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

NCT ID: NCT04629248

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

142 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-25

Study Completion Date

2027-12-21

Brief Summary

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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

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Conditions

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Primary Membranous Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

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.

Methylprednisolone

Intervention Type DRUG

Premedication: Methylprednisolone 80 mg IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.

Acetaminophen

Intervention Type DRUG

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.

Diphenhydramine

Intervention Type DRUG

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.

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).

Group Type ACTIVE_COMPARATOR

Tacrolimus

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Methylprednisolone

Premedication: Methylprednisolone 80 mg IV will be administered between 30 and 60 minutes prior to the obinutuzumab infusion in all study periods.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Gazyva

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Kaiser Permanente - San Francisco Medical Center

San Francisco, California, United States

Site Status

University of Colorado in Denver-Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Accel Research Sites; Mid-Florida Kidney and Hypertension Care

Altamonte Springs, Florida, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Nephrotex Research Group

Dallas, Texas, United States

Site Status

Organizacion Medica de Investigacion

Buenos Aires, , Argentina

Site Status

CINME

Buenos Aires, , Argentina

Site Status

Hospital Britanico Buenos Aires

Buenos Aires, , Argentina

Site Status

Ser Servicos Especializados Em Reumatologia

Salvador, Estado de Bahia, Brazil

Site Status

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Site Status

Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos

São Paulo, São Paulo, Brazil

Site Status

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, Brazil

Site Status

Zhejiang Provincial People?s Hospital

Hangzhou, Zhejiang, China

Site Status

Peking University First Hospital

Beijing, , China

Site Status

Sichuan Provincial People's Hospital

Chengdu, , China

Site Status

The 1st Affiliated hospital of Fujian Medical University

Fuzhou, , China

Site Status

Nanfang Hospital, Southern Medical University

Guangzhou, , China

Site Status

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Site Status

Huashan Hospital, Fudan University

Shanghai, , China

Site Status

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

Site Status

The First Affiliated Hospital of Xian Jiao Tong University

Xi'an, , China

Site Status

General Hospital of Ningxia Medical University

Yinchuan, , China

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

Hopital Tenon

Paris, , France

Site Status

Hopital Rangueil

Toulouse, , France

Site Status

Sheba MC

Ramat Gan, , Israel

Site Status

Policlinico di Bari

Bari, Apulia, Italy

Site Status

A.O. U. Federico II

Napoli, Campania, Italy

Site Status

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili

Brescia, Lombardy, Italy

Site Status

ASST Monza - Ospedale San Gerardo

Monza, Lombardy, Italy

Site Status

Ospedale San Giovanni Bosco

Turin, Piedmont, Italy

Site Status

Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego

?ód?, , Poland

Site Status

Uniwersytecki Szpital Kliniczny im WAM CSW

?ód?, , Poland

Site Status

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bia?ystok, , Poland

Site Status

Szpital Uniwersytecki im.dr.A.Jurasza w Bydgoszczy

Bydgoszcz, , Poland

Site Status

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, , Poland

Site Status

First Moscow State Medical University n.a. I.M. Sechenov

Moscow, Moscow Oblast, Russia

Site Status

Rostov State Medical Uni

Rostov-on-Don, Rostov Oblast, Russia

Site Status

German clinic

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic i Provincial

Barcelona, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status

Hacettepe Uni School of Medicine

Ankara, , Turkey (Türkiye)

Site Status

Akdeniz University Medical Faculty

Antalya, , Turkey (Türkiye)

Site Status

Ege Uni School of Medicine

Izmir, , Turkey (Türkiye)

Site Status

Countries

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United States Argentina Brazil China France Israel Italy Poland Russia Spain Turkey (Türkiye)

References

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Dossier C, Bonneric S, Baudouin V, Kwon T, Prim B, Cambier A, Couderc A, Moreau C, Deschenes G, Hogan J. Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children. Clin J Am Soc Nephrol. 2023 Dec 1;18(12):1555-1562. doi: 10.2215/CJN.0000000000000288. Epub 2023 Sep 6.

Reference Type DERIVED
PMID: 37678236 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33693991 (View on PubMed)

Other Identifiers

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2020-003233-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506525-11-00

Identifier Type: OTHER

Identifier Source: secondary_id

WA41937

Identifier Type: -

Identifier Source: org_study_id

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