Primary Membranous Nephropathy
Conditions
Keywords
Primary Membranous Nephropathy, PMN, ALXN1920
Brief summary
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).
Interventions
DRUGALXN1920
Participants will receive ALXN1920 SC infusion.
DRUGPlacebo
Participants will receive Placebo SC infusion.
Sponsors
Alexion Pharmaceuticals, Inc.
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Proteinuria Based on 24-hour UPCR at Week 26 | Baseline, Week 26 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Proteinuria Based on 24-hour UPCR at week 12 | Baseline and week 12 |
| Change From Baseline in Proteinuria Based on Spot UPCR at Week 12 and week 26 | Baseline, Week 12 and Week 26 |
| Change From Baseline in Serum Albumin at Week 12 and week 26 | Baseline, week 12 and Week 26 |
| Change From Baseline in Anti-phospholipase A2 Receptor (anti-PLA2R) Antibody Level at Week 12 and week 26 | Baseline, week 12 and week 26 |
| Change From Baseline in Peripheral CD19+ B Cell Count at Week 4, Week 8, Week 12 and Week 26 | Baseline, Weeks 4, 8, 12 and 26 |
| Change From Baseline biomarker level at Week 12 and 26 | Baseline and Weeks 12 and 26 |
Countries
Argentina, Australia, Brazil, China, France, Italy, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTAlexion Pharmaceuticals, Inc. (Sponsor)
Outcome results
None listed