A randomized controlled, two-arm (1:1 ratio) Phase IIa trial to assess the efficacy and safety of obinutuzumab in treating adults with de novo minimal change disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medizinische Universitaet Innsbruck

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-04-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Monetary support from ANR (French National Research Agency) · Monetary support from FWF (Austrian Science Fund) · Material support (Obinutuzumab) from Roche

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare the efficacy of obinutuzumab versus standard of care (standard regimen of oral glucocorticoid therapy; progressively tapered over 24 weeks) in the management of newly onset biopsy-proven minimal change disease in its non-inferiority and further in its superiority.

Secondary objectives 4

1. To investigate the impact of obinutuzumab versus standard of care on time to remission, time to disease relapse, patient-reported health-related quality of life (QoL) and glucocorticoid toxicity
2. To compare the safety of obinutuzumab versus standard of care
3. To investigate potential predictors of disease relapse, independent of treatment assignment (“general risk factors")
4. Exploratory objective: To investigate the potential of experimental biomarkers to predict treatment response, sustained remission/relapse and specific side effects

Conditions and MedDRA coding

Kidney disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Understands and agrees to comply with the study procedures and provides informed consent as documented by signature
2. Male or female patients aged 18 years or older at the time of consent
3. 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
4. Histologically confirmed MCD (latest before randomization to Arm A or B)
5. 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)
6. Only applies to trial sites in France: Patients affiliated with the French health care system

Exclusion criteria 14

1. 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)
2. Pregnant or breast-feeding women
3. Live vaccine administration in the four weeks prior to screening and during the study duration of 52 weeks
4. Previous/known hypersensitivity to predniso(lo)ne or obinutuzumab or to any of the excipients to be in accordance with the SmPC of Gazyvaro
5. Co-enrolment in another clinical trial of an investigational medicinal product
6. Family history of MCD or in a first degree relative unless previously shown to be steroid-responsive
7. 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
8. Previous cyclophosphamide within 6 months preceding baseline of the trial
9. Treatment with predniso(lo)ne within screening phase (before randomization)
10. 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)
11. Evidence of active severe infection requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to first dose of study drug
12. Severe heart failure or severe, uncontrolled cardiac disease (NYHA class III or IV)
13. 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
14. Any other reason which, in the opinion of the Principal Investigator (PI), renders the patient unsuitable for the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Non-inferiority of obinutuzumab to SoC predniso(lo)ne taper: Proportions of patients achieving remission (complete or partial) of MCD at 8 weeks
2. 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

Secondary endpoints 17

1. Time to remission (either complete or partial)
2. Time to complete remission
3. Time to disease relapse
4. Change in Glucocorticoid Toxicity Index (GTI) from baseline to day 60, week 26 and 52
5. Change in urinary protein-to-creatinine ratio/albumin-to-creatinine ratio from baseline to week 26 and 52
6. Change in serum albumin from baseline to week 26 and 52
7. Kidney function as assessed by changes in 2021 race-free CKD-EPI estimated glomerular filtration rate (eGFR) from baseline to week 26 and 52
8. Patient-reported health–related QoL assessed by EuroQol 5-Dimensions 5-Levels Questionnaire (EQ-5D-5L)
9. Predictors of disease relapse (independent of treatment assignment): Demographics, clinical characteristics, biological variables and histopathological characteristics
10. Safety endpoint: Serious adverse events (assessed by CTCAE v5; defined as grade ≥3) during the study period of 52 weeks
11. Safety endpoint: Adverse events of special interest (AESI) and infection events during the study period of 52 weeks
12. 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
13. Exploratory endpoint: Sequential measurement of anti-nephrin antibodies, and value of anti-nephrin antibodies to predict treatment response and relapse
14. 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
15. Exploratory endpoint: The association between development of anti-obinutuzumab antibodies and quantitative levels of obinutuzumab and treatment response and sustained remission rates
16. 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
17. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medizinische Universitaet Innsbruck

Sponsor organisation

Medizinische Universitaet Innsbruck

Address

Innrain 52

City

Innsbruck

Postcode

6020

Country

Austria

Scientific contact point

Organisation

Medizinische Universitaet Innsbruck

Contact name

University Hospital for Internal Medicine IV (Nephrology and Hypertensiology)

Public contact point

Organisation

Medizinische Universitaet Innsbruck

Contact name

University Hospital for Internal Medicine IV (Nephrology and Hypertensiology)

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications