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

NCT01750190 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: FGCL-4592-060
• Study Type: interventional
• Target: 922
• Locations: 16 countries
• Sites: 145

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.

Conditions

CKD Anemia

Keywords

anemia; chronic kidney disease (CKD); non-dialysis; Hemoglobin (Hb); End-Stage Renal Disease; erythropoeitin; ASP1517; erythropoeisis stimulating-agent; AZD9941

Outcome Measures

Primary Outcomes (2)

• United States (US FDA) Submission: Mean Change From Baseline in Hb (g/dL) Over Weeks 28 to 52 Regardless of Rescue Therapy

  The change in Hb from baseline to the average level during the evaluation period (defined as Week 28 until Week 52) is reported. Hb values under the influence of a rescue therapy were not censored. The intermittent missing hemoglobin data were imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model, Monotone missing data were imputed by regression from its own treatment group. Baseline Hb was defined as the mean of up to 4 last central laboratory values prior to the first dose of study drug.

  Baseline (Day 1, Week 0), Weeks 28 to 52

• Ex-US Submission: Number (%) of Participants Who Achieved a Hb Response During the First 24-Weeks of Treatment Censoring for Rescue Therapy

  The number of participants who achieved a Hb response at 2 consecutive visits at least 5 days apart during the first 24 weeks of treatment, without rescue therapy (that is, red blood cell \[RBC\] transfusion, erythropoiesis-stimulating agent \[ESA\], or intravenous \[IV\] iron) are reported. A Hb response is defined, using central laboratory values, as the following: * Hb ≥11 g/dL and Hb increase from baseline by ≥1 g/dL in participants with baseline Hb \>8 g/dL, or * An increase in Hb by ≥2 g/dL in participants with baseline Hb ≤8.0 g/dL

  Baseline up to Week 24

Secondary Outcomes (10)

• Mean Change From Baseline in Hb Averaged Over Weeks 28 to 36 With Censoring for Rescue Therapy

  Baseline (Day 1, Week 0), Weeks 28 to 36

• Mean Change From Baseline in Hb Averaged Over Weeks 28 to 52 Regardless of Rescue Therapy in Participants With Baseline C-Reactive Protein (CRP) >Upper Limit of Normal (ULN)

  Baseline (Day 1, Week 0), Weeks 28 to 52

• Number (%) of Participants With Hb ≥10 g/dL Averaged Over Weeks 28 to 36 With Censoring for Rescue Therapy

  Weeks 28 to 36

• Mean Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28

  Baseline (Day 1, Week 0), Weeks 12 to 28

• Rate of Change in eGFR From Baseline up to 12 Months (Linear Random Coefficient Model With Observed Data)

  Baseline, Month 12

Study Arms (2)

Roxadustat

EXPERIMENTAL

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.

Drug: Roxadustat

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Roxadustat DRUG

Oral tablets

Also known as: FG-4592, ASP1517, AZD9941

Roxadustat

Placebo DRUG

Oral tablets

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kyntra Bio: lead
• Astellas Pharma Europe B.V.: collaborator
• AstraZeneca: collaborator

Study Sites (145)

Investigational Site

Huntsville, Alabama, 35801, United States

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Tempe, Arizona, 85284, United States

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Alhambra, California, 91801, United States

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Chula Vista, California, 91910, United States

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Inglewood, California, 90301, United States

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La Mesa, California, 91942, United States

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La Palma, California, 91324, United States

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Lynwood, California, 90262, United States

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Northridge, California, 91325, United States

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Paramount, California, 90723, United States

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Riverside, California, 92503, United States

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Roseville, California, 95661, United States

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San Dimas, California, 91773, United States

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Whittier, California, 90603, United States

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Coral Gables, Florida, 33134, United States

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Cutler Bay, Florida, 33157, United States

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Hialeah, Florida, 33016, United States

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Miami, Florida, 33015, United States

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Miami, Florida, 33122, United States

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Miami, Florida, 33135, United States

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Miami, Florida, 33150, United States

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Ocala, Florida, 34471, United States

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Pembroke Pines, Florida, 33028, United States

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South Miami, Florida, 33143, United States

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Winter Park, Florida, 32789, United States

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Augusta, Georgia, 30909, United States

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Caldwell, Idaho, 83605, United States

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Shreveport, Louisiana, 71101, United States

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Baltimore, Maryland, 21218, United States

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Boston, Massachusetts, 02215, United States

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Detroit, Michigan, 48202, United States

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Flint, Michigan, 48503, United States

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Flint, Michigan, 48532, United States

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Pontiac, Michigan, 48341, United States

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Roseville, Michigan, 48066, United States

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St Louis, Missouri, 63110, United States

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New Brunswick, New Jersey, 08903, United States

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Albuquerque, New Mexico, 87109, United States

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Mineola, New York, 11501, United States

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The Bronx, New York, 10461, United States

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Asheville, North Carolina, 28801, United States

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Raleigh, North Carolina, 27609, United States

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Rocky Mount, North Carolina, 27804, United States

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Winston-Salem, North Carolina, 27103, United States

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Beaver, Pennsylvania, 15009, United States

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Orangeburg, South Carolina, 29118, United States

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Sumter, South Carolina, 29150, United States

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Nashville, Tennessee, 37232, United States

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Arlington, Texas, 76015, United States

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Corsicana, Texas, 75110, United States

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Dallas, Texas, 75246, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78229, United States

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Fairfax, Virginia, 22033, United States

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Morgantown, West Virginia, 26506, United States

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Ciudad Evita, Buenos Aires, B1178IFA, Argentina

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González Catán, Buenos Aires, B1759LTF, Argentina

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Junín, Buenos Aires, B6000GMA, Argentina

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Morón, Buenos Aires, B1708DPN, Argentina

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Pergamino, Buenos Aires, B2700CPM, Argentina

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Villa Domínico, Buenos Aires, B1874GBA, Argentina

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Córdoba, Córdoba Province, X5002HWE, Argentina

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Buenos Aires, B1852FZD, Argentina

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Buenos Aires, C1425BPJ, Argentina

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Buenos Aires, C1429BWN, Argentina

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Corrientes, 3400, Argentina

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Córdoba, 5000, Argentina

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Córdoba, X5002AOQ, Argentina

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Córdoba, X5016KET, Argentina

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Mendoza, 5500, Argentina

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Salta, A4402BGJ, Argentina

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Santa Fe, 3000, Argentina

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Liverpool, New South Wales, 2170, Australia

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Gosford, 2250, Australia

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Hobart, 7000, Australia

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Launceston, 7250, Australia

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Melbourne, 3004, Australia

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New Lambton Heights, 2305, Australia

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Randwick, 2031, Australia

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Temuco, Región de la Araucanía, 4781151, Chile

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Santiago, Santiago Metropolitan, 8431657, 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, 852, Hong Kong

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Tai Po, Hong Kong

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Alor Star, 05460, Malaysia

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Kajang, 43000, Malaysia

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Kuala Lumpur, 50586, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Kuching, 93586, Malaysia

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Pulau Pinang, 10990, Malaysia

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Sungai Petani, 080000, Malaysia

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Taiping, 34000, Malaysia

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Guadalajara, Jalisco, 44280, Mexico

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Mexico City, Mexico City, 06100, Mexico

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Monterrey, Nuevo León, 64000, Mexico

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Mérida, Yucatán, 97133, Mexico

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Aguascalientes, 20128, Mexico

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San Luis Potosí City, 78240, Mexico

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Auckland, New Zealand

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Hamilton, 3240, New Zealand

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Tauranga, 3143, New Zealand

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San Martín de Porres, Lima region, Lima 31, Peru

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Bellavista, Provincia Constitucional del Callao, Callao 2, Peru

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Lima, Lima 13, Peru

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Lima, Lima 1, Peru

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Dasmariñas, Cavite, 4114, Philippines

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Davao City, Davao Region, 8000, Philippines

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Pasig, Philippines

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Quezon City, 1100, Philippines

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Quezon City, 1102, Philippines

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Ponce, 00716, Puerto Rico

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San Juan, 00918, Puerto Rico

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Singapore, 119074, Singapore

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Singapore, 768828, Singapore

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Singapore, Singapore

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Anyang-si, Gyeonggi-do, 431-796, South Korea

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Goyang-si, Gyeonggi-do, 410-719, South Korea

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Guri-si, Gyeonggi-do, 471-701, South Korea

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Seongnam-si, Gyeonggi-do, 463-712, South Korea

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Busan, 614-735, South Korea

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Seoul, 110-744, South Korea

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Seoul, 130-872, South Korea

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Seoul, 133-791, South Korea

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Seoul, 134-727, South Korea

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Seoul, 137-701, South Korea

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Seoul, 143-729, South Korea

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Seoul, South Korea

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Changhua, 500, Taiwan

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Hualien City, 970, Taiwan

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Kaohsiung City, 40705, Taiwan

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Kaohsiung City, 81362, Taiwan

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Kaohsiung City, 83301, Taiwan

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Taichung, 40705, Taiwan

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Taichung, 433, Taiwan

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Tainan, 433, Taiwan

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Tainan, 704, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 110, Taiwan

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Taipei, 11490, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Chiang Mai, 50200, Thailand

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Related Publications (3)

• 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.

  PMID: 36005278 DERIVED

• 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.

  PMID: 34362786 DERIVED

• 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.

  PMID: 33732977 DERIVED

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic; Kidney Failure, Chronic

Interventions

roxadustat

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: FibroGen, Inc.

060study@fibrogen.com

415-978-1441

Study Officials

• Mark Eisner, MD, MPH

  Kyntra Bio

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2012
• First Posted: December 17, 2012
• Study Start: November 5, 2012
• Primary Completion: September 24, 2018
• Study Completion: September 24, 2018
• Last Updated: October 1, 2021
• Results First Posted: October 1, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

CO (2); AU (7); HK (4); TW (12); PE (4); SG (3); CL (2); AR (17); NZ (3); PH (5); ME (6); TH (3); KR (12); PR (2); US (55); MY (8)