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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01750190




Registration number
NCT01750190
Ethics application status
Date submitted
11/12/2012
Date registered
17/12/2012
Date last updated
1/10/2021

Titles & IDs
Public title
A Study of Roxadustat for the Treatment of Anemia in Participants With Chronic Kidney Disease and Not Receiving Dialysis
Scientific 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
Secondary ID [1] 0 0
FGCL-4592-060
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
CKD Anemia 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Blood 0 0 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Roxadustat
Treatment: Drugs - Placebo

Experimental: Roxadustat - Participants will receive roxadustat tablets orally 3 times a week (TIW). The initial dose will be according to the tiered weight-based approach, with starting roxadustat doses of 70 milligrams (mg) TIW to participants weighing \<70 kilograms (kg) and roxadustat doses of 100 mg TIW to participants weighing =70 kg. Dose-titration (up to a maximum dose of 300 mg) will be performed based upon regular measurement of Hb levels until the participant achieves central Hb value of =11.0 grams/deciliter (g/dL) and Hb increase from baseline (BL) of =1.0 g/dL at 2 consecutive study visits, separated by at least 5 days. Once target Hb level is reached, the participant will enter the maintenance period during which roxadustat dosage will be adjusted every 4 weeks to maintain participant's Hb level within the target range of 10.0 g/dL and 12.0 g/dL. The maximum treatment duration will be up to 234.9 weeks.

Placebo comparator: Placebo - Participants will receive roxadustat-matching placebo tablets orally TIW. The initial dose will be according to the tiered weight-based approach, with starting roxadustat-matching placebo doses of 70 mg TIW to participants weighing \<70 kg and roxadustat-matching placebo doses of 100 mg TIW to participants weighing =70 kg. Dose-titration (up to a maximum dose of 300 mg) will be performed based upon regular measurement of Hb levels until the participant achieves central Hb value of =11.0 g/dL and Hb increase from BL of =1.0 g/dL at 2 consecutive study visits, separated by at least 5 days. Once target Hb level is reached, the participant will enter the maintenance period during which roxadustat dosage will be adjusted every 4 weeks to maintain participant's Hb level within the target range of 10.0 g/dL and 12.0 g/dL. The maximum treatment duration will be up to 208.1 weeks.


Treatment: Drugs: Roxadustat
Oral tablets

Treatment: Drugs: Placebo
Oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
United States (US FDA) Submission: Mean Change From Baseline in Hb (g/dL) Over Weeks 28 to 52 Regardless of Rescue Therapy
Timepoint [1] 0 0
Baseline (Day 1, Week 0), Weeks 28 to 52
Primary outcome [2] 0 0
Ex-US Submission: Number (%) of Participants Who Achieved a Hb Response During the First 24-Weeks of Treatment Censoring for Rescue Therapy
Timepoint [2] 0 0
Baseline up to Week 24
Secondary outcome [1] 0 0
Mean Change From Baseline in Hb Averaged Over Weeks 28 to 36 With Censoring for Rescue Therapy
Timepoint [1] 0 0
Baseline (Day 1, Week 0), Weeks 28 to 36
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Baseline (Day 1, Week 0), Weeks 28 to 52
Secondary outcome [3] 0 0
Number (%) of Participants With Hb =10 g/dL Averaged Over Weeks 28 to 36 With Censoring for Rescue Therapy
Timepoint [3] 0 0
Weeks 28 to 36
Secondary outcome [4] 0 0
Mean Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28
Timepoint [4] 0 0
Baseline (Day 1, Week 0), Weeks 12 to 28
Secondary outcome [5] 0 0
Rate of Change in eGFR From Baseline up to 12 Months (Linear Random Coefficient Model With Observed Data)
Timepoint [5] 0 0
Baseline, Month 12
Secondary outcome [6] 0 0
Number of Participants Who Received Blood/RBC Transfusion in the First 52 Weeks of Treatment
Timepoint [6] 0 0
Baseline up to Week 52
Secondary outcome [7] 0 0
Number (%) of Participants Who Received Rescue Therapy in the First 24 Weeks and in the First 52 Weeks of Treatment
Timepoint [7] 0 0
Baseline (Day 1, Week 0) up to Week 24 and up to Week 52
Secondary outcome [8] 0 0
Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28
Timepoint [8] 0 0
Baseline (Day 1, Week 0), Weeks 12 to 28
Secondary outcome [9] 0 0
Number (%) of Participants Who Experienced Exacerbation of Hypertension
Timepoint [9] 0 0
Baseline up to Week 52
Secondary outcome [10] 0 0
Mean Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 20 to 28
Timepoint [10] 0 0
Baseline, Weeks 20 to 28

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/09/2018
Sample size
Target
Accrual to date
Final
922
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Investigational Site - Liverpool
Recruitment hospital [2] 0 0
Investigational Site - Gosford
Recruitment hospital [3] 0 0
Investigational Site - Hobart
Recruitment hospital [4] 0 0
Investigational Site - Launceston
Recruitment hospital [5] 0 0
Investigational Site - Melbourne
Recruitment hospital [6] 0 0
Investigational Site - New Lambton Heights
Recruitment hospital [7] 0 0
Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
7250 - Launceston
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [7] 0 0
2031 - Randwick
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Louisiana
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Massachusetts
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Michigan
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Missouri
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North Carolina
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Hamilton
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Tauranga
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Peru
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Callao
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Lima
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Cavite
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Hualien City
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Taichung
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Tainan
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Taipei
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Thailand
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Bangkok
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Thailand
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Chiang Mai

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
FibroGen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Astellas Pharma Europe B.V.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
AstraZeneca
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01750190
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Mark Eisner, MD, MPH
Address 0 0
FibroGen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01750190