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

Primary Membranous Nephropathy Clinical Trial

— MAJESTY  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04629248
• Other study ID #: WA41937
• Secondary ID: 2020-003233-3820
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 25, 2021
• Est. completion date: December 29, 2027

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 140
• Est. completion date: December 29, 2027
• Est. primary completion date: December 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Kidney Diseases
• Primary Membranous Nephropathy

Intervention

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

Locations

Country	Name	City	State
Argentina	CINME	Buenos Aires
Argentina	Hospital Britanico Buenos Aires; Rheumatology Service	Buenos Aires
Argentina	Organizacion Medica de Investigacion	San Nicolás
Brazil	Ser Servicos Especializados Em Reumatologia	Salvador	BA
Brazil	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP
Brazil	Hospital das Clinicas - FMUSP; Nefrologia	Sao Paulo	SP
Brazil	Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos	Sao Paulo	SP
China	Peking Union Medical College Hospital	Beijing City
China	Peking University First Hospital	Beijing City
China	Sichuan Provincial People's Hospital	Chengdu
China	West China Hospital - Sichuan University	Chengdu City
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	Huashan Hospital, Fudan University	Shanghai City
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai City
China	Tongji Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	The First Affiliated Hospital of Xian Jiao Tong University	Xi'an City
China	General Hospital of Ningxia Medical University	Yinchuan
France	HOPITAL HENRI MONDOR; SERVICE DE Nephrologie	Creteil
France	Hopital Tenon; Service de Nephrologie et Dialyses	Paris
France	Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique	Toulouse
Israel	Sheba MC; Nephrology	Ramat-Gan
Italy	Policlinico di Bari; Divisione di Nefrologia, Dialisi e Trapianto	Bari	Puglia
Italy	A.O. Spedali Civili Di Brescia-P.O. Spedali Civili; Nefrologia	Brescia	Lombardia
Italy	ASST Monza - Ospedale San Gerardo; Clinica Nefrologica	Monza	Lombardia
Italy	A.O. U. Federico II; U.O. di Nefrologia - Dipartimento di Sanità Pubblica	Napoli	Campania
Italy	Ospedale San Giovanni Bosco; Unita Operativa Nefrologia Dialisi	Torino	Piemonte
Poland	Uniwersytecki Szpital Kliniczny im WAM CSW; Klinika Nefrologii i Transplantologii Nerek	?ód?
Poland	Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego; Oddzial Nefrologii	?ód?
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku; II Klinika Nefrologii	Bia?ystok
Poland	Szpital Uniwersytecki im.dr.A.Jurasza w Bydgoszczy; Klinika Nefrologii, Nadcisnienia Tetniczego	Bydgoszcz
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu; Klinika Nefrologii	Wroc?aw
Russian Federation	First Moscow State Medical University n.a. I.M. Sechenov	Moscow	Moskovskaja Oblast
Russian Federation	Rostov State Medical Uni ; Hematology	Rostov-na-donu	Rostov
Russian Federation	German clinic	Sankt-peterburg	Sankt Petersburg
Spain	Hospital Clinic i Provincial; Servicio de Nefrologia	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Servicio de Nefrologia	Barcelona
Spain	Hospital Universitari de Bellvitge; Servicio de Nefrologia	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario 12 de Octubre; Servicio de Nefrologia	Madrid
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Turkey	Hacettepe Uni School of Medicine; Nephrology	Ankara
Turkey	Akdeniz University Medical Faculty; Internal Medicine, Nephrology	Antalya
Turkey	Ege Uni School of Medicine; Nephrology	Izmir
Ukraine	Regional Clinical Hospital n.a I.I. Mechnicov	Dnipropetrovsk
Ukraine	Ternopil University Hospital	Ternopil	Kherson Governorate
United States	Accel Research Sites; Mid-Florida Kidney and Hypertension Care	Altamonte Springs	Florida
United States	University of Colorado in Denver-Anschutz Medical Campus	Aurora	Colorado
United States	Nephrotex Research Group	Dallas	Texas
United States	Henry Ford Hospital; Div of Nephrology & Hypertension	Detroit	Michigan
United States	University of Iowa	Iowa City	Iowa
United States	Aventiv Research Inc	Mesa	Arizona
United States	Columbia University Medical Center	New York	New York
United States	Mayo Clinic; Nephrology and Hypertension	Rochester	Minnesota
United States	Kaiser Permanente - San Francisco Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  China,  France,  Israel,  Italy,  Poland,  Russian Federation,  Spain,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who Achieve a Complete Remission (CR) at Week 104		Week 104
Secondary	Percentage of Participants who Achieve an Overall Remission at Week 104		Week 104
Secondary	Percentage of Participants who Achieve CR at Week 76		Week 76
Secondary	Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission		Up to 8 years
Secondary	Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline		Up to 8 years
Secondary	Mean Change in T-score from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Week 104	Self-reported changes in fatigue will be measured using the PROMIS Fatigue Scale.	Baseline to Week 104
Secondary	Duration of CR		Up to 8 years
Secondary	Change in anti-PLA2R Autoantibody Titer		Baseline to Week 52
Secondary	Mean Change from Baseline in the PROMIS Global Assessment of Physical Health Scale at Week 104	Self-reported changes in physical health will be measured using the PROMIS Physical Health Scale	Baseline to Week 104
Secondary	Percentage of Participants with Adverse Events (AEs)	Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	Up to 8 years
Secondary	Percentage of Participants with AEs of Special Interest (AESIs)	AESIs are required to be reported by the investigator to the Sponsor immediately	Up to 8 years
Secondary	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
Secondary	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
Secondary	Prevalence of Anti-drug Antibodies (ADAs) to Obinutuzumab at Baseline		Open Label: Baseline; Escape Treatment: Week 0
Secondary	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