This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics (PK) of obinutuzumab compared with tacrolimus in participants with primary membranous nephropathy (pMN).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
142
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.
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.
Percentage of Participants who Achieve a Complete Remission (CR) at Week 104
Time frame: Week 104
Percentage of Participants who Achieve an Overall Remission at Week 104
Time frame: Week 104
Percentage of Participants who Achieve CR at Week 76
Time frame: Week 76
Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission
Time frame: Up to 8 years
Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline
Time frame: 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
Self-reported changes in fatigue will be measured using the PROMIS Fatigue Scale.
Time frame: Baseline to Week 104
Duration of CR
Time frame: Up to 8 years
Change in anti-PLA2R Autoantibody Titer
Time frame: Baseline to Week 52
Mean Change from Baseline in the PROMIS Global Assessment of Physical Health Scale at Week 104
Self-reported changes in physical health will be measured using the PROMIS Physical Health Scale
Time frame: Baseline to Week 104
Percentage of Participants with Adverse Events (AEs)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Premedication: Methylprednisolone 80 mg IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.
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.
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.
Kaiser Permanente - San Francisco Medical Center
San Francisco, California, United States
University of Colorado in Denver-Anschutz Medical Campus
Aurora, Colorado, United States
Accel Research Sites; Mid-Florida Kidney and Hypertension Care
Altamonte Springs, Florida, United States
University of Iowa
Iowa City, Iowa, United States
Henry Ford Hospital
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Columbia University Medical Center
New York, New York, United States
Nephrotex Research Group
Dallas, Texas, United States
Organizacion Medica de Investigacion
Buenos Aires, Argentina
CINME
Buenos Aires, Argentina
...and 40 more locations
Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Time frame: Up to 8 years
Percentage of Participants with AEs of Special Interest (AESIs)
AESIs are required to be reported by the investigator to the Sponsor immediately
Time frame: Up to 8 years
Peripheral B-cell Counts at Specified Timepoints
Time frame: 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
Time frame: 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
Time frame: Open Label: Baseline; Escape Treatment: Week 0
Incidence of ADAs during the study
Time frame: Weeks 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 130, 156, 182, 208 and every 26 weeks thereafter