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

NCT ID: NCT05097989

Last Updated: 2025-10-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-14
• Study Completion Date: 2024-12-09

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.

Conditions

Lupus Nephritis; Immunoglobulin A Nephropathy; IgAN; LN

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

LN Cohort: ALXN2050 180 mg

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

Group Type: EXPERIMENTAL

ALXN2050

Intervention Type: DRUG

Oral tablets

LN Cohort: ALXN2050 120 mg

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

Group Type: EXPERIMENTAL

ALXN2050

Intervention Type: DRUG

Oral tablets

LN Cohort: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral tablets

IgAN Cohort: ALXN2050 180 mg

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

Group Type: EXPERIMENTAL

ALXN2050

Intervention Type: DRUG

Oral tablets

IgAN Cohort: ALXN2050 120 mg

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

Group Type: EXPERIMENTAL

ALXN2050

Intervention Type: DRUG

Oral tablets

IgAN Cohort: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral tablets

Interventions

ALXN2050

Oral tablets

Intervention Type: DRUG

Placebo

Oral tablets

Intervention Type: DRUG

Other Intervention Names

ACH-0145228 (formerly)

Eligibility 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:

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Huntsville, Alabama, United States

Research Site

Loma Linda, California, United States

Research Site

Northridge, California, United States

Research Site

Gainesville, Florida, United States

Research Site

Nampa, Idaho, United States

Research Site

Des Moines, Iowa, United States

Research Site

Kansas City, Missouri, United States

Research Site

Albuquerque, New Mexico, United States

Research Site

New York, New York, United States

Research Site

Houston, Texas, United States

Research Site

Ciudad de Buenos Aires, , Argentina

Research Site

Córdoba, , Argentina

Research Site

La Plata, , Argentina

Research Site

Rosario, , Argentina

Research Site

Clayton, , Australia

Research Site

Liverpool, , Australia

Research Site

Nedlands, , Australia

Research Site

Westmead, , Australia

Research Site

Belo Horizonte, , Brazil

Research Site

Curitiba, , Brazil

Research Site

Juiz de Fora, , Brazil

Research Site

Porto Alegre, , Brazil

Research Site

Porto Alegre, , Brazil

Research Site

Salvador, , Brazil

Research Site

Guangzhou, , China

Research Site

McKinney, , China

Research Site

Shanghai, , China

Research Site

Berlin, , Germany

Research Site

Essen, , Germany

Research Site

Mainz A. Rhein, , Germany

Research Site

Mannheim, , Germany

Research Site

Marburg, , Germany

Research Site

München, , Germany

Research Site

Ashkelon, , Israel

Research Site

Haifa, , Israel

Research Site

Petah Tikva, , Israel

Research Site

Ramat Gan, , Israel

Research Site

Bari, , Italy

Research Site

Brescia, , Italy

Research Site

Milan, , Italy

Research Site

Napoli, , Italy

Research Site

Torino, , Italy

Research Site

Guadalajara, , Mexico

Research Site

México, , Mexico

Research Site

Torreón, , Mexico

Research Site

Niš, , Serbia

Research Site

Novi Sad, , Serbia

Research Site

Busan, , South Korea

Research Site

Goyang-si, , South Korea

Research Site

Seoul, , South Korea

Research Site

Barcelona, , Spain

Research Site

Barcelona, , Spain

Research Site

Córdoba, , Spain

Research Site

Girona, , Spain

Research Site

L'Hospitalet de Llobregat, , Spain

Research Site

Palma de Mallorca, , Spain

Research Site

Seville, , Spain

Research Site

Valencia, , Spain

Research Site

Kaohsiung City, , Taiwan

Research Site

New Taipei City, , Taiwan

Research Site

New Taipei City, , Taiwan

Research Site

Taichung, , Taiwan

Research Site

Bangkok, , Thailand

Research Site

Istanbul, , Turkey (Türkiye)

Research Site

Bristol, , United Kingdom

Research Site

Cambridge, , United Kingdom

Research Site

Doncaster, , United Kingdom

Research Site

Leicester, , United Kingdom

Research Site

London, , United Kingdom

Research Site

London, , United Kingdom

Research Site

Manchester, , United Kingdom

Countries

United States; Argentina; Australia; Brazil; China; Germany; Israel; Italy; Mexico; Serbia; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38299639 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37528520 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=ALXN2050-NEPH-201&amp;attachmentIdentifier=65f241f9-cb8f-42ee-97ae-be75462d581b&amp;fileName=ALXN2050-NEPH-201_CSR_Synopsis_Redacted-v1.pdf&amp;versionIdentifier=

Related Info

Other Identifiers

2021-001426-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALXN2050-NEPH-201

Identifier Type: -

Identifier Source: org_study_id