Obinutuzumab in Primary MN (NCT05050214) | Clinical Trial Compass
Active — Not RecruitingPhase 2
Obinutuzumab in Primary MN
Italy20 participantsStarted 2022-02-18
Plain-language summary
Primary membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease, that represents one of the most frequent causes of nephrotic syndrome in adults. The first-generation chimeric anti-CD20 monoclonal antibody rituximab is effective in inducing MN remission in the majority of patients, but a significant fraction of them can experience disease relapses that require multiple re-treatments over time. Repeated infusions may result in hypersensitivity reactions, which contraindicate further treatment with rituximab. Independent of previous treatment response, Rituximab-Intolerant patients require a safe and effective therapeutic alternative that could reduce the risk of hypersensitivity reactions. On the other end a substantial proportion of patients do not benefit of rituximab therapy and might benefit of other anti CD20 monoclonal antibodies. A few patients transiently benefit of rituximab but their relapses after rituximab administration are so frequent that they spend most of their live with nephrotic range proteinuria (rituximab-dependent patients). Obinutuzumab is a humanized monoclonal antibody with enhanced B cell-depleting potential. Due to humanization and glycoengineering, this drug may be safe and effective in inducing disease remission even in patients with prior hypersensitivity reactions to rituximab. Moreover, it has been found to be effective in patients with membranous nephropathy who failed to respond to rituximab.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Adults (≥18 years old) on the day of signing informed consent.
✓. Availability of a recent (over the last six months) diagnostic kidney biopsy to confirm the diagnosis of membranous nephropathy and quantify the severity of chronic changes and the number of glomerular podocytes.
✓. High-risk of progression to end-stage kidney disease due to persistent nephrotic-range proteinuria (urinary protein excretion \> 3.5 g/24-hours as a median of three consecutive measurements) despite background treatment with RAS-inhibitors (ACEi and/or ARBs) at the maximum tolerated doses for at least six months before inclusion.
✓. Failure to definitively and effectively respond to rituximab therapy because of the following:
✓. RITUXIMAB-INTOLERANCE, i.e. any previous severe hypersensitivity reaction to rituximab (acute grade III or IV adverse reactions requiring advanced care, or late reactions including delayed serum sickness syndrome) that, independent of response to treatment, preclude further exposure to the drug; or
✓. RITUXIMAB-RESISTANCE: no evidence of nephrotic syndrome complete remission (24-hour proteinuria \< 0.3 g/day, normal serum albumin and stable renal function) or partial remission (24-hour proteinuria \< 3.5 g/day with \> 50% decrease from baseline, normal serum albumin and stable renal function) along with detectable circulating CD19+ lymphocytes for at least 6 months after rituximab administration or
What they're measuring
1
Complete remission or partial remission of nephrotic syndrome.
Timeframe: Changes from baseline and 12 months from Obinutuzumab treatment .
2
Serious and non-serious adverse events
Timeframe: Through study completion, an average of 24 months.
Trial details
NCT IDNCT05050214
SponsorMario Negri Institute for Pharmacological Research
✓. RITUXIMAB-DEPENDENCE: frequently-relapsing nephrotic syndrome (≥ 2 relapses) with nephrotic-range proteinuria for ≥ 50% of time in the 24 months preceding enrolment initial remission after rituximab administration
Exclusion criteria
✕. Secondary forms of membranous nephropathy (associated with systemic lupus erythematosus, active hepatitis B, malignancy, drugs such as gold salts and penicillamine, and others).
✕. Rituximab treatment or any other prolonged (i.e. for more than two weeks) immunosuppressive treatment in the 6 months preceding anti-CD20 infusion.
✕. Uncontrolled hypertension (systolic BP ≥160 and/or diastolic BP \>90 mmHg despite therapy).
✕. Active bacterial, viral and/or fungal infections.
✕. Seropositivity for HIV, regardless of viral load.
✕. Active or recent (\< 5 years before enrolment) history of malignancy.
✕. Known hypersensitivity or allergy to any of the medicaments under investigation.
✕. Any other serious medical condition, uncontrolled intercurrent illness or laboratory abnormality that, according to the investigator's judgement, would constitute an unacceptable risk of premature discontinuation from the study.