NCT05097989

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.

Trial Health

68
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2022

Typical duration for phase_2

Geographic Reach
16 countries

71 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 18, 2021

Completed
10 days until next milestone

First Posted

Study publicly available on registry

October 28, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

January 14, 2022

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 9, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 9, 2024

Completed
10 months until next milestone

Results Posted

Study results publicly available

October 15, 2025

Completed
Last Updated

October 15, 2025

Status Verified

September 1, 2025

Enrollment Period

2.9 years

First QC Date

October 18, 2021

Results QC Date

August 15, 2025

Last Update Submit

September 25, 2025

Conditions

Keywords

ALXN2050Complement Factor DComplement Alternative PathwayLNIgAN

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (13)

  • Both Cohorts: Percentage Change in Proteinuria From Baseline at Week 50

    Baseline, Week 50

  • Both Cohorts: Percentage of Participants Achieving >30% and >50% Reduction in Proteinuria at Week 26 and Week 50 Compared to Baseline

    Week 26 and Week 50

  • 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: Percentage of Participants Meeting the Criteria for Complete Renal Response at Week 26 and Week 50

    Week 26 and Week 50

  • LN Cohort: Percentage of Participants Meeting the Criteria for Partial Renal Response at Week 26 and Week 50

    Week 26 and Week 50

  • +8 more secondary outcomes

Study Arms (6)

LN Cohort: ALXN2050 180 mg

EXPERIMENTAL

Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.

Drug: ALXN2050

LN Cohort: ALXN2050 120 mg

EXPERIMENTAL

Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.

Drug: ALXN2050

LN Cohort: Placebo

PLACEBO COMPARATOR

Participants diagnosed with LN with an active flare will receive matched placebo in addition to standard-of-care background therapy.

Drug: Placebo

IgAN Cohort: ALXN2050 180 mg

EXPERIMENTAL

Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.

Drug: ALXN2050

IgAN Cohort: ALXN2050 120 mg

EXPERIMENTAL

Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.

Drug: ALXN2050

IgAN Cohort: Placebo

PLACEBO COMPARATOR

Participants diagnosed with IgAN will receive matched placebo in addition to standard-of-care background therapy.

Drug: Placebo

Interventions

Oral tablets

Also known as: ACH-0145228 (formerly)
IgAN Cohort: ALXN2050 120 mgIgAN Cohort: ALXN2050 180 mgLN Cohort: ALXN2050 120 mgLN Cohort: ALXN2050 180 mg

Oral tablets

IgAN Cohort: PlaceboLN Cohort: Placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (71)

Research Site

Huntsville, Alabama, 35805, United States

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Loma Linda, California, 92350, United States

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Northridge, California, 91324, United States

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Gainesville, Florida, 32603, United States

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Nampa, Idaho, 83687, United States

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Des Moines, Iowa, 50309, United States

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Kansas City, Missouri, 64111, United States

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Albuquerque, New Mexico, 87106, United States

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New York, New York, 10016, United States

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Houston, Texas, 77054, United States

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Ciudad de Buenos Aires, C1015ABO, Argentina

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Córdoba, 5000, Argentina

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La Plata, B1902COS, Argentina

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Rosario, S2000DEJ, Argentina

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Clayton, 3168, Australia

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Liverpool, 2170, Australia

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Nedlands, 6009, Australia

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Westmead, 2145, Australia

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Belo Horizonte, 30150-221, Brazil

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Curitiba, 80030-110, Brazil

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Juiz de Fora, 36010-570, Brazil

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Porto Alegre, 90035-003, Brazil

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Porto Alegre, 90480-000, Brazil

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Salvador, 40150-150, Brazil

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Guangzhou, 510080, China

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McKinney, 75069, China

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Shanghai, 200040, China

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Berlin, 10117, Germany

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Essen, 45122, Germany

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Mainz A. Rhein, 55131, Germany

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Mannheim, 68135, Germany

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Marburg, 30625, Germany

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München, 81377, DE, Germany

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Ashkelon, 78306, Israel

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Haifa, 3109601, Israel

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Petah Tikva, 4941492, Israel

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Ramat Gan, 52621, Israel

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Bari, 70124, Italy

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Brescia, 25123, Italy

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Milan, 20132, Italy

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Napoli, 80131, Italy

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Torino, 10154, Italy

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Guadalajara, 44140, Mexico

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México, 11570, Mexico

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Torreón, 27000, Mexico

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Niš, 18000, Serbia

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Novi Sad, 21000, Serbia

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Busan, 49241, South Korea

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Goyang-si, 10380, South Korea

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Seoul, 03080, South Korea

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Barcelona, 08025, Spain

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Barcelona, 8003, Spain

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Córdoba, 14004, Spain

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Girona, 17007, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Palma de Mallorca, 07120, Spain

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Seville, 41013, Spain

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Valencia, 46026, Spain

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Kaohsiung City, 833, Taiwan

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New Taipei City, 220, Taiwan

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New Taipei City, 23561, Taiwan

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Taichung, 40705, Taiwan

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Bangkok, 10400, Thailand

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Istanbul, 34093, Turkey (Türkiye)

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Bristol, BS105NB, United Kingdom

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Cambridge, CB2 0QQ, United Kingdom

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Doncaster, DN2 5LT, United Kingdom

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Leicester, LE5 4PW, United Kingdom

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London, E1 1BB, United Kingdom

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London, SE5 9RS, United Kingdom

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Research Site

Manchester, M13 9WL, United Kingdom

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Lupus NephritisGlomerulonephritis, IGA

Interventions

rhoA GTP-Binding Protein

Condition Hierarchy (Ancestors)

GlomerulonephritisNephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesLupus Erythematosus, SystemicConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

rho GTP-Binding ProteinsMonomeric GTP-Binding ProteinsGTP-Binding ProteinsGTP PhosphohydrolasesAcid Anhydride HydrolasesHydrolasesEnzymesEnzymes and CoenzymesCarrier ProteinsProteinsAmino Acids, Peptides, and ProteinsIntracellular Signaling Peptides and Proteins

Limitations and Caveats

The study intervention dosing and recruitment were paused, consistent with a data monitoring committee recommendation. Given the anticipated length of the dosing interruption that would have impacted data interpretation following dosing re-initiation, the sponsor decided to terminate the study.

Results Point of Contact

Title
Alexion Pharmaceuticals, Inc.
Organization
Alexion Pharmaceuticals, Inc.

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Masking of treatment allocation will be observed at least until Week 50.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 18, 2021

First Posted

October 28, 2021

Study Start

January 14, 2022

Primary Completion

December 9, 2024

Study Completion

December 9, 2024

Last Updated

October 15, 2025

Results First Posted

October 15, 2025

Record last verified: 2025-09

Locations