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

Lupus Nephritis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05097989
• Other study ID #: ALXN2050-NEPH-201
• Status: Recruiting
• Phase: Phase 2
• Start date: January 14, 2022
• Est. completion date: June 30, 2026

Study information

• Verified date: April 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: Alexion Pharmaceuticals, Inc. (Sponsor)
• Phone: 1-855-752-2356
• Email: clinicaltrials[@]alexion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgAN
• Immunoglobulin A Nephropathy
• Kidney Diseases
• Lupus Nephritis
• Nephritis

Intervention

Drug:
• ALXN2050
Oral tablets
• Placebo
Oral tablets

Locations

Country	Name	City	State
Argentina	Research Site	Ciudad Autonoma Bs As
Argentina	Research Site	Córdoba
Argentina	Research Site	La Plata
Argentina	Research Site	Mendoza
Argentina	Research Site	Rosario
Argentina	Research Site	San Miguel de Tucuman
Australia	Research Site	Clayton
Australia	Research Site	Heidelberg
Australia	Research Site	Liverpool
Australia	Research Site	Nedlands
Australia	Research Site	St Leonards
Australia	Research Site	Westmead
Brazil	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
China	Research Site	Chuangchun
China	Research Site	Guangzhou
China	Research Site	McKinney
China	Research Site	Nanchang
China	Research Site	Shanghai
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Essen
Germany	Research Site	Fulda
Germany	Research Site	Köln
Germany	Research Site	Luebeck
Germany	Research Site	Mainz A. Rhein
Germany	Research Site	Mannheim
Germany	Research Site	Munchen
Germany	Research Site	Regensburg
Israel	Research Site	Ashdod
Israel	Research Site	Ashkelon
Israel	Research Site	Haifa
Italy	Research Site	Bari
Italy	Research Site	Brescia
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Pavia
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Torino
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Mexico	Research Site	Ciudad de México
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexicali
Mexico	Research Site	Mexico
Mexico	Research Site	Torreon
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Omsk
Serbia	Research Site	Belgrade
Serbia	Research Site	Belgrade
Serbia	Research Site	Belgrade
Serbia	Research Site	Nis
Serbia	Research Site	Novi Sad
Spain	Research Site	Avilés
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Girona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Keelung
Taiwan	Research Site	New Taipei City
Taiwan	Research Site	Taichung
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Doncaster
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Des Moines	Iowa
United States	Research Site	Gainesville	Florida
United States	Research Site	Huntsville	Alabama
United States	Research Site	Kansas City	Missouri
United States	Research Site	La Jolla	California
United States	Research Site	Loma Linda	California
United States	Research Site	Nampa	Idaho
United States	Research Site	New York	New York
United States	Research Site	Northridge	California
United States	Research Site	Syracuse	New York
United States	Research Site	Vacaville	California

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  China,  Germany,  Israel,  Italy,  Korea, Republic of,  Mexico,  Peru,  Russian Federation,  Serbia,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 26	This will be based on 24-hour urine collection(s).	Baseline, Week 26
Secondary	Both Cohorts: Percentage Change In Proteinuria From Baseline To Week 50	This will be based on 24-hour urine collection(s).	Baseline, Week 50
Secondary	Both Cohorts: Participants Achieving > 30% And > 50% Reduction In Proteinuria At Week 26 And Week 50 Compared To Baseline	This will be based on 24-hour urine collection(s) at each time point.	Baseline, Week 26 and Week 50
Secondary	Both Cohorts: Change From Baseline In Estimated Glomerular Filtration Rate (eGFR) At Week 26 And Week 50		Baseline, Week 26 and Week 50
Secondary	LN Cohort: Participants Meeting The Criteria For Complete Renal Response At Week 26 And Week 50		Week 26 And Week 50
Secondary	LN Cohort: Participants Meeting The Criteria For Partial Renal Response At Week 26 And Week 50		Week 26 And Week 50
Secondary	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
Secondary	LN Cohort: Participants Achieving Corticosteroid Taper To 7.5 mg/Day At Weeks 12, 26, And 50		Week 12, Week 26, And Week 50
Secondary	LN Cohort: Participants Experiencing A Renal Flare Through Week 50		Baseline through Week 50
Secondary	LN Cohort: Participants Experiencing An Extrarenal Systemic Lupus Erythematosus (SLE) Flare Through Week 50		Baseline through Week 50
Secondary	LN Cohort: Participants Meeting The Criteria For Treatment Failure Through Week 50		Baseline through Week 50
Secondary	LN Cohort: Absolute Values And Change From Baseline In Serum Albumin At Week 26 And Week 50		Baseline, Week 26 and Week 50
Secondary	IgAN Cohort: Participants Meeting The Criteria For Partial Remission At Week 26 And Week 50		Week 26 and Week 50
Secondary	Both Cohorts: Observed Plasma Concentrations Of ALXN2050 Over Time		Baseline through Week 50
Secondary	Both Cohorts: Absolute Values And Change From Baseline In Plasma Concentration Of Bb Fragment Of Complement Factor B At Week 50		Baseline, Week 50
Secondary	Both Cohorts: Absolute Values And Change From Baseline In Serum Alternative Pathway Activity At Week 50		Baseline, Week 50