Primary Membranous Nephropathy
Conditions
Keywords
PMN, Anti-CD19, PrisMN
Brief summary
To evaluate the safety and tolerability of three dose regimens of budoprutug in subjects with PMN
Detailed description
Budoprutug is a humanized, immunoglobulin (Ig) G1 monoclonal antibody that selectively binds to CD19 and is projected to deplete targeted cells through antibody-dependent cellular cytotoxicity (ADCC). This Phase 2, open-label, multicenter study evaluates the safety, pharmacodynamics, and preliminary efficacy of three intravenous dose regimens of budoprutug in adult subjects with primary membranous nephropathy (PMN) who are anti-PLA2R antibody positive and have persistent proteinuria despite optimized RAAS inhibition. Approximately 45 subjects will be enrolled across three sequential dose cohorts, each receiving a single IV dose of budoprutug on Day 1, Day 15, Day 169 and Day 183. Subjects will be followed through Week 48, with extended follow-up for B-cell recovery as needed.
Interventions
DRUGbudoprutug
Single IV dose of study product on Day 1, Day 15, Day 169 and Day 183
Sponsors
Climb Bio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of PMN with positive anti-PLA2R antibodies * CD19+ B cell count ≥40 cells/μL * UPCR ≥2.0 g/g * eGFR ≥35 mL/min/1.73 m² * Stable RAAS inhibitor therapy * Blood pressure \<150/90 mmHg at baseline * Adequate hematologic, hepatic, and renal function * Willing to use effective contraception (both sexes) * Other inclusion criteria may apply
Exclusion criteria
* Secondary Membranous Nephropathy * Rapidly progressive glomerulonephritis or other glomerulopathies * Prior B cell-depleting therapy within 24 weeks * Recent use of immunosuppressants * Active or high-risk infections * History of malignancy * Pregnancy or breastfeeding * Recent major surgery or hospitalization * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Up to Week 48 | Number of participants experiencing TEAEs, graded per NCI CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in total B Cell Count | Up to Week 48 | Absolute and % change in total number of peripheral B cells over time. |
| Change in Anti-PLA2R Antibodies | Up to Week 48 | Change from Baseline in anti-PLA2R antibody titers over time. |
| Complete Remission Rate | Week 48 | Proportion of subjects who achieve complete remission at Week 48. |
| Complete or Partial Remission Rate | Week 48 | Proportion of subjects who achieve complete or partial remission at Week 48. |
| Change in Proteinuria | Up to Week 48 | Change from Baseline in proteinuria (measured via urine protein-creatinine ratio, UPCR) over time. |
| Change in UACR | Up to Week 48 | Change in urine albumin-to-creatinine ratio over time. |
| Change in eGFR | Up to Week 48 | Change from Baseline in eGFR over time. |
| Area Under the Curve (AUC) | Up to Week 48 | Measurement of the area under the drug concentration-time curve. |
| Maximum Observed Plasma Concentration (Cmax) | Up to Week 48 | Measurement of the maximum observed plasma concentration. |
| Time to Maximum Observed Concentration (Tmax) | Up to Week 48 | Measurement of the time to maximum observed concentration. |
| Terminal Half-Life (T1/2) | Up to Week 48 | Measurement of the terminal half-life in days. |
| Apparent Clearance (CL/F) | Up to Week 48 | Measurement of the apparent clearance in L/hour. |
| Volume of Distribution (Vd) | Up to Week 48 | Measurement of the volume of distribution in liters. |
Countries
Argentina, Brazil, Chile, China, Georgia, Taiwan, Ukraine, United States
Contacts
CONTACTClimb Bio Study Director
Outcome results
None listed