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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04629248
Recruitment Status : Recruiting
First Posted : November 16, 2020
Last Update Posted : August 18, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 27, 2020
First Posted Date  ICMJE November 16, 2020
Last Update Posted Date August 18, 2022
Actual Study Start Date  ICMJE June 25, 2021
Estimated Primary Completion Date January 9, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2020)
Percentage of Participants who Achieve a Complete Remission (CR) at Week 104 [ Time Frame: Week 104 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Primary Membranous Nephropathy
Intervention  ICMJE
  • 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  ICMJE
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 9, 2020)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2028
Estimated Primary Completion Date January 9, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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  ICMJE Argentina,   Brazil,   China,   France,   Israel,   Italy,   Poland,   Russian Federation,   Spain,   Turkey,   Ukraine,   United States
Removed Location Countries Peru
 
Administrative Information
NCT Number  ICMJE NCT04629248
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP