A Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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.
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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.
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Outcome Measures
Primary Outcome Measures
- Percentage of Participants who Achieve a Complete Remission (CR) at Week 104 [Week 104]
Secondary Outcome Measures
- 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]
Self-reported changes in fatigue will be measured using the PROMIS Fatigue Scale.
- Duration of CR [Up to 8 years]
- Change in anti-PLA2R Autoantibody Titer [Baseline to Week 52]
- 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
- 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
- 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]
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of primary membranous nephropathy (pMN) according to renal biopsy prior to or during screening
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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
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eGFR >= 40 mL/min/1.73m2 or qualified endogenous creatinine clearance >= 40 mL/min/1.73m2 based on 24-hour urine collection during screening
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Other inclusion criteria may apply
Exclusion Criteria:
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Participants with a secondary cause of MN
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Pregnancy or breastfeeding
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Evidence of >= 50% reduction in proteinuria during the previous 6 months prior to randomization
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Severe renal impairment, including the need for dialysis or renal replacement therapy
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Type 1 or 2 diabetes mellitus
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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
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Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude participant participation
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Known active infection of any kind or recent major episode of infection
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Major surgery requiring hospitalization within the 4 weeks prior to screening
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Current active alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening
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Intolerance or contraindication to study therapies
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Other exclusion criteria may apply
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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.- WA41937
- 2020-003233-38