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 range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Adults (≥18 years old) on the day of signing informed consent.
. Biopsy-proven primary membranous nephropathy.
. 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
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
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-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
. 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.