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

Alexion Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Immunoglobulin A Nephropathy; LN; Lupus Nephritis; IgAN

Treatments: Drug: Placebo; Drug: ALXN2050

Study type: Interventional

Funder types: Industry

Identifiers

NCT05097989

ALXN2050-NEPH-201

Details and patient eligibility

About

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.

Enrollment: 100 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 6 patient groups, including a placebo group

LN Cohort: ALXN2050 180 mg

Experimental group

Description:

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

Treatment:

Drug: ALXN2050

LN Cohort: ALXN2050 120 mg

Experimental group

Description:

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

Treatment:

Drug: ALXN2050

LN Cohort: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

IgAN Cohort: ALXN2050 180 mg

Experimental group

Description:

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

Treatment:

Drug: ALXN2050

IgAN Cohort: ALXN2050 120 mg

Experimental group

Description:

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

Treatment:

Drug: ALXN2050

IgAN Cohort: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo