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

NCT04629248 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: WA419372020-003233-382023-506525-11-00
• Study Type: interventional
• Target: 142
• Locations: 11 countries
• Sites: 50

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).

Conditions

Primary Membranous Nephropathy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants who Achieve a Complete Remission (CR) at Week 104

  Week 104

Secondary Outcomes (14)

• Percentage of Participants who Achieve an Overall Remission at Week 104

  Week 104

• Percentage of Participants who Achieve CR at Week 76

  Week 76

• Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission

  Up to 8 years

• Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline

  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

  Baseline to Week 104

Study Arms (2)

Open Label Treatment: Obinutuzumab

EXPERIMENTAL

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; Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Diphenhydramine

Open Label Treatment: Tacrolimus

ACTIVE COMPARATOR

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

Interventions

Obinutuzumab 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.

Also known as: Gazyva

Open Label Treatment: Obinutuzumab

Tacrolimus 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.

Open Label Treatment: Tacrolimus

Methylprednisolone DRUG

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

Open Label Treatment: Obinutuzumab

Acetaminophen 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.

Open Label Treatment: Obinutuzumab

Diphenhydramine 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: Obinutuzumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (50)

Kaiser Permanente - San Francisco Medical Center

San Francisco, California, 94118, United States

Location

University of Colorado in Denver-Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Accel Research Sites; Mid-Florida Kidney and Hypertension Care

Altamonte Springs, Florida, 32701, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Nephrotex Research Group

Dallas, Texas, 75231, United States

Location

Organizacion Medica de Investigacion

Buenos Aires, C1015ABO, Argentina

Location

CINME

Buenos Aires, C1056ABI, Argentina

Location

Hospital Britanico Buenos Aires

Buenos Aires, C1280AEB, Argentina

Location

Ser Servicos Especializados Em Reumatologia

Salvador, Estado de Bahia, 40150-150, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos

São Paulo, São Paulo, 04038-002, Brazil

Location

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, 05403-000, Brazil

Location

Zhejiang Provincial People?s Hospital

Hangzhou, Zhejiang, 310014, China

Location

Peking University First Hospital

Beijing, 100034, China

Location

Sichuan Provincial People's Hospital

Chengdu, 610072, China

Location

The 1st Affiliated hospital of Fujian Medical University

Fuzhou, 350005, China

Location

Nanfang Hospital, Southern Medical University

Guangzhou, 510515, China

Location

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, 200025, China

Location

Huashan Hospital, Fudan University

Shanghai, 200040, China

Location

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430030, China

Location

The First Affiliated Hospital of Xian Jiao Tong University

Xi'an, 710061, China

Location

General Hospital of Ningxia Medical University

Yinchuan, 750004, China

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital Tenon

Paris, 75020, France

Location

Hopital Rangueil

Toulouse, 31059, France

Location

Sheba MC

Ramat Gan, 52621, Israel

Location

Policlinico di Bari

Bari, Apulia, 70124, Italy

Location

A.O. U. Federico II

Naples, Campania, 80131, Italy

Location

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

Brescia, Lombardy, 25123, Italy

Location

ASST Monza - Ospedale San Gerardo

Monza, Lombardy, 20900, Italy

Location

Ospedale San Giovanni Bosco

Turin, Piedmont, 10154, Italy

Location

Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego

?ód?, 90-153, Poland

Location

Uniwersytecki Szpital Kliniczny im WAM CSW

?ód?, 92-213, Poland

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bia?ystok, 15-276, Poland

Location

Szpital Uniwersytecki im.dr.A.Jurasza w Bydgoszczy

Bydgoszcz, 85-094, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, 50-556, Poland

Location

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

Moscow, Moscow Oblast, 119021, Russia

Location

Rostov State Medical Uni

Rostov-on-Don, Rostov Oblast, 344022, Russia

Location

German clinic

Saint Petersburg, Sankt-Peterburg, 196070, Russia

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hacettepe Uni School of Medicine

Ankara, 06100, Turkey (Türkiye)

Location

Akdeniz University Medical Faculty

Antalya, 07059, Turkey (Türkiye)

Location

Ege Uni School of Medicine

Izmir, 35100, Turkey (Türkiye)

Location

Related Publications (2)

• 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.

  PMID: 37678236 DERIVED

• 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.

  PMID: 33693991 DERIVED

MeSH Terms

Interventions

obinutuzumab; Tacrolimus; Methylprednisolone; Acetaminophen; Diphenhydramine

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: November 16, 2020
• Study Start: June 25, 2021
• Primary Completion: December 22, 2025
• Study Completion (Estimated): December 21, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

PL (5); IL (1); US (8); FR (3); ES (5); TU (3); RU (3); AR (3); BR (4); CN (10); IT (5)