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

July 3, 2026 updated by: Hoffmann-La Roche

A Phase III Randomized, Open-Label Active Comparator-Controlled Multicenter Study to Evaluate Efficacy and Safety of Obinutuzumab in Patients With Primary Membranous Nephropathy

This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics (PK) of obinutuzumab compared with tacrolimus in participants with primary membranous nephropathy (pMN).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

142

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1015ABO
        • Organizacion Medica de Investigacion
      • Buenos Aires, Argentina, C1056ABI
        • CINME
      • Buenos Aires, Argentina, C1280AEB
        • Hospital Britanico Buenos Aires
  • Brazil
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 40150-150
        • Ser Servicos Especializados Em Reumatologia
    • São Paulo
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Hospital de Base de Sao Jose do Rio Preto
      • São Paulo, São Paulo, Brazil, 05403-000
        • Hospital das Clinicas - FMUSP
      • São Paulo, São Paulo, Brazil, 04038-002
        • Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos
  • China
      • Beijing, China, 100034
        • Peking University First Hospital
      • Chengdu, China, 610072
        • Sichuan Provincial People's Hospital
      • Fuzhou, China, 350005
        • The 1st Affiliated hospital of Fujian Medical University
      • Guangzhou, China, 510515
        • Nanfang Hospital, Southern Medical University
      • Shanghai, China, 200040
        • Huashan Hospital, Fudan University
      • Shanghai, China, 200025
        • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
      • Wuhan, China, 430030
        • Tongji Hospital Tongji Medical College Huazhong University Of Science And Technology
      • Xi'an, China, 710061
        • The First Affiliated Hospital of Xian Jiao Tong University
      • Yinchuan, China, 750004
        • General Hospital of Ningxia Medical University
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310014
        • Zhejiang Provincial People?s Hospital
  • France
      • Créteil, France, 94010
        • Hopital Henri Mondor
      • Paris, France, 75020
        • Hôpital Tenon
      • Toulouse, France, 31059
        • Hopital Rangueil
  • Israel
      • Ramat Gan, Israel, 52621
        • Sheba MC
  • Italy
    • Apulia
      • Bari, Apulia, Italy, 70124
        • Policlinico di Bari
    • Campania
      • Naples, Campania, Italy, 80131
        • A.O. U. Federico II
    • Lombardy
      • Brescia, Lombardy, Italy, 25123
        • A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
      • Monza, Lombardy, Italy, 20900
        • ASST Monza - Ospedale San Gerardo
    • Piedmont
      • Turin, Piedmont, Italy, 10154
        • Ospedale San Giovanni Bosco
  • Poland
      • ?ód?, Poland, 90-153
        • Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego
      • ?ód?, Poland, 92-213
        • Uniwersytecki Szpital Kliniczny im WAM CSW
      • Bia?ystok, Poland, 15-276
        • Uniwersytecki Szpital Kliniczny w Bialymstoku
      • Bydgoszcz, Poland, 85-094
        • Szpital Uniwersytecki im.dr.A.Jurasza w Bydgoszczy
      • Wroc?aw, Poland, 50-556
        • Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
  • Russia
    • Moscow Oblast
      • Moscow, Moscow Oblast, Russia, 119021
        • First Moscow State Medical University n.a. I.M. Sechenov
    • Rostov Oblast
      • Rostov-on-Don, Rostov Oblast, Russia, 344022
        • Rostov State Medical Uni
    • Sankt-Peterburg
      • Saint Petersburg, Sankt-Peterburg, Russia, 196070
        • German clinic
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08036
        • Hospital Clinic I Provincial
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocío
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Hospital Universitari de Bellvitge
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 06100
        • Hacettepe Uni School of Medicine
      • Antalya, Turkey (Türkiye), 07059
        • Akdeniz University Medical Faculty
      • Izmir, Turkey (Türkiye), 35100
        • Ege Uni School of Medicine
  • United States
    • California
      • San Francisco, California, United States, 94118
        • Kaiser Permanente - San Francisco Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado in Denver-Anschutz Medical Campus
    • Florida
      • Altamonte Springs, Florida, United States, 32701
        • Accel Research Sites; Mid-Florida Kidney and Hypertension Care
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55902
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Texas
      • Dallas, Texas, United States, 75231
        • Nephrotex Research Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants who Achieve a Complete Remission (CR) at Week 104
Time Frame: Week 104
Week 104

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants who Achieve an Overall Remission at Week 104
Time Frame: Week 104
Week 104
Percentage of Participants who Achieve CR at Week 76
Time Frame: Week 76
Week 76
Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission
Time Frame: Up to 8 years
Up to 8 years
Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline
Time Frame: Up to 8 years
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.
Baseline to Week 104
Duration of CR
Time Frame: Up to 8 years
Up to 8 years
Change in anti-PLA2R Autoantibody Titer
Time Frame: Baseline to Week 52
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
Baseline to Week 104
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
Up to 8 years
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
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
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
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
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
Weeks 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 130, 156, 182, 208 and every 26 weeks thereafter

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 25, 2021

Primary Completion (Actual)

December 22, 2025

Study Completion (Estimated)

December 21, 2027

Study Registration Dates

First Submitted

October 27, 2020

First Submitted That Met QC Criteria

November 9, 2020

First Posted (Actual)

November 16, 2020

Study Record Updates

Last Update Posted (Actual)

July 7, 2026

Last Update Submitted That Met QC Criteria

July 3, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WA41937
  • 2020-003233-38 (EudraCT Number)
  • 2023-506525-11-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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