Early rituximab treatment in children with idiopathic nephrotic syndrome Eng. ERICONS - Early RITUXIMAB in Childhood Onset Nephrotic Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Gdansk

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

17 Dec 2021 → ongoing

Decision date (initial)

2024-11-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency (Agencja Badań Medycznych)

External identifiers

EU CT number

2024-515058-26-00

EudraCT number

2020-004982-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy

Assessment of the duration of disease remission in the study group compared to placebo

Secondary objectives 1

1. 1. Assessment of treatment failure in the study group compared to placebo 2. Assessment of the total dose of steroids administered in the test group compared to placebo 3. Assessment of B-cell depletion as an indicator of the risk of recurrence in the study group compared to placebo 4. Assessment of the duration of remission in the unblinded phase of the study 5. Optimizing RTX dosing 6. Assessment of the impact of the presence of anti-RTX antibodies on the effectiveness and presence of allergic reactions 7. Assessment of the effect of hypogammaglobulinemia on the duration of remission in the study group compared to placebo 8. Understanding the risk factors for the disease and how to respond to treatment with steroid-dependent NS

Conditions and MedDRA coding

NEPHROTIC SYNDROME

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Expresses the willingness to participate in the study and after obtaining information about the study, the patient / legal guardians will sign an informed consent form for participation in the study 2. Age at study entry> 2 years (> 24 months of age) and under 16 years of age 3. Meet the criteria for diagnosis of idiopathic steroid-dependent nephrotic syndrome (two relapses during steroid dose reduction or within two weeks of stopping steroid therapy) or nephrotic syndrome with frequent relapses (two or more relapses in 6 months on steroid therapy or four or more relapses in a period of 12 months) 4. Remission of NS immediately prior to study entry, defined as the absence or trace of protein in the urinalysis [uPCR <0.2 mg protein / mg creatinine (<20 mg protein / mmol creatinine) or <1+ in the test strip] for 3 consecutive days 5. Patients of childbearing age (conception) will commit to abstinence or to use effective contraception during the study period and up to 12 months after stopping RTX treatment; girls of childbearing potential will have a negative pregnancy test on qualifying for treatment initiation

Exclusion criteria 1

1. 1. Previous use of immunosuppressants such as cyclophosphamide, cyclosporin A, tacrolimus, mycophenolate mofetil, levamisole 2. Diagnosis of steroid-resistant NS, nephritic syndrome or secondary NS 3. Previous severe infection (tuberculosis, systemic mycosis), HIV, HCV, HBV infection 4. Active infection 5. Severe heart diseases (heart failure, myocardial infarction, severe heart rhythm disturbances) 6. Vaccinations with live vaccines within 4 weeks prior to study inclusion 7. Poorly controlled hypertension 8. Abnormal kidney function (eGFR <90 ml / min) 9. Autoimmune disease (IgA vasculitis, systemic lupus) 10. Current or history of cancer 11. Status after organ transplantation 12. Allergy to methylprednisolone, paracetamol, cetirizine, co-trimoxazole 13. Laboratory abnormalities: leukocyte count <3000 / µl, neutrocyte count <1500 / µl, platelet count <75,000 / µl, severe liver dysfunction: ALT or AST 2.5 times upper limit of normal 14. Prior treatment with monoclonal antibodies 15. Use of another study drug within the 6 months prior to study entry, or participation in other studies at screening 16. Severe immunodeficiency 17. Pregnancy, breastfeeding or refusal to use methods of contraception in case of the ability to become pregnant (pregnancy test required - beta hCG in the blood serum at enrollment in the study) 18. Hypersensitivity to the active substance, mouse proteins, or any of the excipients of the study drug (i.e. sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water for injections)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Relapse-free survival (defined as the occurrence of proteinuria persisting for ≥ 3 days during the blinded phase (from day 1 to day 365)).

Secondary endpoints 4

1. Time to treatment failure 1a. Percentage of failures in the experimental and placebo groups.
2. Total dose of administered steroids.
3. Time from depletion resolution to relapse.
4. Relapse-free survival during the open-label phase (from the day of investigational drug administration to day 365 of observation).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Gdansk

Sponsor organisation

Medical University Of Gdansk

Address

Ul. Marii Sklodowskiej-Curie 3a

City

Gdansk

Postcode

80-210

Country

Poland

Scientific contact point

Organisation

Medical University Of Gdansk

Contact name

Chief Medical Officer; Principal Investigator

Public contact point

Organisation

Medical University Of Gdansk

Contact name

Director of Clinical Research Support Centre

Locations

1 EU/EEA country · 9 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 8 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