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

• Status: Not yet recruiting
• Trial end date: 2026-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study of ALXN2050 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alexion Pharmaceuticals

Criteria

Key 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.

• Presence of hematuria as defined by 1+ blood based on urine dipstick or ≥ 10 red blood cells/high power field microscopy on urine sediment (performed by the local laboratory) during Screening Period (only applicable if diagnostic biopsy is >2 years prior to Screening).

• Compliance with stable and optimal dose of RAS inhibitor treatment including maximum allowed or tolerated angiotensin converting enzyme inhibitor and/or angiotensin receptor blocker dose for ≥ 3 months prior to Screening with no expected change in dose during the study (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.

• More than or equal to 50% interstitial fibrosis, tubular atrophy, glomerular sclerosis, or crescent formation in glomeruli on most recent kidney biopsy prior or during the Screening Period.

• 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 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 received any of the following treatments:

1. Cyclophosphamide ≤ 6 months prior to Screening

2. Calcineurin inhibitors ≤ 3 months prior to Screening

3. A cumulative dose of intravenous methylprednisolone > 3 g for the current active renal flare

4. Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 4 consecutive weeks prior to Screening for the current active renal flare

5. Prednisone or prednisone equivalent ≥ 0.5 milligrams (mg)/kilogram/day for ≥ 4 consecutive weeks prior to Screening for the current active renal flare

• 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 for > 14 consecutive days or any other immunosuppression within 6 months prior to Screening.

• Blood pressure of ≥ 140/90 mmHg during the Screening Period confirmed on 2 measures > 30 minutes apart.