Obinutuzumab Treatment in Frequently Relapsing and Rituximab-Dependent Idiopathic Nephrotic Syndrome in Adults: a fully academic, single-arm, open, prospective, intervention trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Di Ricerche Farmacologiche Mario Negri

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

12 Mar 2026 → ongoing

Decision date (initial)

2026-02-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Roche's involvement is limited to providing the investigational drug

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the proportion of participants who are relapse-free for at least 12 months after obinutuzumab treatment*, administered as soon as remission is achieved by steroid treatment according to center practice. *in participant who relapsed within 12 month after rituximab prophylactic treatment withdrawal

Secondary objectives 6

1. To evaluate the effects of obinutuzumab treatment over a 12-month follow-up period, compared to baseline, on the following outcomes: Disease Relapse
2. To evaluate the effects of obinutuzumab treatment over a 12-month follow-up period, compared to baseline, on the following outcomes: B-cell replation
3. To evaluate the effects of obinutuzumab treatment over a 12-month follow-up period, compared to baseline, on the following outcomes: Kidney function
4. To evaluate the effects of obinutuzumab treatment over a 12-month follow-up period, compared to baseline, on the following outcomes: Component of the NS
5. To evaluate the effects of obinutuzumab treatment over a 12-month follow-up period, compared to baseline, on the following outcomes: Glomerular sieving function
6. To evaluate the effects of obinutuzumab treatment over a 12-month follow-up period, compared to baseline, on the following outcomes: Participant reported health-related quality of Life (hrQoL)

Conditions and MedDRA coding

Idiopathic Nephrotic Syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Adult age (≥18 years old)
2. 2. Rituximab-dependent idiopathic nephrotic syndrome is defined and confirmed as: a. Availability of a previous diagnostic kidney biopsy to confirm the diagnosis of MCD, FSGS or IgM glomerulonephritis and quantify the severity of chronic changes; b. Previous history of multi-relapsing, steroid-dependent nephrotic syndrome; c. Previous history (previous to start of the prophylactic protocol) of at least one relapse of the nephrotic syndrome after initial complete or partial remission and further remission∆ achieved by steroid; d. Relapse of the nephrotic syndrome within 12 months after withdrawal of rituximab prophylactic treatment defined as protein increase to >3.5g/24H or P/C>3500 mg/g along with serum albumin <3.5 g/dl.
3. Estimated GFR by the CKD-Epi creatinine equation (2021) ≥30 ml/min/1.73 m2
4. Ability to understand and provide a valid written consent to the study according to the guidelines of the Declaration of Helsinki and Good Clinical Practice
5. 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 participant is male). Furthermore, women should be advised to discontinue nursing during obinutuzumab therapy and for 18 months after the last dose of Obinutuzumab. (Please see the attached 2020 CTFG “Recommendations related to contraception and pregnancy testing in clinical trials”). Each female participant will undergo pregnancy test during the course of the study at fixed timepoints

Exclusion criteria 8

1. Concomitance of clinical conditions that could jeopardize completion of the treatment/observation period and/or confound data interpretation including: a) Active or recent (< 5 years before enrolment) history of malignancy; b) Other active systemic immune diseases requiring concomitant treatment with steroids or any other immunosuppressive agent; c) Severe/unstable heart failure requiring hospitalization or changes in pharmacological therapy; d) Refractory severe hypertension (BP >180/100 mmHg despite optimized pharmacological treatment with at least three blood pressure-lowering medications); e) Recent (within the last 4 weeks) severe infections requiring hospitalization or intravenous antibiotics; f) Known human immunodeficiency virus infection; g) Participants with previous hepatitis B virus infection who are seropositive for anti-HBcAb or subjects who are not immunized against HBV and subjects who are HBsAg-positive or anti-HBcAb positive alone. Subjects with both anti-HBsAb and anti-HBcAb (a condition that may reflect naturally cured infection) are eligible; h) Patients with untreated or not fully cured HCV infection; i) Planning a vaccination with live virus vaccines; j) Active bacterial, viral and/or fungal infections; k) Drug or alcohol abuse
2. Pregnancy, lactation, or intention to become pregnant before or during the study period, or up to 18 months of the last dose of study treatment
3. Intention to donate ova or sperm over the same time period
4. Childbearing potential without highly effective contraception methods according to the 2020 CTFG Recommendations related to contraception and pregnancy testing in clinical trials (https://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/CTFG/2020_09_HMA_CTFG_Contraception_guidance_Version_1.1_updated.pdf)
5. Known hypersensitivity to the active ingredient or any of the excipients of the study drug
6. Inability to fully understand the potential risks and benefits related to study participation
7. Participation in another interventional clinical study with an investigational product since the last month before enrolment
8. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of participants who are relapse-free for 12 months after Obinutuzumab treatment

Secondary endpoints 6

1. Time to protein increase to >3.5g/24H or P/C>3500 mg/g along with serum albumin <3.5 g/dl
2. Time to B-cell increase to > 5cells/mm3
3. Changes in Serum creatinine level, urea, eGFR (by CKD-Epi equation) and mGFR (measured at 6, 12, 18 and 24 months by the iohexol plasma clearance techniques).
4. Changes in hematologic parameters (serum total protein, albumin, total, LDL and HDl cholesterol, triglycerides) and in urine parameters (24-hour proteinuria and albuminuria) along with edema and body weight
5. Changes in total protein, albumin and IgG fractional clearances
6. Changes in participant health-related quality of life as measured by means of the SF-12 questionnaire

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Di Ricerche Farmacologiche Mario Negri

Sponsor organisation

Istituto Di Ricerche Farmacologiche Mario Negri

Address

Via Gian Battista Camozzi 3

City

Ranica

Postcode

24020

Country

Italy

Scientific contact point

Organisation

Istituto Di Ricerche Farmacologiche Mario Negri

Contact name

Dr Matias Trillini

Public contact point

Organisation

Istituto Di Ricerche Farmacologiche Mario Negri

Contact name

Dr Matias Trillini

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 13 files

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

Application history

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