Primary Membranous Nephropathy
Conditions
Brief summary
This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics (PK) of obinutuzumab compared with tacrolimus in participants with primary membranous nephropathy (pMN).
Interventions
DRUGObinutuzumab
Open Label: An intravenous (IV) infusion of 1000 milligram (mg) of obinutuzumab will be administered at Week 0, Week 2, Week 24, and Week 26. Participants who relapse during the open-label treatment period may be eligible for further treatment.
DRUGTacrolimus
Open Label: Participants will receive tacrolimus at a starting oral dose (PO) of 0.05 mg/kilogram (kg) (participant dry weight) per day divided into two equal doses given at 12-hour intervals, titrated to serum trough level 5-7 Nanograms per millilitre (ng/mL). Optimized tacrolimus dose will be maintained for a maximum 52 weeks dependent on response and then tapered over 8 weeks. Participants who relapse during the open-label treatment period will have their dose of tacrolimus tapered over 8 weeks and may be eligible for further treatment.
DRUGMethylprednisolone
Premedication: Methylprednisolone 80 mg IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.
DRUGAcetaminophen
Premedication: Acetaminophen (650-1000 mg, or equivalent dose of a similar agent) PO or IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.
DRUGDiphenhydramine
Premedication: Diphenhydramine (50 mg, or equivalent dose of a similar agent) PO or IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of primary membranous nephropathy (pMN) according to renal biopsy prior to or during screening * Screening urinary protein-to-creatinine ratio (UPCR) \>= 5 g/g from 24-hour urine collection after best supportive care for \>= 3 months prior to screening or screening UPCR \>= 4 g/g after best supportive care for \>= 6 months prior to screening * eGFR \>= 40 mL/min/1.73m\^2 or qualified endogenous creatinine clearance \>= 40 mL/min/1.73m\^2 based on 24-hour urine collection during screening * Other inclusion criteria may apply
Exclusion criteria
* Participants with a secondary cause of MN * Pregnancy or breastfeeding * Evidence of \>= 50% reduction in proteinuria during the previous 6 months prior to randomization * Severe renal impairment, including the need for dialysis or renal replacement therapy * Type 1 or 2 diabetes mellitus * Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to or during screening; or cyclophosphamide, tacrolimus, or cyclosporin less than 6 months prior to or during screening * Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude participant participation * Known active infection of any kind or recent major episode of infection * Major surgery requiring hospitalization within the 4 weeks prior to screening * Current active alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening * Intolerance or contraindication to study therapies * Other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants who Achieve a Complete Remission (CR) at Week 104 | Week 104 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Achieve an Overall Remission at Week 104 | Week 104 | — |
| Percentage of Participants who Achieve CR at Week 76 | Week 76 | — |
| Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission | Up to 8 years | — |
| Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline | Up to 8 years | — |
| Mean Change in T-score from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Week 104 | Baseline to Week 104 | Self-reported changes in fatigue will be measured using the PROMIS Fatigue Scale. |
| Duration of CR | Up to 8 years | — |
| Change in anti-PLA2R Autoantibody Titer | Baseline to Week 52 | — |
| Mean Change from Baseline in the PROMIS Global Assessment of Physical Health Scale at Week 104 | Baseline to Week 104 | Self-reported changes in physical health will be measured using the PROMIS Physical Health Scale |
| Percentage of Participants with Adverse Events (AEs) | Up to 8 years | Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 |
| Percentage of Participants with AEs of Special Interest (AESIs) | Up to 8 years | AESIs are required to be reported by the investigator to the Sponsor immediately |
| Peripheral B-cell Counts at Specified Timepoints | Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 117, 130, 156, 182, 208 and every 26 weeks thereafter | — |
| Serum Concentrations of Obinutuzumab at Specified Timepoints | Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 117, 130, 143, 156, 169, 182, 195, 208, every 26 weeks thereafter | — |
| Prevalence of Anti-drug Antibodies (ADAs) to Obinutuzumab at Baseline | Open Label: Baseline; Escape Treatment: Week 0 | — |
| Incidence of ADAs during the study | Weeks 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 130, 156, 182, 208 and every 26 weeks thereafter | — |
Countries
Argentina, Brazil, China, France, Israel, Italy, Poland, Russia, Spain, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed