Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

Study Identifier:
ALXN2050-NEPH-201
ClinicalTrials.gov Identifier:
NCT05097989
EudraCT Identifier:
N/A
EU CT ID:
N/A
Sponsor:
Alexion Pharmaceuticals, Inc.
Study Contact Information:
N/A
Other

Study Details

Medical Condition
  • Lupus
  • Unmapped
  • IgAN
Study Drug
  • Drug: ALXN2050
  • Drug: Placebo
Date
Jan 2022 - Dec 2024
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18 - 75 Years
Requirements Information
Inclusion and Exclusion Criteria
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.
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.
Sex
Female & Male
Age
18 - 75 Years

Study Details

Medical Condition
  • Lupus
  • Unmapped
  • IgAN
Study Drug
  • Drug: ALXN2050
  • Drug: Placebo
Date
Jan 2022 - Dec 2024
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18 - 75 Years years
Requirements Information
Inclusion and Exclusion Criteria
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.
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.

Protocol 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.

Trial Locations

Location
Status
Location
Research Site
Huntsville, Alabama, United States, 35805
Status
N/A
Location
Research Site
Tucson, Arizona, United States, 85723
Status
N/A
Location
Research Site
La Jolla, California, United States, 92093
Status
N/A
Location
Research Site
Loma Linda, California, United States, 92350
Status
N/A
Location
Research Site
Northridge, California, United States, 91324
Status
N/A
Location
Research Site
Coral Springs, Florida, United States, 33065
Status
N/A
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