A Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy

• ClinicalTrials.gov Identifier: NCT04629248
• Recruitment Status: Recruiting
• First Posted: November 16, 2020
• Last Update Posted: January 11, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: October 27, 2020
• First Posted Date: November 16, 2020
• Last Update Posted Date: January 11, 2023
• Actual Study Start Date: June 25, 2021
• Estimated Primary Completion Date: January 9, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 9, 2020): Percentage of Participants who Achieve a Complete Remission (CR) at Week 104 [ Time Frame: Week 104 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 26, 2021)

• 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 [ Time Frame: Baseline to Week 104 ]
  Self-reported changes in fatigue will be measured using the PROMIS Fatigue Scale.
• 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to 8 years ]
  AESIs are required to be reported by the investigator to the Sponsor immediately
• 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 ]

Original Secondary Outcome Measures (submitted: November 9, 2020)

• 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 ]
• Percentage of Participants who Relapse by Week 104 [ Time Frame: Week 104 ]
• Percentage of Participants who Receive Escape Therapy by Week 104 [ Time Frame: Week 104 ]
• Percentage of Participants who Achieve Immunologic Remission at Week 52 [ Time Frame: Week 52 ]
• Mean Change in Ankle Circumference From Baseline to Week 104 [ Time Frame: Baseline (Day 1) to Week 104 ]
• Percentage of Participantswith >= 30% Reduction in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline (Day 1) to Week 104 ]
• Mean Change from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Assessment of Physical Health Scale at Week 104 [ Time Frame: Baseline (Day 1) to Week 104 ]
  Self-reported changes in physical health will be measured using the PROMIS Physical Health Scale.
• Mean Change from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Week 104 [ Time Frame: Baseline (Day 1) to Week 104 ]
  Self-reported changes in fatigue will be measured using the PROMIS Fatigue Scale.
• Duration of CR [ Time Frame: Up to 9 years ]
• Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 9 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) [ Time Frame: Up to 9 years ]
  AESIs are required to be reported by the investigator to the Sponsor immediately
• Peripheral B-cell Counts at Specified Timepoints [ Time Frame: Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 50, 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, 50, 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, 50, 52, 64, 76, 88, 104, 130, 156, 182, 208 and every 26 weeks thereafter ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy
• Official Title: A Phase III Randomized, Open-Label Active Comparator-Controlled Multicenter Study to Evaluate Efficacy and Safety of Obinutuzumab in Patients With Primary Membranous Nephropathy
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Primary Membranous Nephropathy

Intervention

• Drug: Obinutuzumab
  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.
  Other Name: Gazyva
• Drug: Tacrolimus
  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.
• Drug: Methylprednisolone
  Premedication: Methylprednisolone 80 mg IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.
• Drug: Acetaminophen
  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.
• Drug: Diphenhydramine
  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.

Study Arms

• Experimental: Open Label Treatment: Obinutuzumab
  Participants will be randomized at a 1:1 ratio to receive open-label treatment with obinutuzumab according to region and anti-phospholipase A2 receptor (PLA2R) autoantibody titer (using Euroimmun ELISA).
  Interventions:

  • Drug: Obinutuzumab
  • Drug: Methylprednisolone
  • Drug: Acetaminophen
  • Drug: Diphenhydramine
• Active Comparator: Open Label Treatment: Tacrolimus
  Participants will be randomized at a 1:1 ratio to receive open-label treatment with tacrolimus according to region and anti-PLA2R autoantibody titer (using Euroimmun ELISA).
  Intervention: Drug: Tacrolimus

• Publications *: Dossier C, Hogan J. Response to Majeranowski. Pediatr Nephrol. 2021 Jun;36(6):1653. doi: 10.1007/s00467-021-04982-4. Epub 2021 Mar 10. No abstract available.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 9, 2020): 140
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 1, 2028
• Estimated Primary Completion Date: January 9, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: WA41937 https://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); mailto:global-roche-genentech-trials@gene.com

• Listed Location Countries: Argentina, Brazil, China, France, Israel, Italy, Poland, Russian Federation, Spain, Turkey, Ukraine, United States
• Removed Location Countries: Peru

Administrative Information

• NCT Number: NCT04629248
• Other Study ID Numbers: WA41937; 2020-003233-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: January 2023