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

A Phase 2, Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Efficacy and Safety of ALXN2050 in Adult Participants With Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

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.

Study Overview

• Status: Terminated
• Conditions: Lupus Nephritis; Immunoglobulin A Nephropathy; IgAN; LN
• Intervention / Treatment: Drug: Placebo; Drug: ALXN2050

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad de Buenos Aires, Argentina, C1015ABO
    • Research Site
  • Córdoba, Argentina, 5000
    • Research Site
  • La Plata, Argentina, B1902COS
    • Research Site
  • Rosario, Argentina, S2000DEJ
    • Research Site
• Australia
  • Clayton, Australia, 3168
    • Research Site
  • Liverpool, Australia, 2170
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
  • Westmead, Australia, 2145
    • Research Site
• Brazil
  • Belo Horizonte, Brazil, 30150-221
    • Research Site
  • Curitiba, Brazil, 80030-110
    • Research Site
  • Juiz de Fora, Brazil, 36010-570
    • Research Site
  • Porto Alegre, Brazil, 90035-003
    • Research Site
  • Porto Alegre, Brazil, 90480-000
    • Research Site
  • Salvador, Brazil, 40150-150
    • Research Site
• China
  • Guangzhou, China, 510080
    • Research Site
  • McKinney, China, 75069
    • Research Site
  • Shanghai, China, 200040
    • Research Site
• Germany
  • Berlin, Germany, 10117
    • Research Site
  • Essen, Germany, 45122
    • Research Site
  • Mainz A. Rhein, Germany, 55131
    • Research Site
  • Mannheim, Germany, 68135
    • Research Site
  • Marburg, Germany, 30625
    • Research Site
  • München, Germany, 81377, DE
    • Research Site
• Israel
  • Ashkelon, Israel, 78306
    • Research Site
  • Haifa, Israel, 3109601
    • Research Site
  • Petah Tikva, Israel, 4941492
    • Research Site
  • Ramat Gan, Israel, 52621
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Brescia, Italy, 25123
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Torino, Italy, 10154
    • Research Site
• Mexico
  • Guadalajara, Mexico, 44140
    • Research Site
  • México, Mexico, 11570
    • Research Site
  • Torreón, Mexico, 27000
    • Research Site
• Serbia
  • Niš, Serbia, 18000
    • Research Site
  • Novi Sad, Serbia, 21000
    • Research Site
• South Korea
  • Busan, South Korea, 49241
    • Research Site
  • Goyang-si, South Korea, 10380
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
• Spain
  • Barcelona, Spain, 08025
    • Research Site
  • Barcelona, Spain, 8003
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • Girona, Spain, 17007
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08907
    • Research Site
  • Palma de Mallorca, Spain, 07120
    • Research Site
  • Seville, Spain, 41013
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 833
    • Research Site
  • New Taipei City, Taiwan, 220
    • Research Site
  • New Taipei City, Taiwan, 23561
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
• Thailand
  • Bangkok, Thailand, 10400
    • Research Site
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34093
    • Research Site
• United Kingdom
  • Bristol, United Kingdom, BS105NB
    • Research Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • Doncaster, United Kingdom, DN2 5LT
    • Research Site
  • Leicester, United Kingdom, Le5 4PW
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site
  • London, United Kingdom, E1 1BB
    • Research Site
  • Manchester, United Kingdom, M13 9WL
    • Research Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Research Site
  • California
    • Loma Linda, California, United States, 92350
      • Research Site
    • Northridge, California, United States, 91324
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32603
      • Research Site
  • Idaho
    • Nampa, Idaho, United States, 83687
      • Research Site
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Research Site
  • Texas
    • Houston, Texas, United States, 77054
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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:

1. ≥ 50% interstitial fibrosis and tubular atrophy
2. ≥ 50% glomerular sclerosis

3. ≥ 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:

  1. Cyclophosphamide ≤ 6 months prior to Screening
  2. CNIs ≤ 1 months prior to Screening
  3. A cumulative dose of intravenous (IV) methylprednisolone > 3 g
  4. Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 8 consecutive weeks prior to Screening
  5. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LN Cohort: ALXN2050 180 mg; Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050; Oral tablets; Other Names: ACH-0145228 (formerly)
Experimental: LN Cohort: ALXN2050 120 mg; Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050; Oral tablets; Other Names: ACH-0145228 (formerly)
Placebo Comparator: LN Cohort: Placebo; Participants diagnosed with LN with an active flare will receive matched placebo in addition to standard-of-care background therapy.	Drug: Placebo; Oral tablets
Experimental: IgAN Cohort: ALXN2050 180 mg; Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050; Oral tablets; Other Names: ACH-0145228 (formerly)
Experimental: IgAN Cohort: ALXN2050 120 mg; Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050; Oral tablets; Other Names: ACH-0145228 (formerly)
Placebo Comparator: IgAN Cohort: Placebo; Participants diagnosed with IgAN will receive matched placebo in addition to standard-of-care background therapy.	Drug: Placebo; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Both Cohorts: Percentage Change in Proteinuria From Baseline at Week 26	Proteinuria, the presence of excess proteins in the urine, was assessed using 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated an improvement in symptoms.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Both Cohorts: Percentage Change in Proteinuria From Baseline at Week 50	Proteinuria, the presence of excess proteins in the urine, was assessed using 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated an improvement in symptoms.	Baseline, Week 50
Both Cohorts: Percentage of Participants Achieving >30% and >50% Reduction in Proteinuria at Week 26 and Week 50 Compared to Baseline	Proteinuria, the presence of excess proteins in the urine, was assessed using 24-hour urine collections obtained at designated timepoints. A reduction from baseline indicated an improvement in symptoms.	Week 26 and Week 50
Both Cohorts: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 26 and Week 50	Changes in kidney function were monitored using measurements of eGFR and calculated based on the Chronic Kidney Disease Epidemiology Collaboration formula. Results are reported in milliliters/minute/1.73 meters squared (mL/min/1.73 m^2). Estimates of change from baseline are least-square means based on a mixed-effect model for repeated measures model that included change from baseline as the response variable, treatment as independent variable and adjusts for covariates of baseline and the stratification factor at randomization. An increase in eGFR in response to treatment indicated an improvement in symptoms.	Baseline, Week 26 and Week 50
LN Cohort: Percentage of Participants Meeting the Criteria for Complete Renal Response at Week 26 and Week 50	Complete renal response was defined as a decrease in urine protein to creatinine ratio (UPCR) to ≤0.5 gram/gram (g/g), an eGFR rate >60 mL/min/1.73 m^2 or no eGFR reduction ≥20% from baseline, and no treatment failure. Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal systemic lupus erythematosus (SLE) flare, or suboptimal response.	Week 26 and Week 50
LN Cohort: Percentage of Participants Meeting the Criteria for Partial Renal Response at Week 26 and Week 50	Partial renal response was defined as a decrease in UPCR ≥50% compared to baseline, an eGFR rate >60 mL/min/1.73 m^2 or no eGFR reduction ≥20% from baseline, and no treatment failure. Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal SLE flare, or suboptimal response.	Week 26 and Week 50
LN Cohort: Time to the First Occurrence of UPCR ≤0.5 g/g as Measured by a Spot Urine Sample	UPCR was assessed using 24-hour urine collections obtained at designated time points. The time to the first occurrence of UPCR ≤0.5 g/g was summarized by spot urine sample analysis.	Up to Week 50
LN Cohort: Percentage of Participants Achieving Corticosteroid Taper to 7.5 mg/Day at Weeks 12, 26, and 50	A corticosteroid taper was carried out per protocol at the clinical discretion of the investigator.	Week 12, Week 26, And Week 50
LN Cohort: Percentage of Participants Experiencing a Renal Flare Through Week 50	Renal flare was determined in the opinion of the investigator and additional protocol-specified criteria. For participants who achieved a complete renal response, a renal flare was the reproducible recurrence of proteinuria ≥1g/g. For all other participants, a renal flare was either of the following: a reproducible increase of serum creatinine >25% higher than baseline or above the upper limit of normal (plus additional protocol-specified criteria) or a reproducible doubling of the UPCR from a 24-hour urine collection compared with the lowest previous value obtained after the first dose of study intervention.	Baseline Through Week 50
LN Cohort: Percentage of Participants Experiencing an Extrarenal SLE Flare Through Week 50	Extrarenal SLE flare was defined as an increase in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Safety of Estrogens in Lupus Erythematosus National Assessment modification ≥4 points that was not accounted for by proteinuria, hematuria, urinary cellular casts, hypocomplementemia, or an increase in anti-double-stranded DNA antibody level. The SLEDAI-2K is an instrument that was used to assesses the disease activity of extrarenal SLE flare across 18 disease descriptors. Each descriptor carried a weighted value ranging from 1-8, with the reported score calculated as the sum of these descriptors and ranging from 0 to 85. Higher scores represent increased degrees of disease activity.	Baseline Through Week 50
LN Cohort: Percentage of Participants Meeting the Criteria for Treatment Failure Through Week 50	Treatment failure was defined as the receipt of additional standard of care therapy at any time during the study for protocol-defined renal flare, severe extrarenal SLE flare, or suboptimal response.	Baseline through Week 50
LN Cohort: Change From Baseline in Serum Albumin at Week 26 and Week 50	For the determination of serum albumin, blood samples were obtained at designated time points. Results reported as grams/liter (g/L).	Baseline, Week 26 and Week 50
LN Cohort: Percentage of Participants Meeting the Criteria for Suboptimal Response Through Week 50	A suboptimal response was to be determined in the opinion of the investigator in addition to the following criterion: reproducible proteinuria ≤25% decreased compared to baseline based on UPCR on a 24-hour urine collection performed by a central laboratory.	Baseline Through Week 50
IgAN Cohort: Percentage of Participants Meeting the Criteria for Partial Remission at Week 26 And Week 50	Partial remission was defined as mean proteinuria <1 g/24 hours, based on two valid 24-hour urine collections obtained within 2 weeks prior to the study visit.	Week 26 and Week 50

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.
• Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2022
• Primary Completion (Actual): December 9, 2024
• Study Completion (Actual): December 9, 2024

Study Registration Dates

• First Submitted: October 18, 2021
• First Submitted That Met QC Criteria: October 18, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: IgAN; ALXN2050; LN; Complement Factor D; Complement Alternative Pathway
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Skin and Connective Tissue Diseases; Lupus Nephritis; Glomerulonephritis, IGA; Amino Acids, Peptides, and Proteins; Proteins; Hydrolases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Carrier Proteins; rho GTP-Binding Proteins; Monomeric GTP-Binding Proteins; GTP-Binding Proteins; GTP Phosphohydrolases; Acid Anhydride Hydrolases; rhoA GTP-Binding Protein
• Other Study ID Numbers: ALXN2050-NEPH-201; 2021-001426-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No