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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 : May 11, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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).

Condition or disease Intervention/treatment Phase
Primary Membranous Nephropathy Drug: Obinutuzumab Drug: Tacrolimus Drug: Methylprednisolone Drug: Acetaminophen Drug: Diphenhydramine Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 25, 2021
Estimated Primary Completion Date : January 9, 2025
Estimated Study Completion Date : June 1, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arms and Interventions
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Arm Intervention/treatment
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).
 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: 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.
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).
 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.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants who Achieve a Complete Remission (CR) at Week 104 [ Time Frame: Week 104 ]

Secondary Outcome Measures :
  1. Percentage of Participants who Achieve an Overall Remission at Week 104 [ Time Frame: Week 104 ]
  2. Percentage of Participants who Achieve CR at Week 76 [ Time Frame: Week 76 ]
  3. Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission [ Time Frame: Up to 8 years ]
  4. Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline [ Time Frame: Up to 8 years ]
  5. 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.

  6. Duration of CR [ Time Frame: Up to 8 years ]
  7. Change in anti-PLA2R Autoantibody Titer [ Time Frame: Baseline to Week 52 ]
  8. 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

  9. 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

  10. 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

  11. 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 ]
  12. 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 ]
  13. Prevalence of Anti-drug Antibodies (ADAs) to Obinutuzumab at Baseline [ Time Frame: Open Label: Baseline; Escape Treatment: Week 0 ]
  14. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04629248


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

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04629248    
Other Study ID Numbers: WA41937
2020-003233-38 ( EudraCT Number )
First Posted: November 16, 2020    Key Record Dates
Last Update Posted: May 11, 2023
Last Verified: May 2023
Individual Participant Data (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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Glomerulonephritis, Membranous
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
Acetaminophen
Diphenhydramine
Promethazine
Methylprednisolone
 Obinutuzumab
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antipyretics
Anti-Inflammatory Agents
Antiemetics