Study of ALXN1920 in Adult Participants With Primary Membranous Nephropathy (PMN)

Recruitment & Eligibility

Inclusion Criteria

Participants who have a documented diagnosis of PMN, established by positive antiPLA2R antibody level (> 50 RU/mL) at Screening, which must be confirmed by a central laboratory
Participants are willing to receive the background Standard of Care (SoC)
Participants at high risk for disease progression, defined as:
1. Receiving ACE inhibitor or ARB for a minimum of 8 weeks prior to Screening, with the dose titrated to the maximally tolerated level. Participants with less than 8 weeks on ACE inhibitor or ARB before Screening or who have not yet reached maximally tolerated dose will enter the Run-in Period.
2. Participants who are on ACE inhibitor or ARB for a minimum of 8 weeks with Systolic Blood Pressure < 140 mmHg in ≥ 75% of the readings within last 8 weeks.
3. Having two proteinuria measurements with each > 3.5 g/day, the second measurement showing ≤50% decrease from the first measurement.
All participants must receive prophylactic treatment with appropriate antibiotics while receiving Rituximab (RTX), and be willing to be vaccinated against Neisseria meningitidis

Exclusion Criteria

Estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m^2 during Screening
Documented rapid deterioration of kidney function
History of life-threatening Nephrotic Syndrome within 1 year before Screening
Diagnosis of anti- phospholipase A2 receptor (PLA2R) negative membranous nephropathy (MN) or anti-PLA2R positive MN but Screening serum anti-PLA2R < 50 RU/mL or kidney disease other than PMN
History of kidney transplant or planned kidney transplant or dialysis during the Treatment Period
History of other solid organ (heart, lung, small bowel, pancreas, or liver) or bone marrow transplant; or planned transplant during the Treatment Period
History or presence of any clinically relevant co-morbidities
History of intolerance or hypersensitivity to ACEi or ARB
Use of SGLT2i, MRA, or ERA within 8 weeks prior to randomization and throughout the study period

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Study & Design

Arm && Interventions

Group	Intervention	Description
ALXN1920	ALXN1920	Participants will receive ALXN1920 subcutaneous (SC) and background treatment of ACE/ARB and Rituximab.
Placebo	Placebo	Participants will receive placebo subcutaneous (SC) and background treatment of ACE/ARB and Rituximab.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Proteinuria Based on 24-hour UPCR at Week 26	Baseline, Week 26

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Proteinuria Based on 24-hour UPCR	Baseline
Change From Baseline in Proteinuria Based on Spot UPCR at Week 26	Baseline and Week 26
Change From Baseline in Serum Albumin at Week 26	Baseline and Week 26
Change From Baseline in Anti-phospholipase A2 Receptor (anti-PLA2R) Antibody Level at Week 26	Baseline and 26
Change From Baseline in Peripheral Cluster of Differentiation 20 (CD20+) B Cell Count at Week 4, Week 8, and Week 26	Baseline, Weeks 4, 8 and 26
Change From Baseline biomarker level at Week 26	Baseline and Week 26

Recruitment & Eligibility