Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02988973 | A Study of Intermittent Oral Dosing of ASP1517 in Non-Dialysis Chronic Kidney Disease Patients With Anemia | PHASE3 | COMPLETED | 334 | — | — | Jan 12, 2017 | Mar 26, 2020 | Oct 31, 2024 | 66 | Japan |
| NCT02964936 | A Study of Intermittent Oral Dosing of ASP1517 in ESA-untreated Chronic Kidney Disease Patients With Anemia | PHASE3 | COMPLETED | 100 | — | — | Jan 11, 2017 | Aug 15, 2018 | Oct 31, 2024 | 38 | Japan |
| NCT01630889 | Open-Label Extension Study for the Long-Term Efficacy and Safety of Roxadustat in Participants With Dialysis and Non-Dialysis Chronic Kidney Disease | PHASE2 | COMPLETED | 15 | — | — | May 18, 2012 | Dec 12, 2019 | Oct 1, 2021 | 7 | United States, Puerto Rico |
| NCT01244763 | Study of Roxadustat in Non-Dialysis Chronic Kidney Disease Participants With Anemia | PHASE2 | COMPLETED | 145 | — | — | Oct 29, 2010 | Jun 13, 2012 | Feb 10, 2022 | 38 | United States, Puerto Rico |
| NCT00761657 | Phase 2 Study of Roxadustat in Participants With Anemia and Chronic Kidney Disease Not Requiring Dialysis | PHASE2 | COMPLETED | 117 | — | — | Nov 1, 2006 | Jun 21, 2010 | Nov 19, 2021 | 34 | United States |
Hb response is defined as reaching target values for Hb.
Hb baseline was defined as the mean of the central laboratory Hb value from the baseline visit at Day 1 (prior to receiving the first dose of study drug in this study), plus any other central lab Hb values within 15 days prior to Day 1 regardless of fasting. The specific duration over which the participants were assessed was identified as "over time" for the endpoint in the study protocol. Therefore, to be consistent with the endpoint in the study protocol, an individual timepoint was not identified for this primary outcome measure.
An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL.
An adverse event (AE) was any untoward medical event in a participant who received study drug whether or not the event is considered drug related. TEAEs defined as an AE beginning after first dose of study drug until 28 days after last dose of study drug or existing AEs that worsened after first dose of study drug until the participant's last study visit. Severe AEs defined as incapacitating, inability to perform usual activities. Drug-related TEAEs defined as TEAEs with possible, probable, or definite relationship to study drug. Serious AE criteria included death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed here. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline was defined as the mean of last 3 available values prior to the first dose.
Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline is defined as the mean of last 3 available values prior to the first dose.
| Arm | Type | Description |
|---|---|---|
| rHuEPO or DA to ASP1517 | EXPERIMENTAL | Participants will receive roxadustat according to the prior randomization treatment, with starting doses of 70mg thrice weekly (TIW) to participants on \<4500 IU/week of rHuEPO or \<20 microgram (μg)/week of darbepoetin alfa (DA) and 100mg TIW to participants on ≥4500 IU/week rHuEPO or ≥ 20 μg/week DA. Participants roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300 mg. |
| rHuEPO or DA to DA | EXPERIMENTAL | Participants will receive DA according to the prior randomization treatment, with starting doses of 15 μg/2weeks to participants on ≤ 1500 IU/week of rHuEPO or \<11.25 microgram (μg)/week of DA, 30μg/2weeks to participants on \>1500 to \<6000 IU/week of rHuEPO or ≥ 11.25 to \< 22.5 μg/week of DA, 60μg/2weeks to participants on ≥ 6000 IU/week of rHuEPO or ≥ 22.5 to \< 37.5 μg/week of DA, 90μg/2weeks to participants on ≥ 37.5 to \< 52.5 μg/week of DA, 120μg/2weeks to participants on ≥ 52.5 to \< 75 μg/week of DA, 180μg/2weeks to participants on ≥ 75 μg/week of DA. Participant's roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 15, 30, 60, 90, 120, and 180 μg. |
| Epoetin beta pegol to ASP1517 | EXPERIMENTAL | Participants will receive roxadustat according to the prior registration treatment, with starting doses of 70mg thrice weekly (TIW) to participants on ≤100 μg/week of Epoetin beta pegol and 100mg TIW to participants on \>100 μg/week of Epoetin beta pegol. Participant's roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300 mg. |
| ASP1517 Low dose group | EXPERIMENTAL | Study drug will be dosed three times weekly for 24 weeks and dose adjustments will be made during the study. |
| ASP1517 High dose group | EXPERIMENTAL | Study drug will be dosed three times weekly for 24 weeks and dose adjustments will be made during the study. |
| Roxadustat | EXPERIMENTAL | Participants previously randomized to roxadustat will receive roxadustat at the same dose and frequency assigned at the last dose in the previous FibroGen study. Dose adjustments will be implemented (up to a maximum roxadustat dose of 3.0 mg/kg or 400 mg, whichever is lower) every 4 weeks to maintain Hb levels at 10.0-12 grams (g)/deciliter (dL). However, if a participant, at any dose, experiences an event of excessive hematopoiesis then the participant's dose will be immediately reduced, or an event of rapidly declining Hb then the participant's dose will be immediately increased. Participants will be permitted to receive roxadustat for up to 8 years. |
| Cohort A: Roxadustat Tiered, Weight Based Dosing TIW | EXPERIMENTAL | Participants will receive roxadustat capsules, administered orally 3 times weekly (TIW) for 16 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight \[45 to 60 kilograms (kg)\], 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 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. |
| Cohort B: Roxadustat Tiered, Weight Based Dosing TIW then BIW | EXPERIMENTAL | Participants will receive roxadustat capsules orally for 16 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight \[45 to 60 kg\], medium-weight \[\>60 to 90 kg\], and heavy-weight \[\>90 to 140 kg\] participants will receive 60, 100, and 140 mg roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from TIW to 2 times a week (BIW) at the time of the initial Hb response. |
| Cohort C: Roxadustat at 50 mg TIW | EXPERIMENTAL | Participants will receive roxadustat capsules at 50 mg, administered orally TIW for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 10.5-12 g/dL. |
| Cohort D: Roxadustat at 100 mg TIW | EXPERIMENTAL | Participants will receive roxadustat capsules at 100 mg, administered orally TIW for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 10.5-12 g/dL. |
| Cohort E: Roxadustat Tiered, Weight Based Dosing BIW then QW | EXPERIMENTAL | Participants will receive roxadustat capsules for 24 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight \[45 to 60 kg\], medium-weight \[\>60 to 90 kg\], and heavy-weight \[\>90 to 140 kg\] participants will receive 70, 100, and 150 mg roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.5 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from BIW to 1 time a week (QW) at the time of the initial Hb response. |
| Cohort F: Roxadustat at 70 mg BIW then QW | EXPERIMENTAL | Participants will receive roxadustat capsules at 70 mg for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.5 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from TIW to BIW at the time of the initial Hb response. Then after \>8 weeks of stable Hb, dose frequency will be reduced from BIW to QW. |
| Roxadustat 0.7 mg/kg BIW | EXPERIMENTAL | Participants will receive roxadustat 0.7 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days. |
| Roxadustat 0.7 mg/kg TIW | EXPERIMENTAL | Participants will receive roxadustat 0.7 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days. |
| Roxadustat 1.0 mg/kg BIW | EXPERIMENTAL | Participants will receive roxadustat 1.0 mg/kg BIW orally with doses administered at least 72 hours apart for 29 days. |
| Roxadustat 1.0 mg/kg TIW | EXPERIMENTAL | Participants will receive roxadustat 1.0 mg/kg TIW orally with doses administered at least 48 hours apart for 26 days. |
| Roxadustat 1.5 mg/kg BIW | EXPERIMENTAL | Participants will receive roxadustat 1.5 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days. |
| Roxadustat 1.5 mg/kg TIW | EXPERIMENTAL | Participants will receive roxadustat 1.5 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days. |
| Roxadustat 2.0 mg/kg BIW | EXPERIMENTAL | Participants will receive roxadustat 2.0 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days. |
| Roxadustat 2.0 mg/kg TIW | EXPERIMENTAL | Participants will receive roxadustat 2.0 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo orally, matching to the roxadustat dose, number of days per week, and duration. |
| Name | Type | Description |
|---|---|---|
| roxadustat | DRUG | Oral administration |
| DA | DRUG | Subcutaneous administration |
| Placebo | DRUG | Capsule |
Inclusion Criteria: * Subjects who were diagnosed with non-dialysis Chronic Kidney Disease and who are considered not to require renal replacement therapy during the study period * Subjects with renal anemia who have been receiving erythropoiesis stimulating agent (ESA) by subcutaneous injection an...