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

FibroGen

Status and phase: Completed; Phase 4

Conditions: CKD Anemia in Dialysis Participants

Treatments: Drug: Roxadustat

Study type: Interventional

Funder types: Industry

Identifiers

NCT04059913

FGCL-4592-818

Details and patient eligibility

About

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)

Full 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.

Enrollment: 318 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

318 participants in 7 patient groups

Part 1: ESA-Naïve Participants - Low Weight Based Dosing

Experimental group

Description:

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.

Treatment:

Drug: Roxadustat

Part 1: ESA-Naïve Participants - Standard Weight Based Dosing

Experimental group

Description:

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.

Treatment:

Drug: Roxadustat

Part 1: ESA-Treated Participants - Low Weight Based Dosing

Experimental group

Description:

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.

Treatment:

Drug: Roxadustat

Part 1: ESA-Treated Participants - Standard Weight Based Dosing

Experimental group

Description:

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.

Treatment:

Drug: Roxadustat

Part 2: Roxadustat QW

Experimental group

Description:

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.

Treatment:

Drug: Roxadustat

Part 2: Roxadustat BIW

Experimental group

Description:

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.

Treatment:

Drug: Roxadustat

Part 2: Roxadustat TIW

Experimental group

Description:

Participants will receive roxadustat TIW. Roxadustat dose will continue per dose adjustment guideline.

Treatment:

Drug: Roxadustat