Introduction
Methods
Study Design
Study Participants
Study Drug
Assessments and End Points
Statistical Analysis
Results
Patient Demographics and Baseline Characteristics
Variable | Placebo TIW (n = 27) | Roxadustat 50 mg TIW starting dose (n = 27) | Roxadustat 70 mg TIW starting dose (n = 26) | Roxadustat 100 mg TIW starting dose (n = 27) | Roxadustat TIW pooled (n = 80) |
---|---|---|---|---|---|
Age (year) | 61.9 (10.6) | 67.3 (7.7) | 60.8 (8.8) | 65.0 (8.5) | 64.4 (8.7) |
Male sex, n (%) | 11 (40.7) | 14 (51.9) | 14 (53.8) | 11 (40.7) | 39 (48.8) |
Body weight (kg)a | 60.17 (8.72) | 59.88 (9.32) | 59.70 (10.09) | 57.64 (10.28) | 59.07 (9.83) |
Primary disease of CKD, n (%) | |||||
Chronic glomerulonephritis | 4 (14.8) | 8 (29.6) | 6 (23.1) | 7 (25.9) | 21 (26.3) |
Diabetic nephropathy | 11 (40.7) | 11 (40.7) | 10 (38.5) | 12 (44.4) | 33 (41.3) |
Chronic pyelonephritis | 0 | 0 | 0 | 1 (3.7) | 1 (1.3) |
Polycystic kidney disease | 4 (14.8) | 0 | 3 (11.5) | 2 (7.4) | 5 (6.3) |
Nephrosclerosis | 6 (22.2) | 5 (18.5) | 5 (19.2) | 4 (14.8) | 14 (17.5) |
Other | 2 (7.4) | 3 (11.1) | 2 (7.7) | 1 (3.7) | 6 (7.5) |
History of iron deficiency anaemia, n (%) | 1 (3.7) | 0 | 2 (7.7) | 2 (7.4) | 4 (5.0) |
Concomitant iron therapy (oral) useb | 7 (25.9) | 10 (37.0) | 8 (30.8) | 9 (33.3) | 27 (33.8) |
Folate (nmol/L) | 19.97 (8.13) | 18.76 (7.16) | 17.57 (6.88) | 18.18 (6.93) | 18.19 (6.92) |
Vitamin B12 (pmol/L) | 402.2 (244.6) | 363.3 (157.4) | 282.9 (118.3) | 309.2 (203.0) | 317.7 (165.1) |
eGFRc (mL/min/1.73 m2) | 16.3 (8.5) | 15.8 (6.3) | 17.3 (9.5) | 15.9 (7.5) | 16.3 (7.8) |
(min, max) | 6.0, 40.0 | 8.0, 28.0 | 7.0, 47.0 | 8.0, 31.0 | 7.0, 47.0 |
Hemoglobin (g/dL) | 9.3 (0.7) | 9.4 (0.6) | 9.4 (0.6) | 9.4 (0.5) | 9.4 (0.6) |
(min, max) | 7.9, 10.7 | 7.3, 10.2 | 7.9, 10.4 | 8.1, 10.1 | 7.3, 10.4 |
Ferritin (ng/mL) | 125.4 (74.1) | 119.7 (61.0) | 144.4 (99.7) | 129.8 (89.3) | 131.1 (84.2) |
(min–max) | (22.1–304.0) | (28.0–277.0) | (39.4–400.0) | (29.2–380.0) | (28.0–400.0) |
TSAT (%) | 26.8 (10.6) | 28.3 (8.2) | 29.7 (10.0) | 31.1 (11.8) | 29.7 (10.0) |
(min–max) | (12.5–58.1) | (12.4–50.0) | (15.5–65.9) | (10.4–62.0) | (10.4–65.9) |
Hepcidin (ng/mL) | 40.9 (26.2) | 37.8 (21.3) | 45.9 (25.8) | 36.3 (23.3) | 39.9 (23.6) |
(min–max) | (7.07–105.00) | (5.93–83.60) | (11.30–94.87) | (7.40–103.20) | (5.93–103.20) |
TIBC (µmol/L) | 45.4 (4.8) | 47.6 (9.8) | 45.5 (7.8) | 47.6 (9.0) | 46.9 (8.8) |
(min–max) | (35–54) | (33–82) | (32–67) | (36–81) | (32–82) |
Primary End Point
Variable | Placebo TIW (n = 27) | Roxadustat 50 mg TIW starting dose (n = 27) | Roxadustat 70 mg TIW starting dose (n = 26) | Roxadustat 100 mg TIW starting dose (n = 27) | Roxadustat TIW pooled (n = 80) |
---|---|---|---|---|---|
Baseline to week 2 | − 0.19 (0.45) | 0.45 (0.48) | 1.01 (0.61) | 1.20 (0.71) | 0.89 (0.68) |
Week 2 to week 4 | − 0.08 (0.49) | 0.42 (0.47) | 0.66 (0.48) | 0.92 (0.55) | 0.66 (0.53) |
Secondary Efficacy End Points
Exploratory Assessments
Variable | Placebo TIW (n = 27) | Roxadustat 50 mg TIW starting dose (n = 27) | Roxadustat 70 mg TIW starting dose (n = 26) | Roxadustat 100 mg TIW starting dose (n = 27) | Roxadustat TIW pooled (n = 80) |
---|---|---|---|---|---|
Ferritin (ng/mL) | |||||
Change from BL to EOFa | − 10.3 (23.2) | − 52.7 (24.5)‡ | − 69.9 (41.9)‡ | − 69.9 (37.8)‡ | − 63.8 (35.9)‡ |
p value | 0.03 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Change from BL to EOTa | − 16.5 (32.5) | − 38.5 (44.9)* | − 23.4 (52.7) | − 35.9 (63.4) | − 32.7 (53.9) |
p value | 0.01 | < 0.001 | 0.03 | 0.007 | < 0.001 |
TSAT (%) | |||||
Change from BL to EOFa | 0.5 (7.8) | − 6.4 (9.7)† | − 7.7 (15.0)* | − 9.7 (16.4)† | − 7.9 (13.9)† |
p value | 0.74 | 0.002 | 0.02 | 0.005 | < 0.001 |
Change from BL to EOTa | 0.2 (10.2) | − 4.2 (6.8) | 1.0 (14.9) | − 0.2 (13.3) | − 1.2 (12.2) |
p value | 0.90 | 0.004 | 0.73 | 0.93 | 0.40 |
Hepcidin (ng/mL) | |||||
Change from BL to EOFa | − 3.9 (19.9) | − 24.3 (18.2)‡ | − 36.1 (26.3)‡ | − 27.4 (27.0)‡ | − 29.2 (24.3)‡ |
p value | 0.32 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Change from BL to EOTa | 2.4 (39.6) | − 12.5 (24.3) | − 3.3 (31.9) | − 13.0 (23.3) | − 9.7 (26.7) |
p value | 0.76 | 0.01 | 0.60 | 0.007 | 0.002 |
TIBC (µmol/L) | |||||
Change from BL to EOFa | 1.0 (3.6) | 9.8 (5.7)‡ | 12.0 (6.2)‡ | 13.8 (7.0)‡ | 11.9 (6.4)‡ |
p value | 0.16 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Change from BL to EOTa | 0.9 (3.9) | 9.2 (8.4)‡ | 4.6 (8.9) | 6.1 (6.5)‡ | 6.7 (8.1)‡ |
p value | 0.25 | < 0.001 | 0.01 | < 0.001 | < 0.001 |
Transferrin (g/L) | |||||
Change from BL to EOFa | 0.02 (0.1) | 0.5 (0.3)‡ | 0.6 (0.3)‡ | 0.7 (0.3)‡ | 0.6 (0.3)‡ |
p value | 0.45 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Change from BL to EOTa | 0.03 (0.2) | 0.4 (0.4)‡ | 0.2 (0.4) | 0.3 (0.3)‡ | 0.3 (0.4)‡ |
p value | 0.39 | < 0.001 | 0.02 | < 0.001 | < 0.001 |
Erythropoietin (IU/L) | |||||
Change from BL to EOF | 0.219 (1.804) | 9.819 (19.453) | 25.600 (47.357) | 59.363 (85.774) | 31.669 (60.770) |
Change from BL to EOT | 0.444 (2.644) | 23.807 (114.180) | 14.192 (69.717) | 19.837 (79.420) | 19.343 (88.996) |
Clinical Laboratory Evaluations
Safety and Treatment-Emergent Adverse Events
Placebo TIW (n = 27) | Roxadustat 50 mg TIW starting dose (n = 27) | Roxadustat 70 mg TIW starting dose (n = 26) | Roxadustat 100 mg TIW starting dose (n = 27) | Roxadustat TIW pooled (n = 80) | |
---|---|---|---|---|---|
Overall | 19 (70.4) | 20 (74.1) | 23 (88.5) | 20 (74.1) | 63 (78.8) |
Drug-related adverse events | 4 (14.8) | 10 (37.0) | 4 (15.4) | 5 (18.5) | 19 (23.8) |
Deaths | 0 | 0 | 0 | 0 | 0 |
Adverse events leading to discontinuation | 2 (7.4) | 8 (29.6) | 0 | 3 (11.1) | 11 (13.8) |
Serious adverse events | 2 (7.4) | 6 (22.2) | 2 (7.7) | 3 (11.1) | 11 (13.8) |
Drug-related serious adverse events | 0 | 1 (3.7) | 0 | 1 (3.7) | 2 (2.5) |
Drug-related serious adverse events leading to discontinuation | 1 (3.7) | 2 (7.4) | 0 | 1 (3.7) | 3 (3.8) |
Treatment-emergent adverse events occurring in > 5% of pooled roxadustat or placebo-treated patients by system organ class preferred terma | |||||
Gastrointestinal | 2 (7.4) | 8 (29.6) | 9 (34.6) | 5 (18.5) | 22 (27.5) |
Diarrhea | 1 (3.7) | 3 (11.1) | 4 (15.4) | 1 (3.7) | 8 (10.0) |
Nausea | 0 | 2 (7.4) | 3 (11.5) | 0 | 5 (6.3) |
Infections/infestations | 9 (33.3) | 7 (25.9) | 14 (53.8) | 11 (40.7) | 32 (40.0) |
Nasopharyngitis | 6 (22.2) | 5 (18.5) | 8 (30.8) | 8 (29.6) | 21 (26.3) |
Renal/urinary disorders | 1 (3.7) | 4 (14.8) | 0 | 1 (3.7) | 5 (6.3) |
Declining kidney functionb | 1 (3.7) | 4 (14.8) | 0 | 1 (3.7) | 5 (6.3) |
Musculoskeletal and connective tissue disorders | 4 (14.8) | 3 (11.1) | 4 (15.4) | 4 (14.8) | 11 (13.8) |
Muscle spasms | 2 (7.4) | 0 | 1 (3.8) | 0 | 1 (1.3) |
Respiratory, thoracic, and mediastinal disorders | 2 (7.4) | 2 (7.4) | 2 (7.7) | 1 (3.7) | 5 (6.3) |
Cough | 2 (7.4) | 0 | 0 | 1 (3.7) | 1 (1.3) |