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Obinutuzumab for primary membranous nephropathy: a pilot study in patients with rituximab-resistant or rituximab-dependent nephrotic syndrome and in patients intolerant to rituximab (the ORION study)
EU CTIS ID: 2024-515857-93-00
What this study is testing
To evaluate whether rescue therapy with Obinutuzumab may induce remission of MN-related nephrotic syndrome in (1) Rituximab-Intolerant patients and in (2) Rituximab-Resistant or Rituximab-Dependent patients, and whether this drug is safe and well tolerated in these cohorts.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Adults (≥18 years old) on the day of signing informed consent.
- Compliance with an effective contraception without interruption, from 28 days before treatment start up to 18 months after treatment discontinuation, agreeing not to donate semen during treatment and for 18 months after discontinuation (if the patient is male), or to undergo pregnancy test during the course of the study (if the patient is female). (According to 2014 CTFG “Recommendations related to contraception and pregnancy testing in clinical trials”).
- 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 RASinhibitors (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 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
You likely can't join if
- Secondary forms of membranous nephropathy (associated with systemic lupus erythematosus, active hepatitis B, malignancy, drugs such as gold salts and penicillamine, and others).
- Known history of drug induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension.
- Pregnancy or breast-feeding.
- Childbearing potential and unwillingness or impossibility to comply with a scientifically acceptable birth-control method (According to 2014 CTFG “Recommendations related to contraception and pregnancy testing in clinical trials”).
- Legal incapacity, limited legal capacity, intellectual disability, uncooperative attitude or any other evidence that the patient will not be able to understand the study aims and procedures.
- Rituximab treatment or any other prolonged (i.e. for more than two weeks) immunosuppressive treatment in the 6 months preceding anti-CD20 infusion.
See the full eligibility criteria
Who can join
- Adults (≥18 years old) on the day of signing informed consent.
- Compliance with an effective contraception without interruption, from 28 days before treatment start up to 18 months after treatment discontinuation, agreeing not to donate semen during treatment and for 18 months after discontinuation (if the patient is male), or to undergo pregnancy test during the course of the study (if the patient is female). (According to 2014 CTFG “Recommendations related to contraception and pregnancy testing in clinical trials”).
- 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 RASinhibitors (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 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
- Failure to definitively and effectively respond to rituximab therapy because of 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
- Failure to definitively and effectively respond to rituximab therapy because of RITUXIMAB-DEPENDENCE: frequently-relapsing nephrotic syndrome (≥ 2 relapses) with nephrotic-range proteinuria for ≥ 50% of time in the 24 months preceding enrolment in patients who achieved initial remission after rituximab administration
- Estimated GFR/eGFR) ≥30 mL/min/1.73 m2 (calculated using the CKD-EPI equation) or qualified endogenous creatinine clearance ≥30 mL/min/1.73 m2 based on 24-hour urine collection during screening.
- Ability to understand and provide a valid written consent to the study according to the guidelines of the Declaration of Helsinki.
What rules you out
- Secondary forms of membranous nephropathy (associated with systemic lupus erythematosus, active hepatitis B, malignancy, drugs such as gold salts and penicillamine, and others).
- Known history of drug induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension.
- Pregnancy or breast-feeding.
- Childbearing potential and unwillingness or impossibility to comply with a scientifically acceptable birth-control method (According to 2014 CTFG “Recommendations related to contraception and pregnancy testing in clinical trials”).
- Legal incapacity, limited legal capacity, intellectual disability, uncooperative attitude or any other evidence that the patient will not be able to understand the study aims and procedures.
- 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.
- Patients with previous hepatitis B virus infection (seropositive for anti-HBcAb), planning a vaccination with live virus vaccines.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.