kidney disease Stages 3, 4, or 5 and not receiving dialysis
* Anemia qualified by measurements of hemoglobin values during screening
* Additional blood work must be in a safe range for study entry
* Body weight 45 to 160 kilograms (kg)
* Willingness to use contraception if of child-bearing potential

Exclusion Criteria:

* Treatment with an erythropoiesis-stimulating agent (ESA) within 12 weeks prior to study participation
* More than 1 dose of intravenous iron within 12 weeks prior to study participation
* Blood transfusion within 8 weeks prior to study participation
* Active infection
* Chronic liver disease
* Severe congestive heart failure, recent heart attack, stroke, seizure, or blood clot
* Uncontrolled blood pressure within 2 weeks prior to study participation
* Renal cell carcinoma
* History of malignancy, including multiple myeloma or other myelodysplastic syndrome
* Chronic inflammatory disease that could impact red blood cell production
* Any prior organ transplant or a scheduled organ transplantation
* Anticipated elective surgery that is expected to lead to significant blood loss or anticipated elective heart procedure
* Gastrointestinal bleeding
* Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
* Recent use of an investigational drug or treatment, or participation in an investigational study

Primary outcomes:
measure: United States (US FDA) Submission: Mean Change From Baseline in Hb (g/dL) Over Weeks 28 to 52 Regardless of Rescue Therapy
timeFrame: Baseline (Day 1, Week 0), Weeks 28 to 52
measure: Ex-US Submission: Number (%) of Participants Who Achieved a Hb Response During the First 24-Weeks of Treatment Censoring for Rescue Therapy
timeFrame: Baseline up to Week 24
Secondary outcomes:
measure: Mean Change From Baseline in Hb Averaged Over Weeks 28 to 36 With Censoring for Rescue Therapy
timeFrame: Baseline (Day 1, Week 0), Weeks 28 to 36
measure: Mean Change From Baseline in Hb Averaged Over Weeks 28 to 52 Regardless of Rescue Therapy in Participants With Baseline C-Reactive Protein (CRP) >Upper Limit of Normal (ULN)
timeFrame: Baseline (Day 1, Week 0), Weeks 28 to 52
measure: Number (%) of Participants With Hb ≥10 g/dL Averaged Over Weeks 28 to 36 With Censoring for Rescue Therapy
timeFrame: Weeks 28 to 36
measure: Mean 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: Rate of Change in eGFR From Baseline up to 12 Months (Linear Random Coefficient Model With Observed Data)
timeFrame: Baseline, Month 12
measure: Number of Participants Who Received Blood/RBC Transfusion in the First 52 Weeks of Treatment
timeFrame: Baseline up to Week 52
measure: Number (%) of Participants Who Received Rescue Therapy in the First 24 Weeks and in the First 52 Weeks of Treatment
timeFrame: Baseline (Day 1, Week 0) up to Week 24 and up to Week 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
measure: Number (%) of Participants Who Experienced Exacerbation of Hypertension
timeFrame: Baseline up to Week 52
measure: Mean Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 20 to 28
timeFrame: Baseline, Weeks 20 to 28
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Investigational Site
state: Alabama
city: Tempe
country: United States
facility: Investigational Site
state: Arizona
city: Alhambra
country: United States
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state: California
city: Chula Vista
country: United States
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state: California
city: Inglewood
country: United States
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state: California
city: La Mesa
country: United States
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state: California
city: La Palma
country: United States
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state: California
city: Lynwood
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state: California
city: Northridge
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state: California
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city: Riverside
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city: Roseville
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city: San Dimas
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city: Whittier
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city: Coral Gables
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state: Florida
city: Cutler Bay
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city: Hialeah
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city: Miami
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city: Miami
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city: Miami
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city: Pembroke Pines
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city: Winter Park
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state: Florida
city: Augusta
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state: Georgia
city: Caldwell
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state: Idaho
city: Shreveport
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state: Louisiana
city: Baltimore
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state: Maryland
city: Boston
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state: Massachusetts
city: Detroit
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state: Michigan
city: Flint
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city: Flint
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state: Michigan
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state: Missouri
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city: Raleigh
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city: Morgantown
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state: West Virginia
city: Ciudad Evita
country: Argentina
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state: Buenos Aires
city: Moron
country: Argentina
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state: Buenos Aires
city: González Catán
country: Argentina
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state: Provincia De Buenos Aires
city: Junin
country: Argentina
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state: Provincia De Buenos Aires
city: Pergamino
country: Argentina
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state: Provincia De Buenos Aires
city: Villa Domínico
country: Argentina
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state: Provincia De Buenos Aires
city: Ciudad de Cordoba
country: Argentina
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state: Provincia De Cordoba
city: Buenos Aires
country: Argentina
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country: Argentina
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city: Santa Fe
country: Argentina
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city: Liverpool
country: Australia
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state: New South Wales
city: Gosford
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city: Launceston
country: Australia
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city: Melbourne
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city: New Lambton Heights
country: Australia
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city: Randwick
country: Australia
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city: Temuco
country: Chile
facility: Investigational Site
state: Region De La Araucania
city: Santiago
country: Chile
facility: Investigational Site
state: Region Metropolitana
city: Barranquilla
country: Colombia
facility: Investigational Site
state: Atlantico
city: Bogota
country: Colombia
facility: Investigational Site
state: Cundinamarca
city: Hong Kong
country: Hong Kong
facility: Investigational Site
state: Pokfulam
city: Chai Wan
country: Hong Kong
facility: Investigational Site
city: Shatin
country: Hong Kong
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city: Tai Po
country: Hong Kong
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city: Anyang-Si
country: Korea, Republic of
facility: Investigational Site
state: Gyeonggi-Do
city: Goyang-Si
country: Korea, Republic of
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state: Gyeonggi-Do
city: Guri-Si
country: Korea, Republic of
facility: Investigational Site
state: Gyeonggi-Do
city: Seongnam-Si
country: Korea, Republic of
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state: Gyeonggi-Do
city: Busan
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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city: Alor Setar
country: Malaysia
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city: Kajang
country: Malaysia
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city: Kuala Lumpur
country: Malaysia
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city: Kuala Lumpur
country: Malaysia
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city: Kuching
country: Malaysia
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city: Pulau Pinang
country: Malaysia
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city: Sungai Petani
country: Malaysia
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city: Taiping
country: Malaysia
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city: Mexico City
country: Mexico
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state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Investigational Site
state: Jalisco
city: Monterrey
country: Mexico
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state: Nuevo Leon
city: Merida
country: Mexico
facility: Investigational Site
state: Yucatan
city: Aguascalientes
country: Mexico
facility: Investigational Site
city: San Luis Potosi
country: Mexico
facility: Investigational Site
city: Auckland
country: New Zealand
facility: Investigational Site
city: Hamilton
country: New Zealand
facility: Investigational Site
city: Tauranga
country: New Zealand
facility: Investigational Site
city: Bellavista
country: Peru
facility: Investigational Site
state: Callao
city: San Martin de Porres
country: Peru
facility: Investigational Site
state: Lima
city: Lima
country: Peru
facility: Investigational site
city: Lima
country: Peru
facility: Investigational Site
city: Dasmarinas
country: Philippines
facility: Investigational Site
state: Cavite
city: Davao City
country: Philippines
facility: Investigational Site
state: Davao
city: Pasig
country: Philippines
facility: Investigational site
city: Quezon City
country: Philippines
facility: Investigational Site
city: Quezon City
country: Philippines
facility: Investigational Site
city: Ponce
country: Puerto Rico
facility: Investigational Site
city: San Juan
country: Puerto Rico
facility: Investigational Site
city: Singapore
country: Singapore
facility: Investigational Site
city: Singapore
country: Singapore
facility: Investigational Site
city: Singapore
country: Singapore
facility: Investigational Site
city: Changhua
country: Taiwan
facility: Investigational Site
city: Hualien City
country: Taiwan
facility: Investigational Site
city: Kaohsiung
country: Taiwan
facility: Investigational Site
city: Kaohsiung
country: Taiwan
facility: Investigational Site
city: Kaohsiung
country: Taiwan
facility: Investigational Site
city: Taichung
country: Taiwan
facility: Investigational Site
city: Taichung
country: Taiwan
facility: Investigational Site
city: Tainan City
country: Taiwan
facility: Investigational Site
city: Tainan
country: Taiwan
facility: Investigational Site
city: Taipei
country: Taiwan
facility: Investigational Site
city: Taipei
country: Taiwan
facility: Investigational Site
city: Taipei
country: Taiwan
facility: Investigational Site
city: Bangkok
country: Thailand
facility: Investigational Site
city: Bangkok
country: Thailand
facility: Investigational Site
city: Chiang Mai
country: Thailand
facility: Investigational Site
Study officials:
affiliation: FibroGen
name: Mark Eisner, MD, MPH
role: STUDY_CHAIR
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: Provenzano R, Szczech L, Leong R, Saikali KG, Zhong M, Lee TT, Little DJ, Houser MT, Frison L, Houghton J, Neff TB. Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD: Pooled Results of Three Randomized Clinical Trials. Clin J Am Soc Nephrol. 2021 Aug;16(8):1190-1200. doi: 10.2215/CJN.16191020.
citation: Coyne DW, Roger SD, Shin SK, Kim SG, Cadena AA, Moustafa MA, Chan TM, Besarab A, Chou W, Bradley C, Eyassu M, Leong R, Lee TT, Saikali KG, Szczech L, Yu KP. Roxadustat for CKD-related Anemia in Non-dialysis Patients. Kidney Int Rep. 2020 Dec 5;6(3):624-635. doi: 10.1016/j.ekir.2020.11.034. eCollection 2021 Mar.