Primary Membranous Nephropathy
Conditions
Keywords
BGB-3111, Zanubrutinib, BTKi
Brief summary
The primary objectives of this study are: In Part 1 to evaluate the efficacy of zanubrutinib as measured by proteinuria reduction, and in Part 2 to evaluate the efficacy of zanubrutinib compared with tacrolimus as measured by complete remission rate, in participants with primary membranous nephropathy (PMN) who are on optimal supportive care.
Detailed description
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGZanubrutinib
Zanubrutinib capsules administered orally.
DRUGTacrolimus
Tacrolimus capsules administered orally.
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In Part I, participants will be assigned to one treatment group. After enrollment in Part I is complete, enrollment in Part 2 will start. In Part 2, participants will be randomly assigned to 1 of 3 treatment groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Biopsy-confirmed PMN within 5 years before the initial screening (ie, the day the informed consent is signed) * UPCR (based on 24-hour urine collection) \> 3.5 at initial screening and at confirmation assessment * Treatment with a maximally tolerated or allowed dose of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) for ≥ 24 weeks before randomization (12 weeks before initiation of study drug for Part 1) and with adequate blood pressure control (blood pressure \< 130/80 mmHg, measured on ≥ 2 occasions \[not on the same day\] within 4 weeks before the assignment of study treatment) * Anti-PLA2R antibody \> 50 RU/mL at confirmation assessment (Part 1 only)
Exclusion criteria
* Participants with a secondary cause of membranous nephropathy * Type 1 or 2 diabetes mellitus with hemoglobin A1c (HbA1c) ≥ 7% at screening * Severe renal disease as determined by rapid decline in eGFR (defined as \> 15 mL/min/1.73m\^2 within 24 weeks prior to randomization, not otherwise explained) * A known history of a primary immunodeficiency or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infections * Patients at risk for tuberculosis at screening * Known infection with serologic status reflecting active or chronic hepatitis B virus infection, or presence of hepatitis C virus antibody * Severe hepatic insufficiency (Child-Pugh C) * Clinically significant cardio-cerebrovascular diseases Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR) | Baseline and Week 24 | — |
| Part 2: Number of Participants Achieving Complete Remission | Week 104 | Complete remission is defined as: UPCR (based on 24-hour urine collection) ≤ 0.3, AND a stable estimated glomerular filtration rate (eGFR) (remains unchanged or decreases by \< 15% compared with the baseline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of participants with Treatment Failure | Week 24 | — |
| Part 1: Number of Participants with Immunological Response | Week 24 | Immunological response is defined as anti- phospholipase A2 receptor (PLA2R) antibody level reduced from baseline to less than 14 relative units (RU)/ml. |
| Part 1: Number of Participants with Complete Remission | Week 24, Week 52, Week 76, and Week 104 | A complete remission is defined as: UPCR (based on 24-hour urine collection) ≤ 0.3, AND a stable eGFR (remains unchanged or decreases by \< 15% compared with the baseline) |
| Part 1: Number of Participants with Overall Remission | Week 24, Week 52, Week 76, and Week 104 | Participants with overall remission are those achieving either complete remission or partial remission |
| Part 1: Number of Participants with Relapse | Week 104 | A relapse is defined as reappearance of UPCR (based on 24-hour urine collection) \> 3.5 after complete or partial remission |
| Part 1: Number Of Participants with Treatment-Emergent Adverse Events (TEAEs) | From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks | — |
| Part 2: Number of Participants with Overall Remission | Week 24, Week 52, Week 76, and Week 104 | Participants with overall remission are those achieving either complete remission or partial remission |
| Part 2: Number of Participants with Complete Remission | Week 24, Week 52, and Week 76 | A complete remission is defined as: UPCR (based on 24-hour urine collection) ≤ 0.3, AND a stable eGFR (remains unchanged or decreases by \< 15% compared with the baseline) |
| Part 2: Number of participants with Treatment Failure | Week 24, Week 52, Week 76, and Week 104 | — |
| Part 2: Time to First Complete Remission | Up to approximately 104 weeks | Time to First Complete Remission is the time from the date of randomization to the date of the first complete remission |
| Part 2: Time to First Overall Remission | Up to approximately 104 weeks | Time to first overall remission is the time from the date of randomization to the date of the first overall remission |
| Part 2: Number of Participants with Relapse | Week 104 | A relapse is defined as reappearance of UPCR (based on 24-hour urine collection) \> 3.5 after complete or partial remission |
| Part 2: Time to First Relapse | Up to approximately 104 weeks | Time to first relapse is the time from the date of first complete or partial remission to the date of the first relapse |
| Part 2: Health Related quality of Life (HRQoL) Using the Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36) | Up to approximately 104 weeks | — |
| Part 2: Health Related quality of Life (HRQoL) Using European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L) | Up to approximately 104 weeks | — |
| Number of Participants with ≥ 30% Estimated Glomerular Filtration Rate (eGFR) Reduction from Baseline | Baseline, Week 52, and Week 104 | — |
| Part 2: Number of Participants with TEAEs | From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks | — |
Countries
Brazil, Canada, China, Czechia, Italy, Russia, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed