NCT05786768

Brief Summary

B-cell depletion with rituximab induces sustained remission in children with Steroid-Dependent or Frequent Relapsing Nephrotic Syndrome (SD/FRNS). However, most patients relapse after B-cell recovery and some do not achieve B-cell depletion. Obinutuzumab is a 2nd generation humanized monoclonal antiCD20 antibody, with enhanced B cell-depleting potential. It has been reported safe and efficient in different renal autoimmune diseases including childhood nephrotic syndrome. This double-blind, randomized multicenter study is designed to assess the efficacy and safety of a single infusion of low-dose obinutuzumab compared to a single infusion of rituximab in children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
88

participants targeted

Target at P50-P75 for phase_2

Timeline
20mo left

Started Oct 2023

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress61%
Oct 2023Dec 2027

First Submitted

Initial submission to the registry

February 10, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

March 28, 2023

Completed
7 months until next milestone

Study Start

First participant enrolled

October 18, 2023

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 18, 2027

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2027

Last Updated

November 9, 2023

Status Verified

January 1, 2023

Enrollment Period

4 years

First QC Date

February 10, 2023

Last Update Submit

November 8, 2023

Conditions

Steroid-Dependent Nephrotic SyndromeSteroid-Sensitive Nephrotic Syndrome

Keywords

RituximabObinutuzumabAnti-Drug Antibodies

Outcome Measures

Primary Outcomes (1)

  • Occurrence of a relapse within 12 months following the initiation of treatment

    Relapse is defined as a protein to creatinine ratio of 2 g/g of creatinine (0.20 g/mmol) or higher

    12 months

Secondary Outcomes (8)

  • Occurrence of a relapse within 24 months

    24 months

  • Time to B-cell depletion

    24 months

  • Duration of relapse-free survival after B-cell reconstitution

    24 months

  • Cumulative steroid courses and second line immunosuppressive treatments in patients with relape

    24 months

  • Safety associated with drug infusion

    24 months

  • +3 more secondary outcomes

Study Arms (2)

Rituximab 375 mg/m2

ACTIVE COMPARATOR

single infusion of Rituximab (375 mg/m2)

Drug: single infusion of Rituximab

Obinutuzumab 300 mg/1.73 m2

EXPERIMENTAL

single infusion of Obinutuzumab 300 mg/1.73 m2

Drug: single infusion of Obinutuzumab

Interventions

single infusion of RituximabDRUG

single infusion of Rituximab 375 mg/m2

Also known as: single infusion of Rituximab 375 mg/m2
Rituximab 375 mg/m2
single infusion of ObinutuzumabDRUG

single infusion of Obinutuzumab 300mg/1.73 m2

Also known as: single infusion of Obinutuzumab 300mg/1.73 m2
Obinutuzumab 300 mg/1.73 m2

Eligibility Criteria

Age3 Years - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Age between 3 and 18 years
  • Steroid dependant Nephrotic Syndrome defined as:
  • or more relapses during steroids or within 2 weeks following discontinuation.
  • or more relapses including one under steroid-sparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, levamisole) or within 6 months following treatment withdrawal
  • OR Frequent Relapsing Nephrotic Syndrome defined as:
  • or more relapses within 6 months following first remission
  • or more relapses within any 12-month period
  • In remission, defined as 3 consecutive urinary dipsticks without proteinuria, at the time of randomization
  • Vaccination schedule in accordance with the current recommendations in France
  • Informed consent from parents

You may not qualify if:

  • Secondary cause of nephrotic syndrome (such as membranous nephropathy, IgA nephropathy, lupus nephritis)
  • Primary or secondary steroid resistance nephrotic syndrome
  • Prior treatment with Rituximab within 6 months
  • Prior treatment with obinutuzumab at any time
  • CD20+ B-cell count \< 2.5%
  • Patient with neutrophils \< 1.5 G/L and/or platelets \< 75 G/L
  • GFR \< 80 ml/min/1.73m2
  • Weight \<16kg
  • History of severe infection such as tuberculosis, hepatitis B, hepatitis C or HIV infection or LEMP
  • History of malignancy- Uncontrolled infection (viral, bacterial and fungal)
  • Vaccination with a live vaccine within 4 weeks prior to assignment/randomization
  • Known hyperprolinemia
  • Hypersensitivity to the active substance (OBI or RTX) or to proteins of murine origin, or to any of the other excipients
  • Pregnancy or breastfeeding or ability to become pregnant and refusal to use effective contraception during the 18 months following the study treatment (only 1 infusion of obinutuzumab/Rituximab at the beginning of the study)
  • Patient without medical insurance coverage (beneficiary or legal)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Robert Debre Hospital

Paris, 75019, France

RECRUITING

Related Publications (3)

  • Dossier C, Sellier-Leclerc AL, Simon T, Parmentier C, Boyer O, Samaille C, Fila M, Roussey-Kesler G, Magnavacca M, Chartier Y, Louillet F, Zaloszyc A, Vrillon I, Elaribi D, Bouatia S, Kaguelidou F, Guilmin-Crepon S, Hogan J. Obinutuzumab versus Rituximab to maintain remission in children with steroid-dependent and frequently relapsing nephrotic syndrome: the OBIRINS study protocol, a double-blind randomised controlled trial. BMJ Open. 2025 Dec 24;15(12):e111980. doi: 10.1136/bmjopen-2025-111980.

    PMID: 41448676DERIVED

  • Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.

    PMID: 39513526DERIVED

  • Dossier C, Bonneric S, Baudouin V, Kwon T, Prim B, Cambier A, Couderc A, Moreau C, Deschenes G, Hogan J. Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children. Clin J Am Soc Nephrol. 2023 Dec 1;18(12):1555-1562. doi: 10.2215/CJN.0000000000000288. Epub 2023 Sep 6.

    PMID: 37678236DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Condition Hierarchy (Ancestors)

NephrosisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Study Officials

  • Claire DOSSIER, MD

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Claire DOSSIER, MD

CONTACT

+33140032467claire.dossier@aphp.fr

Julien HOGAN, MD PhD

CONTACT

+33140032142julien.hogan2@aphp.fr

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 10, 2023

First Posted

March 28, 2023

Study Start

October 18, 2023

Primary Completion (Estimated)

October 18, 2027

Study Completion (Estimated)

December 31, 2027

Last Updated

November 9, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will share
Shared Documents
STUDY PROTOCOL, ICF
Time Frame
48 months

Locations

FR(1)