The primary objective of this study is to evaluate the efficacy of ALXN1920 compared with placebo in participants with PMN who are at a high risk for disease progression using 24-hour urine protein creatinine ratio (UPCR).

Inclusion Criteria:

• Participants who have a documented diagnosis of PMN, established by positive antiPLA2R antibody level (> 20 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.

• eGFR60 mL/min/1.73 m2 during Screening calculated by CKD-EPI 2021 creatinine formula

• All participants must receive prophylactic treatment with appropriate antibiotics while receiving Rituximab (RTX), and be willing to be vaccinated against Neisseria meningitidis

Exclusion Criteria:

• 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 < 20 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
• Initiation or dose adjustment of SGLT2i within 12 weeks prior to randomization or planned adjustment of GSLT2i dose throughout the treatment period.
• Use of traditional Chinese medicines or Chinese proprietary medicines with systemic immunosuppressive properties within 6 months prior to screening.
• Use of MRA, or ERA within 12 weeks prior to randomization and throughout the study period

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

Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.