ALXN1920 for Primary membranous nephropathy

Inclusion criteria

• {"criterion_text":"-Participant must be ≥18 and ≤75 years of age at the time of signing the informed consent.\n-Participants who have a documented diagnosis of PMN, established by positive anti PLA2R antibody level (>50 RU/mL) at Screening, which must be confirmed by a central laboratory.\n-Participants at high risk for disease progression, defined as: a. Receiving ACE inhibitors or ARB for a minimum of 8 weeks prior to Screening, with the dose titrated to the maximally tolerated level; however, participants with less than 8 weeks on ACE or ARB before Screening or who have not yet reached maximally tolerated dose will enter the Run-in Period for up to 8 weeks, b. Participants who are on ACE inhibitors or ARB for a minimum of 8 weeks with SBP < 140 mmHg in ≥ 75% of the readings (within the last 8 weeks) are allowed to be randomized, and c. Having two proteinuria measurements by either a 24-hour urine collection or a spot urine with each > 3.5 g/day, the second measurement showing ≤50% decrease from the first measurement.\n-Male or female assigned at birth, inclusive of all gender identities.\n-Agree to follow protocol-specified contraception guidance.\n-Signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.\n-Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative.\n-Participants are willing to receive the background SoC.\n-To reduce the risk of infections, all participants must receive prophylactic treatment with appropriate antibiotics while receiving RTX and be willing to be vaccinated against Neisseria meningitidis."}

Exclusion criteria

• {"criterion_text":"-eGFR <60 mL/min/1.73 m2 during Screening calculated by CKD-EPI\n-History of malignancy within 5 years prior to Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.\n-History of hypersensitivity to any ingredient contained in the study intervention, including inability to take or tolerate the allowed concomitant therapies.\n-Documented rapid deterioration of kidney function (20% or greater decline in eGFR sustained over a period of at least 3 months within 24 months before Screening)\n-Participants with BMI > 40.\n-Uncontrolled HTN, defined as BP ≥ 140 mm Hg systolic and/or ≥ 90 mm Hg diastolic on ≥3 BP medications.\n-Laboratory abnormalities at Screening, including: • ALT > 2 × ULN • Direct bilirubin > 2 × ULN • HbA1c at Screening > 6.5%\n-Any other clinically significant laboratory abnormality that, in the opinion of the Investigator, would make the participant inappropriate for the study or put the participant at undue risk.\n-A history of Diabetes Mellitus Type 1 and diagnosis of Diabetes Mellitus Type 2.\n-Current treatment with a biologic medication that may affect immune system functioning or previous treatment with a biologic medication that may affect immune system functioning stopped within 30 days or 5 terminal half-lives of the biologic medication, whichever is longer, prior to Screening Visit.\n-Any previous or current treatment with complement inhibitors (including but not limited to, eculizumab, ravulizumab).\n-Presence of hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) at screening or within 3 months. NOTE: Participants with known positive HBsAb may be randomized provided they are hepatitis B-vaccinated and have negative HBsAg and HBcAb.\n-Anti-CD20 antibody use within 6 months prior to Screening.\n-Participants who are receiving or have received obinutuzumab.\n-Cyclophosphamide use within 6 months prior to Screening.\n-History of life-threatening Nephrotic Syndrome (serum albumin <2.5 g/dL AND either treatment refractory edema or thromboembolic event) within 1 year before Screening.\n-Immunosuppressants other than anti-CD20 antibody or cyclophosphamide used within 12 weeks prior to Screening.\n-Participants who are unable to take at least 1 antimicrobial agent used to prevent N meningitidis.\n-Participation in another investigational drug or investigational device study within 30 days before initiation of study intervention on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.\n-Pregnant, breastfeeding, or intending to conceive during the course of the study.\n-History of resistance to RTX defined as one of the following: • having a reduction in proteinuria of <25% after 6 months of treatment with RTX (including any increase in proteinuria), or, • reduction in anti-PLA2R antibody levels < 25% at 3 months, or < 50% at 6 months, after treatment with RTX Note: Participants who previously responded to RTX with either a CR or PR but relapsed at least 6 months after last RTX dose are eligible (relapse is defined as a return of proteinuria to > 3.5 g/day after an initial CR or PR to immunosuppressive therapy\n-History of intolerance or hypersensitivity to ACEi or ARB, including but not limited to angioedema, persistent cough, or clinically significant hypotension attributed to these agents.\n-Positive hepatitis C antibody test result at screening or within 3 months unless HCV RNA negative test is documented.\n-Use of SGLT2i, MRA, or ERA within 8 weeks prior to randomization and throughout the study period.\n-Diagnosis of anti-PLA2R negative MN or anti-PLA2R positive MN but Screening serum anti-PLA2R < 50 RU/mL or kidney disease other than PMN.\n-History of kidney transplant or planned kidney transplant or dialysis during the Treatment Period.\n-History of other solid organ (heart, lung, small bowel, pancreas, or liver) or bone marrow transplant; or planned transplant during the Treatment Period.\n-Splenectomy or functional asplenia.\n-Known or suspected complement deficiency, unless attributable to underlying disease.\n-Positive COVID-19 test at Screening.\n-Participants with active or latent tuberculosis.\n-Hereditary (primary) hypogammaglobulinemia (as confirmed by medical history), including but not limited to X-linked agammaglobulinemia, CVID, or other diagnosed primary immunodeficiency disorders associated with significantly reduced immunoglobulin levels.\n-Participants with history of HIV who are not on anti-retroviral therapy or if on therapy have a known detectable viral load within 1 year of Screening.\n-Known medical or psychological condition(s), including substance abuse, or risk factor that, in the opinion of the Investigator, might interfere with the participant’s full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study.\n-History of any Neisseria infection.\n-History of unexplained, recurrent infection, or infection requiring treatment with systemic antibiotics within 90 days prior to Day 1.\n-Active systemic bacterial, viral, or fungal infection within 14 days prior to first dose of study intervention.\n-QTc > 480 msec in participants with bundle branch block."}

Primary endpoints

• {"endpoint_text":"-Change from Baseline in proteinuria based on 24-hour UPCR","definition_or_measurement_approach":"Measured as change from baseline in 24-hour urine protein-to-creatinine ratio (24-hour UPCR) as specified in the main objective."}

Secondary endpoints

• {"endpoint_text":"-Change from Baseline in proteinuria based on 24-hour UPCR","definition_or_measurement_approach":"Change from baseline measured using 24-hour UPCR."}
• {"endpoint_text":"-Change from Baseline in proteinuria based on spot UPCR","definition_or_measurement_approach":"Change from baseline measured using spot urine protein-to-creatinine ratio (spot UPCR)."}
• {"endpoint_text":"-Change from Baseline in serum albumin","definition_or_measurement_approach":"Change from baseline in serum albumin concentration measured by standard clinical laboratory assays."}
• {"endpoint_text":"-Change from Baseline in anti-PLA2R antibody level","definition_or_measurement_approach":"Change from baseline in circulating anti-PLA2R antibody levels measured by central laboratory assay."}
• {"endpoint_text":"-Change from Baseline in Peripheral CD20+ B cell count","definition_or_measurement_approach":"Change from baseline in peripheral blood CD20+ B cell counts measured by flow cytometry."}
• {"endpoint_text":"-Change from Baseline for urine biomarkers","definition_or_measurement_approach":"Change from baseline in predefined urine biomarkers (details per protocol laboratory methods)."}
• {"endpoint_text":"-Change from Baseline for urine biomarkers","definition_or_measurement_approach":"Change from baseline in predefined urine biomarkers (duplicate listing in source)."}
• {"endpoint_text":"-Incidence of TEAEs and TESAEs over time","definition_or_measurement_approach":"Incidence and timing of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) collected throughout the study."}
• {"endpoint_text":"-Change from Baseline in safety parameters, vital signs, ECGs over time","definition_or_measurement_approach":"Change from baseline in standard safety laboratory parameters, vital signs and ECG findings measured at protocol-defined timepoints."}
• {"endpoint_text":"-Serum and urine ALXN1920 concentrations over time","definition_or_measurement_approach":"Pharmacokinetic measurements of ALXN1920 concentrations in serum and urine at specified timepoints."}
• {"endpoint_text":"-Absolute values, change from Baseline, and percent change from Baseline in serum CAP activity and serum fH levels over time","definition_or_measurement_approach":"Laboratory measurement of serum complement alternative pathway (CAP) activity and factor H (fH) levels: absolute values and changes from baseline over time."}
• {"endpoint_text":"-ADA incidence, category of immune response, and titer through the duration of the study","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADA): incidence, immune response category and titers measured during the study."}

Italy

Earliest CTIS Part Ii Submission Date

11-08-2025

Latest Decision Or Authorization Date

21-11-2025

Processing Time Days

102

Number Of Sites

3

Number Of Participants

3

France

Earliest CTIS Part Ii Submission Date

27-10-2025

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

91

Number Of Sites

3

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

29-10-2025

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

83

Number Of Sites

4

Number Of Participants

4

Primary sponsor

Full Name

Alexion Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States