Lupus Nephritis (LN) Immunoglobulin A Nephropathy (IgAN) MedDRA version: 21.1 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.0 Level: PT Classification code 10021263 Term: IgA nephropathy System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: ALXN2050
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: N/A
CAS Number: 2086178-00-7
Current Sponsor code: ALXN2050
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Alexion Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: LN Cohort • Clinical diagnosis of SLE by 2019 American College of Rheumatology and European League Against Rheumatism criteria. • Diagnosis of 2018 Revised International Society of Nephrology/Renal Pathology Society classification (active focal or diffuse proliferative LN Class III or IV) confirmed by biopsy obtained = 6 months prior to Screening or during Screening Period. Participants may co-exhibit Class V disease. Participants with de novo or relapsing disease may be eligible. • Clinically active LN at Screening requiring/receiving immunosuppression induction treatment in the opinion of the Investigator. • Proteinuria with UPCR = 1 g/g based on one 24 hour urine collection during the Screening Period. IgAN Cohort • Established diagnosis of primary IgAN based on kidney biopsy obtained any time prior to or during the Screening Period. • Mean proteinuria = 1 g/day on 2 complete and valid 24 hour urine collections during the Screening Period. • For participants with a kidney biopsy performed > 1 year prior to Screening that was used for eligibility: Presence of hematuria as defined by a positive result for blood on urine dipstick or = 10 red blood cells (RBCs)/high power field (hpf) microscopy on urine sediment (documented by the local laboratory) during Screening Period. Presence of hematuria documented by the central laboratory may also be acceptable. • Compliance with stable and optimal dose of RAS inhibitor treatment including maximum allowed or tolerated ACE inhibitor and/or ARB dose for = 3 months prior to Screening with no expected change in dose during the Blinded Treatment Periods (through Week 50) (participants with established intolerance to RAS inhibitors may be included). • Controlled and stable blood pressure (defined as =65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: Both Cohorts: • eGFR = 30 milliliters/minute/1.73 squared meters during Screening calculated by Chronic Kidney Disease Epidemiology Collaboration. • For participants with eGFR 3 g d. Mycophenolate mofetil > 2 g/day (or equivalent) for = 8 consecutive weeks prior to Screening e. Prednisone or prednisone equivalent = 0.5 mg/kg/day for = 8 consecutive weeks prior to Screening • Uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 110 mmHg) on 2 or more measurements during the Screening Period. For IgAN Cohort: • Diagnosis of rapid progressive glomerulonephritis as measured by eGFR loss = 30% over a period of 3 months prior to or during the Screening Period. • Secondary etiologies of IgAN. • Prednisone or prednisone equivalent > 20 mg/day for > 14 consecutive days or any other systemic immunosuppression for the treatment of IgAN = 6 months prior to Screening • Blood pressure of = 140/90 mmHg during the Screening Period confirmed on 2 measures > 30 minutes apart.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of ALXN2050 to reduce proteinuria in participants with LN or IgAN;Secondary Objective: •To evaluate the efficacy of ALXN2050 to improve measures of kidney function in participants with LN or IgAN • PK/PD - To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of ALXN2050 in participants with LN or IgAN • Safety -To characterize the safety and tolerability of ALXN2050 in participants with LN or IgAN LN Cohort only: •To evaluate the efficacy of ALXN2050 on measures of kidney function in participants with LN IgAN Cohort Only: •To evaluate the efficacy of ALXN2050 on measures of kidney function in participants with IgAN ;Primary end point(s): 1) Percentage change in proteinuria ;Timepoint(s) of evaluation of this end point: 1) Week 26 (based on 24-hour urine collection[s]) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Percentage change in proteinuria 2) Achieving > 30% and > 50% reduction in proteinuria 3)Change from baseline in eGFR 4)PK/PD - Observed plasma concentrations of ALXN2050 5)PK/PD - Absolute values and change from baseline in plasma Bb concentration and serum AP activity 6) Safety - Incidence of TEAEs and TESAEs 7) Safety - Changes from baseline in laboratory assessments LN Cohort Only: 8) Meeting the criteria for complete renal response (CRR) 9) Meeting the criteria for partial renal response (PRR) 10) Time to the first occurrence of UPCR = 0.5 g/g as measured by spot urine sample 11) Achieving corticosteroid taper to 7.5 mg/day 12) Experience of a Renal Flare 13) Experience of an Extrarenal systemic lupus erythematosus (SLE) Flare 14) Meeting the criteria for treatment failure 15) Meeting the criteria for Suboptimal Response 16) Absolute values and change from baseline in serum albumin IgAN Cohort Only: 17) Meeting the criteria for partial remission;Timepoint(s) of evaluation of this end point: Week 12, Week 26, Week 50 PK/PD and Safety - over time | — |
Countries
Argentina, Australia, Brazil, China, Germany, Israel, Italy, Korea, Republic of, Mexico, Peru, Serbia, Spain, Taiwan, Thailand, Türkiye, United Kingdom, United States
Contacts
Public ContactEuropean Clinical Trial Information
Alexion Europe SAS
Outcome results
None listed