Study of Roxadustat (FG-4592) to Correct Anemia in Newly Initiated Dialysis Participants Not on Erythropoiesis-Stimulating Agent Treatment

NCT ID: NCT01414075

Last Updated: 2021-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-21
• Study Completion Date: 2013-01-10

Brief Summary

The purpose of this study is to evaluate efficacy and safety of roxadustat in the correction of anemia in participants with end-stage renal disease who recently started dialysis.

Detailed Description

Participants on hemodialysis (HD) will be randomized to 3 treatment arms (A, B, and C) of in a 1:1:1 ratio to receive no iron supplementation, oral iron supplementation, and IV iron supplementation, respectively, in addition to roxadustat. At the same time, participants on peritoneal dialysis (PD) will be enrolled into Arm D. Arm E will enroll either HD or PD participants, and is an optional, confirmatory/supplemental treatment arm with flexible dosing and flexible iron supplementation based on the evaluation of data from the previous 4 treatment arms.

Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low weight [40 to 60 kilograms {kg}], medium weight [>60 to 90 kg], and heavy weight [>90 to 140 kg] participants will receive 60, 100, and 140 milligrams [mg] roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 140, 200, and 300 mg for low, medium, and high weight participants, respectively) during Weeks 5 and 9, depending on the hemoglobin (Hb) level and rate of Hb rise in the previous 4 weeks.

Conditions

Dialysis; Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A + E (Participants on HD): Roxadustat Only, No Iron

Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally 3 times weekly (TIW) for 12 weeks.

Group Type: EXPERIMENTAL

Roxadustat

Intervention Type: DRUG

Tiered, weight-based dosing per schedule specified in the arm.

Arm B (Participants on HD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg

Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with iron (ferrous fumarate or ferrous gluconate) PO at doses containing elemental iron between 50 and 195 mg daily (depending on the type of iron formulation available in their countries) for 12 weeks.

Group Type: EXPERIMENTAL

Roxadustat

Intervention Type: DRUG

Tiered, weight-based dosing per schedule specified in the arm.

Oral Iron

Intervention Type: DRUG

Administered per oral dose and schedule specified in the arm.

Arm C (Participants on HD): IV Iron (Ferric Gluconate Complex in Sucrose or Equivalent) 60 mg

Participants on HD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with approximately 60 mg IV iron (ferric gluconate complex in sucrose injection \[for example, Ferrlecit®\] or equivalent) once a week for 12 weeks.

Group Type: EXPERIMENTAL

Roxadustat

Intervention Type: DRUG

Tiered, weight-based dosing per schedule specified in the arm.

IV Iron

Intervention Type: DRUG

Administered per IV dose and schedule specified in the arm.

Arm D (Participants on PD): PO Iron (Ferrous Fumarate or Ferrous Gluconate) Between 50 and 195 mg

Participants on PD will receive roxadustat capsules at the applicable dose (up to a maximum roxadustat dose of 140, 200, and 300 mg) based on weight and Hb level, administered orally TIW with iron (ferrous fumarate or ferrous gluconate) PO at doses containing elemental iron between 50 and 195 mg daily (depending on the type of iron formulation available in their countries) for 12 weeks.

Group Type: EXPERIMENTAL

Roxadustat

Intervention Type: DRUG

Tiered, weight-based dosing per schedule specified in the arm.

Oral Iron

Intervention Type: DRUG

Administered per oral dose and schedule specified in the arm.

Interventions

Roxadustat

Tiered, weight-based dosing per schedule specified in the arm.

Intervention Type: DRUG

Oral Iron

Administered per oral dose and schedule specified in the arm.

Intervention Type: DRUG

IV Iron

Administered per IV dose and schedule specified in the arm.

Intervention Type: DRUG

Other Intervention Names

FG-4592

Eligibility Criteria

Inclusion Criteria

• Receiving HD or PD for native kidney end-stage renal disease (ESRD) for 2 weeks to 4 months, prior to randomization
• Mean of the 2 most recent Hb values during the screening period, obtained at least 7 days apart, must be <10.0 grams (g)/deciliter (dL), with a difference of ≤1.0 g/dL between the 2 values
• Body weight 40 to 140 kilograms (kg)

Exclusion Criteria

• Previously received erythropoiesis-stimulating agents
• Received IV iron within 4 weeks of randomization
• Received red blood cell transfusion within 8 weeks prior to randomization or anticipated need for transfusion during the treatment period
• Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab)
• History of chronic liver disease
• Clinically significant infection
• New York Heart Association Class III or IV congestive heart failure
• History of malignancy, except the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps
• Chronic inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
• History of other blood disorders
• Active hemolysis or diagnosis of hemolytic syndrome
• Known bone marrow fibrosis
• Uncontrolled or symptomatic secondary hyperparathyroidism
• History of alcohol or drug abuse within a year prior to randomization, or anticipated inability to avoid consumption of more than 3 alcoholic beverages per day
• History of allergy or sensitivity to oral or IV iron therapy
• Seizure disorder or receiving anti-epilepsy medication for seizure disorder within 12 weeks prior to randomization
• Pregnant or breast-feeding females

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

FibroGen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Northridge, California, United States

Yuba City, California, United States

Detroit, Michigan, United States

Hong Kong, , Hong Kong

Moscow, , Russia

Saint Petersburg, , Russia

Singapore, , Singapore

Countries

United States; Hong Kong; Russia; Singapore

References

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.

Reference Type: DERIVED

PMID: 36005278 (View on PubMed)

Other Identifiers

FGCL-4592-053

Identifier Type: -

Identifier Source: org_study_id