OBINUTUZUMAB for Minimal change disease | Nephrotic syndrome

Inclusion criteria

• {"criterion_text":"- Understands and agrees to comply with the study procedures and provides informed consent as documented by signature"}
• {"criterion_text":"- Male or female patients aged 18 years or older at the time of consent"}
• {"criterion_text":"- Confirmed first episode of nephrotic syndrome at trial enrolment (serum albumin <30g/l and UPCR >3g/g creatinine (>300mg/mmol) secondary to de novo MCD"}
• {"criterion_text":"- Histologically confirmed MCD (latest before randomization to Arm A or B)"}
• {"criterion_text":"- Only applies to women of childbearing potential (WOCBP): 5a) Has a high sensitivity negative urine/serum pregnancy test at screening 5b) Agrees to follow contraceptive guidance until 18 months after 2nd obinutuzumab treatment (if randomized to Arm B)"}
• {"criterion_text":"- Only applies to trial sites in France: Patients affiliated with the French health care system"}

Exclusion criteria

• {"criterion_text":"- MCD due to secondary causes, including malignancy of a type likely to be associated with MCD (i.e., lymphoproliferative disorders), or potentially related to treatment known to be associated with MCD occurrence (lithium, interferon, non-steroidal anti-inflammatory drugs)"}
• {"criterion_text":"- Pregnant or breast-feeding women"}
• {"criterion_text":"- Live vaccine administration in the four weeks prior to screening and during the study duration of 52 weeks"}
• {"criterion_text":"- Previous/known hypersensitivity to predniso(lo)ne or obinutuzumab or to any of the excipients to be in accordance with the SmPC of Gazyvaro"}
• {"criterion_text":"- Co-enrolment in another clinical trial of an investigational medicinal product"}
• {"criterion_text":"- Family history of MCD or in a first degree relative unless previously shown to be steroid-responsive"}
• {"criterion_text":"- Previous B cell depletion, independent of the agent and treatment target (i.e., CD20, CD38, etc.), within 18 months preceding baseline of the trial, or 12 months if there is evidence of B cell return in peripheral lymphocyte subsets"}
• {"criterion_text":"- Previous cyclophosphamide within 6 months preceding baseline of the trial"}
• {"criterion_text":"- Treatment with predniso(lo)ne within screening phase (before randomization)"}
• {"criterion_text":"- Evidence of current or past infection with Hepatitis B, C or Human Immunodeficiency Virus (HIV) (unless appropriate prophylaxis is given and no replicating virus is detected)"}
• {"criterion_text":"- Evidence of active severe infection requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to first dose of study drug"}
• {"criterion_text":"- Severe heart failure or severe, uncontrolled cardiac disease (NYHA class III or IV)"}
• {"criterion_text":"- Patient with a history of prior malignancy within 5 years before the first dose of study drug. Exceptions may apply for the following: malignancies with a negligible risk of metastasis or death such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer"}
• {"criterion_text":"- Any other reason which, in the opinion of the Principal Investigator (PI), renders the patient unsuitable for the trial."}

Primary endpoints

• {"endpoint_text":"- Non-inferiority of obinutuzumab to SoC predniso(lo)ne taper: Proportions of patients achieving remission (complete or partial) of MCD at 8 weeks","definition_or_measurement_approach":"Proportion of patients achieving complete or partial remission of MCD at 8 weeks (binary outcome measured as remission status at Week 8)"}
• {"endpoint_text":"- Superiority of obinutuzumab to SoC prednis(lo)ne taper: Proportions of patients sustaining remission (complete or partial)/prevent relapses of MCD during the study period of 52 weeks","definition_or_measurement_approach":"Proportion of patients sustaining complete or partial remission / not experiencing relapse during the 52-week study period (binary outcome over 52 weeks)"}

Secondary endpoints

• {"endpoint_text":"- Time to remission (either complete or partial)","definition_or_measurement_approach":"Time (days/weeks) from baseline to first documented remission (complete or partial)"}
• {"endpoint_text":"- Time to complete remission","definition_or_measurement_approach":"Time from baseline to first documented complete remission"}
• {"endpoint_text":"- Time to disease relapse","definition_or_measurement_approach":"Time from remission to documented disease relapse"}
• {"endpoint_text":"- Change in Glucocorticoid Toxicity Index (GTI) from baseline to day 60, week 26 and 52","definition_or_measurement_approach":"Change from baseline in GTI score measured at day 60, week 26 and week 52"}
• {"endpoint_text":"- Change in urinary protein-to-creatinine ratio/albumin-to-creatinine ratio from baseline to week 26 and 52","definition_or_measurement_approach":"Change from baseline in UPCR/ACR measured at week 26 and week 52"}
• {"endpoint_text":"- Change in serum albumin from baseline to week 26 and 52","definition_or_measurement_approach":"Change from baseline in serum albumin measured at week 26 and week 52"}
• {"endpoint_text":"- Kidney function as assessed by changes in 2021 race-free CKD-EPI estimated glomerular filtration rate (eGFR) from baseline to week 26 and 52","definition_or_measurement_approach":"Change from baseline in eGFR (2021 race-free CKD-EPI) measured at week 26 and week 52"}
• {"endpoint_text":"- Patient-reported health–related QoL assessed by EuroQol 5-Dimensions 5-Levels Questionnaire (EQ-5D-5L)","definition_or_measurement_approach":"EQ-5D-5L questionnaire scores collected at scheduled visits"}
• {"endpoint_text":"- Predictors of disease relapse (independent of treatment assignment): Demographics, clinical characteristics, biological variables and histopathological characteristics","definition_or_measurement_approach":"Exploratory/statistical analyses of baseline demographics, clinical, biological and histopathology variables as predictors of relapse"}
• {"endpoint_text":"- Safety endpoint: Serious adverse events (assessed by CTCAE v5; defined as grade ≥3) during the study period of 52 weeks","definition_or_measurement_approach":"Incidence of SAEs graded by CTCAE v5 (grade ≥3) over 52 weeks"}
• {"endpoint_text":"- Safety endpoint: Adverse events of special interest (AESI) and infection events during the study period of 52 weeks","definition_or_measurement_approach":"Incidence of predefined AESIs and infection events over 52 weeks"}
• {"endpoint_text":"- Safety endpoint: The proportion of patients with overall and mild hypogammaglobulinemia (<7g/L), moderate hypogammaglobulinemia (<5g/L) and severe hypogammaglobulinemia (<3g/L) at baseline, week 26 and week 52","definition_or_measurement_approach":"Proportion of patients meeting specified IgG thresholds (<7, <5, <3 g/L) at baseline, week 26 and week 52"}
• {"endpoint_text":"- Exploratory endpoint: Sequential measurement of anti-nephrin antibodies, and value of anti-nephrin antibodies to predict treatment response and relapse","definition_or_measurement_approach":"Serial measurement of anti-nephrin antibodies and association analyses with response and relapse"}
• {"endpoint_text":"- Exploratory endpoint: Identification of B and T cell subsets to predict treatment response, relapse and side effects in the obinutuzumab and the standard of care arm","definition_or_measurement_approach":"Immunophenotyping of B and T cell subsets and correlational analyses with outcomes"}
• {"endpoint_text":"- Exploratory endpoint: The association between development of anti-obinutuzumab antibodies and quantitative levels of obinutuzumab and treatment response and sustained remission rates","definition_or_measurement_approach":"Measurement of anti-drug antibodies and drug levels; association with response and remission"}
• {"endpoint_text":"- Exploratory endpoint: Single cell RNA sequencing signature predictive of response to treatment, time to remission, sustained remission and risk of side effects in the obinutuzumab and the standard of care arm","definition_or_measurement_approach":"Single cell RNA-seq signatures correlated with clinical outcomes"}
• {"endpoint_text":"- Exploratory endpoint: Differentially expressed proteins/lipids (assessed by plasma/PBMC proteomics and plasma lipidomics) distinguish patients who will achieve remission and will have a disease relapse","definition_or_measurement_approach":"Proteomics and lipidomics analyses of plasma/PBMC to identify differential markers associated with remission/relapse"}

Other endpoints

• {"endpoint_text":"- Exploratory endpoint: Sequential measurement of anti-nephrin antibodies, and value of anti-nephrin antibodies to predict treatment response and relapse","definition_or_measurement_approach":"Serial measurement of anti-nephrin antibodies and association analyses with response and relapse"}
• {"endpoint_text":"- Exploratory endpoint: Identification of B and T cell subsets to predict treatment response, relapse and side effects in the obinutuzumab and the standard of care arm","definition_or_measurement_approach":"Immunophenotyping of B and T cell subsets and correlational analyses with outcomes"}
• {"endpoint_text":"- Exploratory endpoint: The association between development of anti-obinutuzumab antibodies and quantitative levels of obinutuzumab and treatment response and sustained remission rates","definition_or_measurement_approach":"Measurement of anti-drug antibodies and drug levels; association with response and remission"}
• {"endpoint_text":"- Exploratory endpoint: Single cell RNA sequencing signature predictive of response to treatment, time to remission, sustained remission and risk of side effects in the obinutuzumab and the standard of care arm","definition_or_measurement_approach":"Single cell RNA-seq signatures correlated with clinical outcomes"}
• {"endpoint_text":"- Exploratory endpoint: Differentially expressed proteins/lipids (assessed by plasma/PBMC proteomics and plasma lipidomics) distinguish patients who will achieve remission and will have a disease relapse","definition_or_measurement_approach":"Proteomics and lipidomics analyses of plasma/PBMC to identify differential markers associated with remission/relapse"}

Austria

Earliest CTIS Part Ii Submission Date

26-03-2026

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

32

Number Of Sites

3

Number Of Participants

18

France

Earliest CTIS Part Ii Submission Date

07-04-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

16

Number Of Sites

2

Number Of Participants

24

Germany

Earliest CTIS Part Ii Submission Date

23-03-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

31

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Medizinische Universitaet Innsbruck

Organisation Type

Educational Institution

Country Of Registered Address

Austria

Third parties

• {"country":"","full_name":"Monetary support from ANR (French National Research Agency)","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Monetary support from FWF (Austrian Science Fund)","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Material support (Obinutuzumab) from Roche","duties_or_roles":"Material support (provision of obinutuzumab)","organisation_type":""}