Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Participants With Chronic Kidney Disease

Sponsor

FibroGen (Industry)

Overall Status

Completed

CT.gov ID

NCT04059913

Collaborator

(none)

318

Enrollment

Locations

Arms

30.2

Actual Duration (Months)

12.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
CKD Anemia in Dialysis Participants	Drug: Roxadustat	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

318 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 11, 2019

Actual Primary Completion Date :

Nov 19, 2021

Actual Study Completion Date :

Dec 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: ESA-Naïve Participants - Low Weight Based Dosing ESA-naïve participants will receive roxadustat 70 mg TIW for body weight 45 to <60 kg or 100 mg TIW for body weight ≥60 kg.	Drug: Roxadustat Roxadustat will be dosed orally per dose and schedule specified in the arm description. Other Names: FG-4592
Experimental: Part 1: ESA-Naïve Participants - Standard Weight Based Dosing ESA naïve participants will receive roxadustat 100 mg TIW for body weight 45 to <60 kg or 120 mg TIW for body weight ≥60 kg.	Drug: Roxadustat Roxadustat will be dosed orally per dose and schedule specified in the arm description. Other Names: FG-4592
Experimental: Part 1: ESA-Treated Participants - Low Weight Based Dosing ESA-treated participants will receive roxadustat 70 mg TIW for body weight 45 to <60 kg or 100 mg TIW for body weight ≥60 kg.	Drug: Roxadustat Roxadustat will be dosed orally per dose and schedule specified in the arm description. Other Names: FG-4592
Experimental: Part 1: ESA-Treated Participants - Standard Weight Based Dosing ESA treated participants will receive roxadustat 100 mg TIW for body weight 45 to <60 kg or 120 mg TIW for body weight ≥60 kg.	Drug: Roxadustat Roxadustat will be dosed orally per dose and schedule specified in the arm description. Other Names: FG-4592
Experimental: Part 2: Roxadustat QW Participants will receive roxadustat once a week (QW). Roxadustat dose will be 2-dose step increase from originally planned week 21 TIW per dose amount.	Drug: Roxadustat Roxadustat will be dosed orally per dose and schedule specified in the arm description. Other Names: FG-4592
Experimental: Part 2: Roxadustat BIW Participants will receive roxadustat twice a week (BIW). Roxadustat dose will be 1-dose step increase from originally planned week 21 TIW per dose amount.	Drug: Roxadustat Roxadustat will be dosed orally per dose and schedule specified in the arm description. Other Names: FG-4592
Experimental: Part 2: Roxadustat TIW Participants will receive roxadustat TIW. Roxadustat dose will continue per dose adjustment guideline.	Drug: Roxadustat Roxadustat will be dosed orally per dose and schedule specified in the arm description. Other Names: FG-4592

Outcome Measures

Primary Outcome Measures

Part 1 (ESA Naïve): Percentage of Participants who Achieved Hb ≥110 g/L in the First 20 Weeks [Weeks 1 to 20]
Part 1 (ESA Treated): Percentage of Participants who Achieved Mean Hb ≥100 g/L Averaged Over Weeks 17 to 21 Visits [Weeks 17 to 21]
Part 2: Mean Hb Value Averaged Over Weeks 33 to 37 Visits [Weeks 33 to 37]

Secondary Outcome Measures

Part 1: Mean Change in Hb Level From Baseline to Average Over Weeks 17 to 21 Visits [Baseline, Weeks 17 to 21]
Part 1 (ESA-Naïve): Percentage of Participants With Mean Hb (Averaged Weeks 17 to 21 Visits) ≥100 g/L [Weeks 17 to 21]
Part 2: Percentage of Participants With Mean Hb (Averaged Weeks 33 to 37 Visits) ≥100 g/L [Weeks 33 to 37]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab).
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.
History of malignancy, myelodysplastic syndrome, and multiple myeloma.
Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (for example, systemic lupus erythematosis [SLE], rheumatoid arthritis, celiac disease).
Clinically significant gastrointestinal bleeding.
Women of childbearing potential and men with sexual partners of child bearing potential who are not using adequate contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site	Hefei	Anhui	China	230601
2	Investigational Site	Lanzhou	Gansu	China	730030
3	Investigational Site	Guangzhou	Guangdong	China	510515
4	Investigational Site	Shenzhen	Guangdong	China	518020
5	Investigational Site	Nanning	Guangxi Province	China	530021
6	Investigational Site	Zhengzhou	Henan	China	450052
7	Investigational Site	Wuhan	Hubei	China	430060
8	Investigational Site	Changsha	Hunan	China	410008
9	Investigational Site	Baotou	Inner Mongolia Autonomous Region	China	014010
10	Investigational Site	Nanjing	Jiangsu	China	210009
11	Investigational Site	Nanchang	Jiangxi	China	330006
12	Investigational Site	Chang chun	Jilin	China	130021
13	Investigational Site	Shenyang	Liaoning	China	110004
14	Investigational Site	Shenyang	Liaoning	China	110122
15	Investigational Site	Taiyuan	Shanxi	China	030001
16	Investigational Site	Xi'an	Shanxi	China	710004
17	Investigational Site	Xi'an	Shanxi	China	710061
18	Investigational Site	Chengdu	Sichuan	China	610041
19	Investigational Site	Chengdu	Sichuan	China	610072
20	Investigational Site	Hangzhou	Zhejiang	China	310003
21	Investigational Site	Beijing		China	100044
22	Investigational Site	Beijing		China	100191
23	Investigational Site	Beijing		China	100730
24	Investigational Site	Shanghai		China	200025
25	Investigational Site	Tianjin		China	300052