A Study of Roxadustat for the Treatment of Anemia in Participants With Chronic Kidney Disease and Not Receiving Dialysis

NCT ID: NCT01750190

Last Updated: 2021-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 922 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-05
• Study Completion Date: 2018-09-24

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.

Detailed Description

There is a screening period of up to 6 weeks, a variable treatment period for individual participants. In order to complete the treatment period simultaneously for all study participants, the minimum treatment duration may be less than 52 weeks, with a maximum treatment duration of up to 3 years after the last participant is randomized, and a post-treatment follow-up period of 4 weeks. Participants who prematurely discontinued from treatment will be expected to complete the Early Termination (ET) and End of Study (EOS) visits. Such participants will be considered non-completers, but they will be expected to participate in long-term follow-up (LTFU) for cardiovascular events (CV) of interest, vital status, and hospitalizations until overall study closure unless the participant withdrew consent for this LTFU data collection. Participants were randomized in a 2:1 ratio to receive either roxadustat or placebo in a double-blind manner.

Conditions

CKD Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Roxadustat

Intervention Type: DRUG

Oral tablets

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral tablets

Interventions

Roxadustat

Oral tablets

Intervention Type: DRUG

Placebo

Oral tablets

Intervention Type: DRUG

Other Intervention Names

FG-4592; ASP1517; AZD9941

Eligibility Criteria

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

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

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

Sponsors

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

FibroGen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Eisner, MD, MPH

Role: STUDY_CHAIR

FibroGen

Locations

Investigational Site

Huntsville, Alabama, United States

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Tempe, Arizona, United States

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Alhambra, California, United States

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Chula Vista, California, United States

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Inglewood, California, United States

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La Mesa, California, United States

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La Palma, California, United States

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Lynwood, California, United States

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Northridge, California, United States

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Paramount, California, United States

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Riverside, California, United States

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Roseville, California, United States

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San Dimas, California, United States

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Whittier, California, United States

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Coral Gables, Florida, United States

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Cutler Bay, Florida, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Ocala, Florida, United States

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Pembroke Pines, Florida, United States

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South Miami, Florida, United States

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Winter Park, Florida, United States

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Augusta, Georgia, United States

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Caldwell, Idaho, United States

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Shreveport, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Flint, Michigan, United States

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Flint, Michigan, United States

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Pontiac, Michigan, United States

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Roseville, Michigan, United States

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St Louis, Missouri, United States

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New Brunswick, New Jersey, United States

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Albuquerque, New Mexico, United States

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Mineola, New York, United States

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The Bronx, New York, United States

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Asheville, North Carolina, United States

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Raleigh, North Carolina, United States

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Rocky Mount, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Beaver, Pennsylvania, United States

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Orangeburg, South Carolina, United States

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Sumter, South Carolina, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Corsicana, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Fairfax, Virginia, United States

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Morgantown, West Virginia, United States

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Ciudad Evita, Buenos Aires, Argentina

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González Catán, Buenos Aires, Argentina

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Junín, Buenos Aires, Argentina

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Morón, Buenos Aires, Argentina

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Pergamino, Buenos Aires, Argentina

Investigational Product

Villa Domínico, Buenos Aires, Argentina

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Córdoba, Córdoba Province, Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Corrientes, , Argentina

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Córdoba, , Argentina

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Córdoba, , Argentina

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Córdoba, , Argentina

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Mendoza, , Argentina

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Salta, , Argentina

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Santa Fe, , Argentina

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Liverpool, New South Wales, Australia

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Gosford, , Australia

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Hobart, , Australia

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Launceston, , Australia

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Melbourne, , Australia

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New Lambton Heights, , Australia

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Randwick, , Australia

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Temuco, Región de la Araucanía, Chile

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Santiago, Santiago Metropolitan, Chile

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Barranquilla, Atlántico, Colombia

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Bogota, Cundinamarca, Colombia

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Hong Kong, Pokfulam, Hong Kong

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Chai Wan, , Hong Kong

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Shatin, , Hong Kong

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Tai Po, , Hong Kong

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Alor Star, , Malaysia

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Kajang, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuching, , Malaysia

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Pulau Pinang, , Malaysia

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Sungai Petani, , Malaysia

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Taiping, , Malaysia

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Guadalajara, Jalisco, Mexico

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Mexico City, Mexico City, Mexico

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Monterrey, Nuevo León, Mexico

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Mérida, Yucatán, Mexico

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Aguascalientes, , Mexico

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San Luis Potosí City, , Mexico

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Auckland, , New Zealand

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Hamilton, , New Zealand

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Tauranga, , New Zealand

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San Martín de Porres, Lima region, Peru

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Bellavista, Provincia Constitucional del Callao, Peru

Investigational site

Lima, , Peru

Investigational Site

Lima, , Peru

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Dasmariñas, Cavite, Philippines

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Davao City, Davao Region, Philippines

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Pasig, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Ponce, , Puerto Rico

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San Juan, , Puerto Rico

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Singapore, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Anyang-si, Gyeonggi-do, South Korea

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Goyang-si, Gyeonggi-do, South Korea

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Guri-si, Gyeonggi-do, South Korea

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Seongnam-si, Gyeonggi-do, South Korea

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Busan, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Changhua, , Taiwan

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Hualien City, , Taiwan

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chiang Mai, , Thailand

Countries

United States; Argentina; Australia; Chile; Colombia; Hong Kong; Malaysia; Mexico; New Zealand; Peru; Philippines; Puerto Rico; Singapore; South Korea; Taiwan; Thailand

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)

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.

Reference Type: DERIVED

PMID: 34362786 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33732977 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

FGCL-4592-060

Identifier Type: -

Identifier Source: org_study_id