Study of ALXN2050 in Proliferative Lupus Nephretis (LN) and Immunoglobulin A Nephropathy (IgAN)

Phase 1

• Conditions: upus Nephritis (LN)Immunoglobulin A Nephropathy (IgAN); MedDRA version: 21.1Level: PTClassification code 10025140Term: Lupus nephritisSystem Organ Class: 10038359 - Renal and urinary disorders; MedDRA version: 20.0Level: PTClassification code 10021263Term: IgA nephropathySystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2021-001426-22-DE
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-03
• Last Update Posted: 21 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 126

Inclusion Criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 113
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

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:
a. = 50% interstitial fibrosis and tubular atrophy
b. = 50% glomerular sclerosis
c. = 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).

For LN Cohort:
• Participants who have initiated any of the following treatments for the current active LN flare:
a. Cyclophosphamide = 6 months prior to Screening
b. CNIs = 1 month prior to Screening
c. A cumulative dose of intravenous (IV) methylprednisolone > 3 g
d. Mycophenolate mofetil > 2 g/day (or equivalent) for = 8 consecutive weeks prior to Screening
e. 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.

For 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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •To evaluate the efficacy of ALXN2050 to reduce proteinuria in participants with LN or IgAN;Secondary Objective: •To evaluate the efficacy of ALXN2050 to improve measures of kidney function in participants with LN or IgAN<br>• PK/PD - To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of ALXN2050 in participants with LN or IgAN<br>• Safety -To characterize the safety and tolerability of ALXN2050 in participants with LN or IgAN<br><br>LN Cohort only:<br>•To evaluate the efficacy of ALXN2050 on measures of kidney function in participants with LN<br><br>IgAN Cohort Only:<br>•To evaluate the efficacy of ALXN2050 on measures of kidney function in participants with IgAN<br>;Primary end point(s): 1) Percentage change in proteinuria ;Timepoint(s) of evaluation of this end point: 1) Week 26 (based on 24-hour urine collection[s])