Methods related to the treatment of IgA nephropathy
The present disclosure relates to methods related to the treatment of IgA nephropathy. More specifically, the present disclosure relates to methods for treating a patient having IgA nephropathy (IgAN), to methods for reducing the serum Gd-IgA1 level in a patient having IgA nephropathy (IgAN), to methods for reducing the proteinuria in a patient having IgA nephropathy, to methods for reducing the serum Gd-IgA1 level and the proteinuria in a patient having IgA nephropathy, and further related disclosure.
1 . A method for treating a human patient having IgA nephropathy (IgAN), the method comprising:
administering to the human patient a therapeutically effective amount of atacicept, wherein:
(a) the atacicept is in an aqueous solution at a concentration of about 150 mg/ml;
(b) the atacicept solution has a pH of between about 4.9 and about 5.1;
(c) the patient has an estimated glomerular flow rate (eGFR) of about 35 mL/min/1.73 m2 or higher before the administration, wherein the eGFR is determined by a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; and
(d) the administration results in an at least 25% reduction in the serum level of galactose deficient immunoglobulin A1 (Gd-IgA1) in the patient, compared to before the administration.
2 . The method of claim 1 , wherein the patient has persistent proteinuria.
3 . The method of claim 2 , wherein the persistent proteinuria is a persistent proteinuria of 1.0 to 6.0 g/day of total protein based on 24-hour urine collection.
4 . The method of claim 2 , wherein:
(a) the persistent proteinuria is a persistent proteinuria with a urine protein:creatinine ratio (UPCR) of ≥1 mg/mg based on 24-hour urine collection; or
(b) the persistent proteinuria is a persistent proteinuria with a UPCR of ≥0.75 mg/mg based on 24-hour urine collection, wherein at least once within 12 months prior to the administration, the patient has been determined to have a UPCR of ≥1 mg/mg based on 24-hour urine collection.
5 . The method of claim 1 , wherein the patient has been treated with an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin receptor blocker (ARB), optionally for at least 8 weeks prior to the administration.
6 . The method of claim 1 , wherein the atacicept is administered at a dosage of at least 75 mg/week, optionally for a duration of at least 4 weeks.
7 . The method of claim 1 , wherein the atacicept is administered at a dosage of about 150 mg/week, optionally for a duration of at least 4 weeks.
8 . The method of claim 1 , wherein the route of administration is subcutaneous.
9 . The method of claim 1 , wherein the atacicept is obtained from mammalian cells comprising an expression construct encoding the atacicept.
10 . The method of claim 9 , wherein the mammalian cells are Chinese hamster ovary (CHO) cells.
11 . A method for treating a human patient having IgA nephropathy (IgAN), the method comprising administering to the human patient a therapeutically effective amount of atacicept, wherein:
(a) the atacicept is in an aqueous solution at a concentration of about 150 mg/ml;
(b) the atacicept solution has a pH of between about 4.9 and about 5.1;
(c) the patient has an estimated glomerular flow rate (eGFR) of about 35 mL/min/1.73m2 or higher before the administration, wherein the eGFR is determined by a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; and
(d) the administration results in the Estimated Glomerular Filtration Rate (eGFR) of the patient (i) increasing, (ii) remaining stable, or (iii) decreasing by not more than 10%, compared to before the administration.
12 . The method of claim 11 , wherein the patient has persistent proteinuria.
13 . The method of claim 12 , wherein the persistent proteinuria is a persistent proteinuria of 1.0 to 6.0 g/day of total protein based on 24-hour urine collection.
14 . The method of claim 12 , wherein:
(a) the persistent proteinuria is a persistent proteinuria with a urine protein: creatinine ratio (UPCR) of ≥1 mg/mg based on 24-hour urine collection; or
(b) the persistent proteinuria is a persistent proteinuria with a UPCR of ≥0.75 mg/mg based on 24-hour urine collection, wherein at least once within 12 months prior to the administration, the patient has been determined to have a UPCR of ≥1 mg/mg based on 24-hour urine collection.
15 . The method of claim 11 , wherein the patient has been treated with an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin receptor blocker (ARB), optionally for at least 8 weeks prior to the administration.
16 . The method of claim 11 , wherein the atacicept is administered at a dosage of at least 75 mg/week, optionally for a duration of at least 4 weeks.
17 . The method of claim 11 , wherein the atacicept is administered at a dosage of about 150 mg/week, optionally for a duration of at least 4 weeks.
18 . The method of claim 11 , wherein the route of administration is subcutaneous.
19 . The method of claim 11 , wherein the atacicept is obtained from mammalian cells comprising an expression construct encoding the atacicept.
20 . The method of claim 19 , wherein the mammalian cells are Chinese hamster ovary (CHO) cells.
21 . A method for treating a human patient having IgA nephropathy (IgAN), the method comprising administering to the human patient a therapeutically effective amount of atacicept, wherein:
(a) the atacicept is in an aqueous solution at a concentration of about 150 mg;ml;
(b) the atacicept solution has a pH of between about 4.9 and about 5.1;
(c) the patient has an estimated glomerular flow rate (eGFR) of about 35 mL/min/1.73m2 or higher before the administration, wherein the eGFR is determined by a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; and
(d) the administration results in an at least a 25% reduction in urine protein: creatinine ratio (UPCR) based on a 24-hour urine collection, compared to before the administration.
22 . The method of claim 21 , wherein the patient has persistent proteinuria.
23 . The method of claim 22 , wherein the persistent proteinuria is a persistent proteinuria of 1.0 to 6.0 g/day of total protein based on 24-hour urine collection.
24 . The method of claim 22 , wherein:
(a) the persistent proteinuria is a persistent proteinuria with a urine protein: creatinine ratio (UPCR) of ≥1 mg/mg based on 24-hour urine collection; or
(b) the persistent proteinuria is a persistent proteinuria with a UPCR of ≥0.75 mg/mg based on 24-hour urine collection, wherein at least once within 12 months prior to the administration, the patient has been determined to have a UPCR of ≥1 mg/mg based on 24-hour urine collection.
25 . The method of claim 21 , wherein the patient has been treated with an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin receptor blocker (ARB), optionally for at least 8 weeks prior to the administration.
26 . The method of claim 21 , wherein the atacicept is administered at a dosage of at least 75 mg/week, optionally for a duration of at least 4 weeks.
27 . The method of claim 21 , wherein the atacicept is administered at a dosage of about 150 mg/week, optionally for a duration of at least 4 weeks.
28 . The method of claim 21 , wherein the route of administration is subcutaneous.
29 . The method of claim 21 , wherein the atacicept is obtained from mammalian cells comprising an expression construct encoding the atacicept.
30 . The method of claim 29 , wherein the mammalian cells are Chinese hamster ovary (CHO) cells.