Clinical trial NCT04059913: Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Participants With Chronic Kidney Disease
Official title: A Prospective, Randomized, Open-Label, Multi-Center Study to Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Subjects With Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: CKD Anemia in Dialysis Participants
Keywords: Anemia
Chronic Kidney Disease Dialysis
hemoglobin
End stage renal disease
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
First posted: 2019-08-16
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, multi-center study in dialysis chronic kidney disease (CKD) participants to evaluate the efficacy and relative safety of different dosing regimens of roxadustat over a 36-week treatment period.

There are 3 study periods:

* Screening Period (up to 4 weeks)
* Treatment Period (36 weeks)

Part 1: Correction/Conversion Period (Weeks 1-20)

Part 2: Hemoglobin (Hb) Maintenance Period (Weeks 21-36)

* Follow-up Period (4 weeks)

Detailed description: Approximately 102 erythropoiesis stimulating agents (ESA)-naïve participants and 204 ESA-treated participants will be enrolled and randomized respectively in a 1:1 ratio to receive roxadustat at one of 2 starting doses as below:

* Low weight-based dosing: 70 milligrams (mg) 3 times a week (TIW) for body weight \<60 kilograms (kg) or 100 mg TIW for body weight ≥60 kg
* Standard weight-based dosing: 100 mg TIW for body weight \<60 kg or 120 mg TIW for body weight ≥60 kg

After 20 weeks of treatment, all eligible participants whose last 2 Hb levels ≥105 grams (g)/liter (L) and change in Hb over the most recent 4 weeks is \> - 10 g/L will switch to receive roxadustat for another 16 weeks to evaluate the efficacy and safety of new dosing regimens.

At the end of Week 36, all participants will discontinue roxadustat and enter a 4-week Follow-up Period.

Eligibility criteria: Inclusion Criteria:

1. CKD with end-stage renal disease (ESRD) on either hemodialysis (HD) or peritoneal dialysis (PD)

Exclusion Criteria:

1. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab).
2. Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thromboembolic event (for example, deep venous thrombosis or pulmonary embolism) within 26 weeks prior to Day 1.
3. History of malignancy, myelodysplastic syndrome, and multiple myeloma.
4. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (for example, systemic lupus erythematosis \[SLE\], rheumatoid arthritis, celiac disease).
5. Clinically significant gastrointestinal bleeding.
6. Women of childbearing potential and men with sexual partners of child bearing potential who are not using adequate contraception.

Primary outcomes:
measure: Part 1 (ESA Naïve): Percentage of Participants who Achieved Hb ≥110 g/L in the First 20 Weeks
timeFrame: Weeks 1 to 20
measure: Part 1 (ESA Treated): Percentage of Participants who Achieved Mean Hb ≥100 g/L Averaged Over Weeks 17 to 21 Visits
timeFrame: Weeks 17 to 21
measure: Part 2: Mean Hb Value Averaged Over Weeks 33 to 37 Visits
timeFrame: Weeks 33 to 37
Secondary outcomes:
measure: Part 1: Mean Change in Hb Level From Baseline to Average Over Weeks 17 to 21 Visits
timeFrame: Baseline, Weeks 17 to 21
measure: Part 1 (ESA-Naïve): Percentage of Participants With Mean Hb (Averaged Weeks 17 to 21 Visits) ≥100 g/L
timeFrame: Weeks 17 to 21
measure: Part 2: Percentage of Participants With Mean Hb (Averaged Weeks 33 to 37 Visits) ≥100 g/L
timeFrame: Weeks 33 to 37
Other outcomes:
Locations:
city: Hefei
country: China
facility: Investigational Site
state: Anhui
city: Lanzhou
country: China
facility: Investigational Site
state: Gansu
city: Guangzhou
country: China
facility: Investigational Site
state: Guangdong
city: Shenzhen
country: China
facility: Investigational Site
state: Guangdong
city: Nanning
country: China
facility: Investigational Site
state: Guangxi Province
city: Zhengzhou
country: China
facility: Investigational Site
state: Henan
city: Wuhan
country: China
facility: Investigational Site
state: Hubei
city: Changsha
country: China
facility: Investigational Site
state: Hunan
city: Baotou
country: China
facility: Investigational Site
state: Inner Mongolia Autonomous Region
city: Nanjing
country: China
facility: Investigational Site
state: Jiangsu
city: Nanchang
country: China
facility: Investigational Site
state: Jiangxi
city: Chang chun
country: China
facility: Investigational Site
state: Jilin
city: Shenyang
country: China
facility: Investigational Site
state: Liaoning
city: Shenyang
country: China
facility: Investigational Site
state: Liaoning
city: Taiyuan
country: China
facility: Investigational Site
state: Shanxi
city: Xi'an
country: China
facility: Investigational Site
state: Shanxi
city: Xi'an
country: China
facility: Investigational Site
state: Shanxi
city: Chengdu
country: China
facility: Investigational Site
state: Sichuan
city: Chengdu
country: China
facility: Investigational Site
state: Sichuan
city: Hangzhou
country: China
facility: Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: Investigational Site
city: Beijing
country: China
facility: Investigational Site
city: Beijing
country: China
facility: Investigational Site
city: Shanghai
country: China
facility: Investigational Site
city: Tianjin
country: China
facility: Investigational Site
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.