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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04629248
Collaborator
(none)
140
69
2
83.2
2
0

Study Details

Study Description

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
140 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 25, 2021
Anticipated Primary Completion Date :
Jan 9, 2025
Anticipated Study Completion Date :
Jun 1, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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).

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

    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.

    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.

    Active Comparator: 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).

    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.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants who Achieve a Complete Remission (CR) at Week 104 [Week 104]

    Secondary Outcome Measures

    1. Percentage of Participants who Achieve an Overall Remission at Week 104 [Week 104]

    2. Percentage of Participants who Achieve CR at Week 76 [Week 76]

    3. Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission [Up to 8 years]

    4. Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline [Up to 8 years]

    5. 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.

    6. Duration of CR [Up to 8 years]

    7. Change in anti-PLA2R Autoantibody Titer [Baseline to Week 52]

    8. 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

    9. 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

    10. 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

    11. 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]

    12. 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]

    13. Prevalence of Anti-drug Antibodies (ADAs) to Obinutuzumab at Baseline [Open Label: Baseline; Escape Treatment: Week 0]

    14. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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/1.73m2 or qualified endogenous creatinine clearance >= 40 mL/min/1.73m2 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aventiv Research Inc Mesa Arizona United States 85201
    2 Keck School of Medicine - University of Southern California Los Angeles California United States 90033
    3 Kaiser Permanente - San Francisco Medical Center San Francisco California United States 94118
    4 Accel Research Sites; Mid-Florida Kidney and Hypertension Care Altamonte Springs Florida United States 32701
    5 University of Iowa Iowa City Iowa United States 52242
    6 Henry Ford Hospital; Div of Nephrology & Hypertension Detroit Michigan United States 48202
    7 Mayo Clinic; Nephrology and Hypertension Rochester Minnesota United States 55902
    8 North Shore University Hospital Manhasset New York United States 11030
    9 Columbia University Medical Center New York New York United States 10032
    10 Penn State Univ. Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033
    11 Prolato Clinical Research Center Houston Texas United States 77054
    12 Organizacion Medica de Investigacion Buenos Aires Argentina C1015ABO
    13 CINME Buenos Aires Argentina C1056ABJ
    14 Hospital Britanico Buenos Aires; Rheumatology Service Buenos Aires Argentina C1280AEB
    15 Hospital Italiano de Buenos Aires; Rheumatology department Ciudad Autónoma de Buenos Aires Argentina C1199ABD
    16 Ser Servicos Especializados Em Reumatologia Salvador BA Brazil 40150-150
    17 Hospital de Base de Sao Jose do Rio Preto Sao Jose do Rio Preto SP Brazil 15090-000
    18 Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos Sao Paulo SP Brazil 04038-002
    19 Hospital das Clinicas - FMUSP; Nefrologia Sao Paulo SP Brazil 05403-000
    20 Peking Union Medical College Hospital Beijing City China 100032
    21 Peking University First Hospital Beijing City China 100034
    22 West China Hospital - Sichuan University Chengdu City China 610047
    23 Sichuan Provincial People's Hospital Chengdu China 610072
    24 The 1st Affiliated hospital of Fujian Medical University Fuzhou City China 350005
    25 Nanfang Hospital, Southern Medical University Guangzhou China 510515
    26 Zhejiang Provincial People's Hospital Hangzhou China 310014
    27 Chinese People's Liberation Army Eastern Theater General Hospital Nanjing China
    28 Ruijin Hospital, Shanghai Jiaotong University School of Medicine Shanghai City China 200025
    29 Huashan Hospital, Fudan University Shanghai City China 200040
    30 Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan City China 430030
    31 The First Affiliated Hospital of Xian Jiao Tong University Xi'an City China 710061
    32 General Hospital of Ningxia Medical University Yinchuan China 750004
    33 Hopital La Cavale Blanche; Nephrologie Brest France 29609
    34 HOPITAL HENRI MONDOR; SERVICE DE Nephrologie Creteil France 94010
    35 Hopital Tenon; Service de Nephrologie et Dialyses Paris France 75020
    36 Hopital Bichat Claude Bernard; Nephrologie Paris France 75877
    37 Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique Toulouse France 31059
    38 Rambam Medical Center; Department of Nephrology and Hypertension Haifa Israel 3109601
    39 Hadassah Medical Orgainastion; Nephrology Jerusalem Israel 9112000
    40 Sheba MC; Nephrology Ramat-Gan Israel 5262000
    41 A.O. U. Federico II; U.O. di Nefrologia - Dipartimento di Sanità Pubblica Napoli Campania Italy 80131
    42 A.O. Spedali Civili Di Brescia-P.O. Spedali Civili; Nefrologia Brescia Lombardia Italy 25123
    43 ASST Monza - Ospedale San Gerardo; Clinica Nefrologica Monza Lombardia Italy 20900
    44 Ospedale San Giovanni Bosco; Unita Operativa Nefrologia Dialisi Torino Piemonte Italy 10154
    45 Policlinico di Bari; Divisione di Nefrologia, Dialisi e Trapianto Bari Puglia Italy 70124
    46 Uniwersytecki Szpital Kliniczny w Bialymstoku; II Klinika Nefrologii Białystok Poland 15-276
    47 Szpital Uniwersytecki im.dr.A.Jurasza w Bydgoszczy; Klinika Nefrologii, Nadcisnienia Tetniczego Bydgoszcz Poland 85-094
    48 Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu; Klinika Nefrologii Wrocław Poland 50-556
    49 Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego; Oddzial Nefrologii Łódź Poland 90-153
    50 Uniwersytecki Szpital Kliniczny im WAM CSW; Klinika Nefrologii i Transplantologii Nerek Łódź Poland 92-213
    51 Autonomous non-commercial organization "Medical Research Center of Drug Therapy "Yuninova" Sankt-peterburg Sankt Petersburg Russian Federation 194156
    52 German clinic Sankt-peterburg Sankt Petersburg Russian Federation 196128
    53 First Moscow State Medical University n.a. I.M. Sechenov Moscow Russian Federation 119991
    54 Rostov State Medical Uni ; Hematology Rostov-na-donu Russian Federation 344022
    55 Hospital Universitari de Bellvitge; Servicio de Nefrologia Hospitalet de Llobregat Barcelona Spain 08907
    56 Hospital Universitari Vall d'Hebron; Servicio de Nefrologia Barcelona Spain 08035
    57 Hospital Clinic i Provincial; Servicio de Nefrologia Barcelona Spain 08036
    58 Hospital General Universitaro Gregorio Marañon ;Servicio de Nefrologia Madrid Spain 28007
    59 Hospital Universitario 12 de Octubre; Servicio de Nefrologia Madrid Spain 28041
    60 Hospital Universitario Dr. Peset; Servicio de Nefrologia Valencia Spain 46017
    61 Hacettepe Uni School of Medicine; Nephrology Ankara Turkey 06100
    62 Akdeniz University Medical Faculty; Internal Medicine, Nephrology Antalya Turkey 07059
    63 Istanbul University Istanbul Medical Faculty; Department of Internal Medicine Istanbul Turkey 34390
    64 Ege Uni School of Medicine; Nephrology Izmir Turkey 35100
    65 Istanbul Florence Nightingale Hospital; Nephrology Şi̇şli̇ Turkey 34381
    66 Ternopil University Hospital Ternopil Kherson Governorate Ukraine 46002
    67 Oleksandrivska Clinical Hospital Kyiv KIEV Governorate Ukraine 01023
    68 Regional Clinical Hospital n.a I.I. Mechnicov Dnipropetrovsk Ukraine 49005
    69 Institute of Nephrology NAMS of Ukraine; Department of Nephrology, Dialysis and IT Support Kiev Ukraine 04050

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04629248
    Other Study ID Numbers:
    • WA41937
    • 2020-003233-38
    First Posted:
    Nov 16, 2020
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 18, 2022