Efficacy and Safety of Obinutuzumab versus Rituximab in childhood Steroid Dependant and Frequent Relapsing Nephrotic Syndrome : à double-blind multicenter randomized controlled study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

31 Oct 2024 → ongoing

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministray of Health (PHRC-20)

External identifiers

EU CT number

2024-514240-93-00

EudraCT number

2022-003336-59

ClinicalTrials.gov

NCT05786768

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the superiority of one infusion of obinutuzumab compared to one infusion of rituximab on the relapse-free survival at 12-months.

Secondary objectives 10

1. To assess the superiority of obinutuzumab compared to rituximab on the relapse-free survival at 24-months
2. To compare the duration of B-cell depletion after OBI and RTX
3. To compare the relapse-free survival after B-cell recovery after OBI and RTX
4. To compare the number of relapses, steroid courses and second line treatment strategies required within 24 months in both arms
5. To compare the safety of the two treatments including infusion-related reactions, infections, levels of immunoglobulins, neutropenia
6. To assess the factors associated with sustained remission
7. To assess the cost-effectiveness of the OBI strategy
8. To assess the budgetary impact of the generalization of the OBI strategy
9. To assess pharmacokinetics of Obinutuzumab and Rituximab
10. To assess the development of antidrug antibodies

Conditions and MedDRA coding

Idiopathic nephrotic syndrome (INS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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

Exclusion criteria 15

1. Secondary cause of nephrotic syndrome (such as membranous nephropathy, IgA nephropathy, lupus nephritis)
2. Primary or secondary steroid resistance nephrotic syndrome
3. Prior treatment with Rituximab within 6 months
4. Prior treatment with obinutuzumab at any time
5. CD20+ B-cell count < 2.5%
6. Patient with neutrophils < 1.5 G/L and/or platelets < 75 G/L
7. GFR < 80 ml/min/1.73m2
8. - Weight <16kg
9. History of severe infection such as tuberculosis, hepatitis B, hepatitis C or HIV infection or LEMP
10. History of malignancy- Uncontrolled infection (viral, bacterial and fungal)
11. Vaccination with a live vaccine within 4 weeks prior to assignment/randomization
12. Known hyperprolinemia
13. Hypersensitivity to the active substance (OBI or RTX) or to proteins of murine origin, or to any of the other excipients
14. 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)
15. Patient without medical insurance coverage (beneficiary or legal)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome is the occurrence of a relapse defined as a 3+ proteinuria on dipstick on 3 consecutive days, with 1 laboratory urine dosage of Protein-over-creatinine ratio > 0.20g/mmol (> 0.2g/g), within 12 months following the initiation of Treatment.

Secondary endpoints 10

1. To assess the superiority of obinutuzumab compared to rituximab on the relapse-free survival at 24-months
2. To compare the duration of B-cell depletion after OBI and RTX
3. To compare the relapse-free survival after B-cell recovery after OBI and RTX
4. To compare the number of relapses, steroid courses and second line treatment strategies required within 24 months in both arms
5. To compare the safety of the two treatments including infusion-related reactions, infections, levels of immunoglobulins, neutropenia
6. To assess the factors associated with sustained remission
7. To assess the cost-effectiveness of the OBI strategy
8. To assess the budgetary impact of the generalization of the OBI strategy
9. To assess pharmacokinetics of Obinutuzumab and Rituximab
10. To assess the development of antidrug antibodies

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 13 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 10 files

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

Application history

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