Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)
Phase 2
Terminated
- Conditions
- Lupus NephritisIgANLNImmunoglobulin A Nephropathy
- Interventions
- Drug: Placebo
- Registration Number
- NCT05097989
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study of ALXN2050 (120 and 180 milligrams \[mg\]) in addition to background therapy consistent with the standard of care in adult participants (≥ 18 to ≤ 75 years of age) with either LN or IgAN. The study will consist of an up to 6-week Screening Period, a 26-week blinded Initial Evaluation Period, a 24-week blinded Extended Treatment Period, and an Open-label Extension (OLE) Period of up to 2 years.
Safety will be monitored throughout the study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 100
Inclusion Criteria
Both Cohorts
- Participants on sodium-glucose cotransporter-2 (SGLT 2) inhibitors (eg, empagliflozin) must be on a stable dose for ≥ 3 months with no planned change in dose during the Blinded Treatment Periods (through Week 50).
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 < 140/90 millimeters of mercury [mmHg]) over the past 3 months prior to randomization.
Key
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 < 45 mL/min/1.73 m2 at Screening, presence of any of the following in glomeruli on most recent kidney biopsy prior to or during the Screening
Period:
-
≥ 50% interstitial fibrosis and tubular atrophy
-
≥ 50% glomerular sclerosis
-
≥ 50% active crescent formation
- Concomitant significant renal disease other than LN or IgAN on the most recent biopsy prior to or during the Screening Period.
- History of solid organ or bone marrow transplant, or planned transplant during the Blinded Extended Treatment Period (50 weeks).
- Splenectomy or functional asplenia.
- Known or suspected complement deficiency, unless attributable to underlying disease (that is, LN and IgAN).
- Bone marrow insufficiency with absolute neutrophil count < 1.3 × 10^3/microliter; thrombocytopenia (platelet count < 50,000/cubic millimeter).
LN Cohort
-
Participants who have initiated any of the following treatments for the current active LN flare:
- Cyclophosphamide ≤ 6 months prior to Screening
- CNIs ≤ 1 months prior to Screening
- A cumulative dose of intravenous (IV) methylprednisolone > 3 g
- Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 8 consecutive weeks prior to Screening
- 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.
-
Prior history or clinically active SLE-related cerebritis, seizures, stroke, or stroke syndrome requiring treatment or clinically active pericarditis
-
Inability to take or tolerate the standard of care background therapies
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LN Cohort: ALXN2050 180 mg ALXN2050 Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy. LN Cohort: ALXN2050 120 mg ALXN2050 Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy. LN Cohort: Placebo Placebo Participants diagnosed with LN with an active flare will receive matched placebo in addition to standard-of-care background therapy. IgAN Cohort: ALXN2050 180 mg ALXN2050 Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy. IgAN Cohort: Placebo Placebo Participants diagnosed with IgAN will receive matched placebo in addition to standard-of-care background therapy. IgAN Cohort: ALXN2050 120 mg ALXN2050 Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.
- Primary Outcome Measures
Name Time Method Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26 Baseline, Week 26 This will be based on 24-hour urine collection(s).
- Secondary Outcome Measures
Name Time Method Both Cohorts: Participants Achieving > 30% And > 50% Reduction In Proteinuria At Week 26 And Week 50 Compared To Baseline Baseline, Week 26 and Week 50 This will be based on 24-hour urine collection(s) at each time point.
Both Cohorts: Change From Baseline In Estimated Glomerular Filtration Rate (eGFR) At Week 26 And Week 50 Baseline, Week 26 and Week 50 LN Cohort: Participants Meeting The Criteria For Complete Renal Response At Week 26 And Week 50 Week 26 And Week 50 LN Cohort: Participants Achieving Corticosteroid Taper To 7.5 mg/Day At Weeks 12, 26, And 50 Week 12, Week 26, And Week 50 LN Cohort: Participants Experiencing A Renal Flare Through Week 50 Baseline through Week 50 Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 50 Baseline, Week 50 This will be based on 24-hour urine collection(s).
LN Cohort: Time To The First Occurrence Of Urine Protein To Creatinine Ratio (UPCR) ≤ 0.5 Gram/Gram (g/g) As Measured By Spot Urine Sample Up to Week 50 LN Cohort: Participants Meeting The Criteria For Partial Renal Response At Week 26 And Week 50 Week 26 And Week 50 LN Cohort: Participants Experiencing An Extrarenal Systemic Lupus Erythematosus (SLE) Flare Through Week 50 Baseline through Week 50 LN Cohort: Participants Meeting The Criteria For Treatment Failure Through Week 50 Baseline through Week 50 LN Cohort: Absolute Values And Change From Baseline In Serum Albumin At Week 26 And Week 50 Baseline, Week 26 and Week 50 IgAN Cohort: Participants Meeting The Criteria For Partial Remission At Week 26 And Week 50 Week 26 and Week 50 Both Cohorts: Observed Plasma Concentrations Of ALXN2050 Over Time Baseline through Week 50 Both Cohorts: Absolute Values And Change From Baseline In Plasma Concentration Of Bb Fragment Of Complement Factor B At Week 50 Baseline, Week 50 Both Cohorts: Absolute Values And Change From Baseline In Serum Alternative Pathway Activity At Week 50 Baseline, Week 50
Trial Locations
- Locations (1)
Research Site
🇬🇧Newcastle upon Tyne, United Kingdom