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

Study identifier:ALXN2050-NEPH-201

ClinicalTrials.gov identifier:NCT05097989

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

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)

Medical condition

Lupus Nephritis, Immunoglobulin A nephropathy

Phase

Phase 2

Healthy volunteers

Study drug

ALXN2050, Placebo

Sex

All

Estimated Enrollment

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 14 Jan 2022

Estimated Primary Completion Date: 30 Jun 2026

Estimated Study Completion Date: 30 Jun 2026

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2024 by Alexion Pharmaceuticals, Inc.

Collaborators

Inclusion and exclusion 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:
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).
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 months 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.
- 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.

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Arms	Assigned Interventions
Experimental: LN Cohort: ALXN2050 180 mg Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050 Oral tablets Other Name: ACH-0145228 (formerly)
Experimental: LN Cohort: ALXN2050 120 mg Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050 Oral tablets Other Name: ACH-0145228 (formerly)
Placebo Comparator: LN Cohort: Placebo Participants diagnosed with LN with an active flare will receive matched placebo in addition to standard-of-care background therapy.	Drug: Placebo Oral tablets
Experimental: IgAN Cohort: ALXN2050 180 mg Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050 Oral tablets Other Name: ACH-0145228 (formerly)
Experimental: IgAN Cohort: ALXN2050 120 mg Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.	Drug: ALXN2050 Oral tablets Other Name: ACH-0145228 (formerly)
Placebo Comparator: IgAN Cohort: Placebo Participants diagnosed with IgAN will receive matched placebo in addition to standard-of-care background therapy.	Drug: Placebo Oral tablets

Contacts

Contact

Alexion Pharmaceuticals, Inc. (Sponsor)

1-855-752-2356

[email protected]