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

Phase 3

Active, not recruiting

• Conditions: Primary Membranous Nephropathy
• Interventions: Drug: Obinutuzumab; Drug: Tacrolimus; Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Diphenhydramine

• Registration Number: NCT04629248
• Lead Sponsor: Hoffmann-La Roche

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 available

Study Timeline

• Study First Submitted: 2020-10-27
• Study First Submitted QC: 2020-11-09
• Study First Posted: 2020-11-16
• Study Start: 2021-06-25
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-21
• Last Update Posted: 2025-03-24
• Primary Completion: 2025-12-29
• Study Completion: 2027-12-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 142

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Open Label Treatment: Obinutuzumab	Acetaminophen	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).
Open Label Treatment: Obinutuzumab	Diphenhydramine	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).
Open Label Treatment: Obinutuzumab	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).
Open Label Treatment: Tacrolimus	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).
Open Label Treatment: Obinutuzumab	Methylprednisolone	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).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants who Achieve a Complete Remission (CR) at Week 104	Week 104

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants who Achieve an Overall Remission at Week 104	Week 104
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	Self-reported changes in fatigue will be measured using the PROMIS Fatigue Scale.
Duration of CR	Up to 8 years
Mean Change from Baseline in the PROMIS Global Assessment of Physical Health Scale at Week 104	Baseline to Week 104	Self-reported changes in physical health will be measured using the PROMIS Physical Health Scale
Change in anti-PLA2R Autoantibody Titer	Baseline to Week 52
Percentage of Participants with AEs of Special Interest (AESIs)	Up to 8 years	AESIs are required to be reported by the investigator to the Sponsor immediately
Peripheral B-cell Counts at Specified Timepoints	Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 117, 130, 156, 182, 208 and every 26 weeks thereafter
Percentage of Participants with Adverse Events (AEs)	Up to 8 years	Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline	Up to 8 years
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
Serum Concentrations of Obinutuzumab at Specified Timepoints	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	Open Label: Baseline; Escape Treatment: Week 0
Incidence of ADAs during the study	Weeks 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 130, 156, 182, 208 and every 26 weeks thereafter

Trial Locations

Locations (50)

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili; 🇮🇹 Brescia, Lombardia, Italy

Hospital Britanico Buenos Aires; 🇦🇷 Buenos Aires, Argentina

Hopital Henri Mondor; 🇫🇷 Creteil, France

Hopital Tenon; 🇫🇷 Paris, France

Hopital Rangueil; 🇫🇷 Toulouse, France

Sheba MC; 🇮🇱 Ramat-Gan, Israel

A.O. U. Federico II; 🇮🇹 Napoli, Campania, Italy

Szpital Uniwersytecki im.dr.A.Jurasza w Bydgoszczy; 🇵🇱 Bydgoszcz, Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu; 🇵🇱 Wroc?aw, Poland

The First Affiliated Hospital of Xian Jiao Tong University; 🇨🇳 Xi'an City, China

General Hospital of Ningxia Medical University; 🇨🇳 Yinchuan, China

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Hospital das Clinicas - FMUSP; 🇧🇷 Sao Paulo, São Paulo, Brazil

ASST Monza - Ospedale San Gerardo; 🇮🇹 Monza, Lombardia, Italy

Ospedale San Giovanni Bosco; 🇮🇹 Torino, Piemonte, Italy

Policlinico di Bari; 🇮🇹 Bari, Puglia, Italy

Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego; 🇵🇱 ?ód?, Poland

Uniwersytecki Szpital Kliniczny im WAM CSW; 🇵🇱 ?ód?, Poland

Uniwersytecki Szpital Kliniczny w Bialymstoku; 🇵🇱 Bia?ystok, Poland

Rostov State Medical Uni; 🇷🇺 Rostov-na-donu, Rostov, Russian Federation

Hospital Universitari de Bellvitge; 🇪🇸 Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clinic i Provincial; 🇪🇸 Barcelona, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hacettepe Uni School of Medicine; 🇹🇷 Ankara, Turkey

Akdeniz University Medical Faculty; 🇹🇷 Antalya, Turkey

Ege Uni School of Medicine; 🇹🇷 Izmir, Turkey

Kaiser Permanente - San Francisco Medical Center; 🇺🇸 San Francisco, California, United States

University of Colorado in Denver-Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

Accel Research Sites; Mid-Florida Kidney and Hypertension Care; 🇺🇸 Altamonte Springs, Florida, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Nephrotex Research Group; 🇺🇸 Dallas, Texas, United States

Organizacion Medica de Investigacion; 🇦🇷 Buenos Aires, Argentina

CINME; 🇦🇷 Buenos Aires, Argentina

Ser Servicos Especializados Em Reumatologia; 🇧🇷 Salvador, Bahia, Brazil

Hospital de Base de Sao Jose do Rio Preto; 🇧🇷 Sao Jose do Rio Preto, São Paulo, Brazil

Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos; 🇧🇷 Sao Paulo, São Paulo, Brazil

Peking University First Hospital; 🇨🇳 Beijing City, China

Sichuan Provincial People's Hospital; 🇨🇳 Chengdu, China

The 1st Affiliated hospital of Fujian Medical University; 🇨🇳 Fuzhou City, China

Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, China

Zhejiang Provincial People?s Hospital; 🇨🇳 Hangzhou, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine; 🇨🇳 Shanghai City, China

Huashan Hospital, Fudan University; 🇨🇳 Shanghai City, China

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology; 🇨🇳 Wuhan City, China

First Moscow State Medical University n.a. I.M. Sechenov; 🇷🇺 Moscow, Moskovskaja Oblast, Russian Federation

German clinic; 🇷🇺 Sankt-peterburg, Sankt Petersburg, Russian Federation

Hospital Universitario Virgen del Rocío; 🇪🇸 Sevilla, Spain