A Study to Evaluate Efficacy and Safety of Obinutuzumab in Patients with Primary Membranous Nephropathy
- Conditions
- Primary Membranous Nephropathy (pMN)MedDRA version: 21.1Level: LLTClassification code 10027170Term: Membranous nephropathySystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2020-003233-38-IT
- Lead Sponsor
- F. HOFFMANN - LA ROCHE LTD.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 140
•Age 18-75 years
•Diagnosis of pMN according to renal biopsy prior to or during screening
•Urinary protein-to-creatinine ratio (UPCR) >= 5 g from 24-hour urine collection despite best supportive care for >= 3 months prior to screening or UPCR >= 4 g despite best supportive care >= 6 months prior to screening
•Systolic blood pressure <= 140 mmHg and diastolic blood pressure <= 90 mmHg at screening
•eGFR >= 40 mL/min/1.73m2 or qualified endogenous creatinine clearance >= 40 mL/min based on 24-hour urine collection during screening
•Patients who previously responded to calcineurin inhibitor (CNIs), rituximab, or alkylating agents with either a CR or partial remission and subsequently relapsed are eligible but require discontinuation of CNIs or alkylating agents for >= 6 months and rituximab for >= 9 months prior to screening
•For women of childbearing potential: agreement to remain abstinent or use adequate contraception during the treatment period and for 18 months after the final dose of obinutuzumab and for 28 days after the final dose of tacrolimus
•For men receiving tacrolimus: agreement to remain abstinent or use a condom, as defined below: With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 28 days after the final dose of tacrolimus to avoid exposing the embryo
•For patients enrolled in the extended China enrollment phase at National Medical Products Administration-recognized sites: current resident of mainland China and of Chinese ancestry
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 119
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 21
•Patients with a secondary cause of MN
•Uncontrolled blood pressure, in the opinion of the investigator, during 3 months prior to screening
•Evidence of >= 50% reduction in proteinuria during the previous 6 months prior to screening
•Receipt of renal replacement therapy
•Type 1 or 2 diabetes mellitus
•Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or 28 days after the final dose of tacrolimus
•History of resistance (no response) to CNIs or B-cell depleting antibodies
•Receipt of previous therapies as follows:
oTreatment with MMF or oral, intramuscular, or intravenous corticosteroids within 1 month prior to screening
oAny B-cell depleting therapy such as rituximab, ocrelizumab, or ofatumumab within 9 months prior to screening
oTreatment with cyclophosphamide or CNI within 6 months prior to screening
oTreatment with any biologic therapy such as belimumab, ustekinumab, or anifrolumab within 6 months prior to screening
oTreatment with an inhibitor of Janus-associated kinase, Bruton’s tyrosine kinase, or tyrosine kinase 2, including but not limited to tofacitinib, baricitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib within 3 months prior to screening
oTreatment with any investigational agent within 28 days of screening or 5 drug-elimination half-lives of the investigational drug, whichever is longer
oReceipt of a live vaccine within 28 days prior to screening or during screening
•Thrombocytopenia, anemia, and/or coagulopathy with high risk for clinically significant bleeding or organ dysfunction or requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions
•Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation
•Known HIV infection
•Tuberculosis infection
•Known active infection of any kind, excluding fungal infection of the nail beds
•Any major episode of infection requiring hospitalization or treatment either with IV anti-infective treatments during the 2 months prior to or during screening or with oral anti-infective treatments during the 2 weeks prior to or during screening
•History of serious recurrent or chronic infection, progressive multifocal leukoencephalopathy, cancer, carcinoma in situ, except non-melanomatous carcinomas of the skin that have been treated or excised and have resolved
•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, including:
oEvidence of intolerance or toxicity associated with tacrolimus prior to screening
oHistory of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion
oIntolerance or contraindication to oral or IV corticosteroids and premedications
oIntolerance or hypersensitivity to tacrolimus and its excipients
oLack of peripheral venous access
•Laboratory parameters
oaspartate aminotransferase or alanine transaminase > 2.5 ×the upper limit of normal (ULN)
oAmylase or lipase > 2 × ULN
oNeutrophils < 1.5 × 103/micro L
oCD19+ B cells < 5/micro L
oPositive for hepatitis B surface antigen (HBsAg) at screening
oPositive hepatitis C virus antibody at screening
oHemoglobin < 9 g/dL
oPlatelet count < 75,000/micro L
oPositive serum human chorionic gon
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method