Clinical trial NCT04629248: A Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Primary Membranous Nephropathy
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-11-16
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Percentage of Participants who Achieve a Complete Remission (CR) at Week 104
timeFrame: Week 104
Secondary outcomes:
measure: Percentage of Participants who Achieve an Overall Remission at Week 104
timeFrame: Week 104
measure: Percentage of Participants who Achieve CR at Week 76
timeFrame: Week 76
measure: Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission
timeFrame: Up to 8 years
measure: Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline
timeFrame: Up to 8 years
measure: Mean Change in T-score from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Week 104
timeFrame: Baseline to Week 104
measure: Duration of CR
timeFrame: Up to 8 years
measure: Change in anti-PLA2R Autoantibody Titer
timeFrame: Baseline to Week 52
measure: Mean Change from Baseline in the PROMIS Global Assessment of Physical Health Scale at Week 104
timeFrame: Baseline to Week 104
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 8 years
measure: Percentage of Participants with AEs of Special Interest (AESIs)
timeFrame: Up to 8 years
measure: Peripheral B-cell Counts at Specified Timepoints
timeFrame: Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 117, 130, 156, 182, 208 and every 26 weeks thereafter
measure: Serum Concentrations of Obinutuzumab at Specified Timepoints
timeFrame: 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
measure: Prevalence of Anti-drug Antibodies (ADAs) to Obinutuzumab at Baseline
timeFrame: Open Label: Baseline; Escape Treatment: Week 0
measure: Incidence of ADAs during the study
timeFrame: Weeks 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 130, 156, 182, 208 and every 26 weeks thereafter
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Kaiser Permanente - San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado in Denver-Anschutz Medical Campus
state: Colorado
city: Altamonte Springs
country: United States
facility: Accel Research Sites; Mid-Florida Kidney and Hypertension Care
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Dallas
country: United States
facility: Nephrotex Research Group
state: Texas
city: Buenos Aires
country: Argentina
facility: Organizacion Medica de Investigacion
city: Buenos Aires
country: Argentina
facility: CINME
city: Buenos Aires
country: Argentina
facility: Hospital Britanico Buenos Aires
city: Salvador
country: Brazil
facility: Ser Servicos Especializados Em Reumatologia
state: Bahia
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas - FMUSP
state: São Paulo
city: Beijing City
country: China
facility: Peking University First Hospital
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Fuzhou City
country: China
facility: The 1st Affiliated hospital of Fujian Medical University
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Hangzhou
country: China
facility: Zhejiang Provincial People?s Hospital
city: Shanghai City
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Shanghai City
country: China
facility: Huashan Hospital, Fudan University
city: Wuhan City
country: China
facility: Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xi'an City
country: China
facility: The First Affiliated Hospital of Xian Jiao Tong University
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Paris
country: France
facility: Hopital Tenon
city: Toulouse
country: France
facility: Hopital Rangueil
city: Ramat-Gan
country: Israel
facility: Sheba MC
city: Napoli
country: Italy
facility: A.O. U. Federico II
state: Campania
city: Brescia
country: Italy
facility: A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
state: Lombardia
city: Monza
country: Italy
facility: ASST Monza - Ospedale San Gerardo
state: Lombardia
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
state: Piemonte
city: Bari
country: Italy
facility: Policlinico di Bari
state: Puglia
city: ?ód?
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego
city: ?ód?
country: Poland
facility: Uniwersytecki Szpital Kliniczny im WAM CSW
city: Bia?ystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki im.dr.A.Jurasza w Bydgoszczy
city: Wroc?aw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University n.a. I.M. Sechenov
state: Moskovskaja Oblast
city: Rostov-na-donu
country: Russian Federation
facility: Rostov State Medical Uni
state: Rostov
city: Sankt-peterburg
country: Russian Federation
facility: German clinic
state: Sankt Petersburg
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Ankara
country: Turkey
facility: Hacettepe Uni School of Medicine
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty
city: Izmir
country: Turkey
facility: Ege Uni School of Medicine
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.