The MEMORINEPH study: Memory B cell level-based tailored treatment with Rixathon in children with complicated forms of steroid-sensitive Nephrotic syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale Pediatrico Bambino Gesu'

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Male Urogenital Diseases [C12]

Decision date (initial)

2024-10-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To define the optimal number of RTX re-infusions in children with complicated forms of FRNS/SDNS through an open-label randomized controlled trial comparing two different regimens for repeated RTX treatment based on the reconstitution of total B cells (Arm A) or memory B cells (Arm B).

Secondary objectives 2

1. In parallel we will evaluate the impact of the two different retreatment regimes with RTX on the number of relapses, days of hospitalization required and severe infections.
2. Exploratory aims: evaluate the effects on humoral immunity and the possible onset of anti-RTX antibodies by comparing the two different repeated RTX treatment regimens (A vs B).

Conditions and MedDRA coding

Complicated forms of idiopathic steroid-sensitive nephrotic syndrome (SSNS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1.Prior to any study procedure, informed consent must be obtained in written form from the adult patient or from both parents/legal guardians of the pediatric patient. For adolescent and school-aged patients, assent will be obtained with age-appropriate information. 2.Children and young adults (aged 3 to 24 years) with complicated forms of FRNS/SDNS (see "Definitions") who have at least 2 relapses per year while on mycophenolate mofetil (MMF) and/or a calcineurin inhibitor at appropriate doses (3-5 mg/kg in 2 daily doses). 3.Previous infusions of RTX will be allowed. 4.Patients, if of legal age, and parents or legal guardians if minors, must be able to communicate adequately with the medical team and understand and carry out the necessary procedures for completing the study. 5.For patients with reproductive potential (females), the use of a reliable contraceptive method (e.g., abstinence, barrier contraception, hormonal contraception) for the entire duration of study participation is required.

Exclusion criteria 1

1. At screening, patients with any of the following characteristics will not be considered eligible for enrollment: 1. Corticosteroid resistance, defined as lack of response to 4 weeks of oral prednisone at standard dosage. 2. Onset of nephrotic syndrome after the age of 18. 3. Secondary nephrotic syndrome. 4. Past or present malignant tumors of any organ or system, even in the absence of active or previous metastatic signs or symptoms. 5. Pregnancy (defined as the condition of a female individual from conception until the end of gestation, confirmed by a positive laboratory test for beta human chorionic gonadotropin (hCG)) or breastfeeding. Women of childbearing age (from menarche onward) must use an effective contraceptive method (complete abstinence, barrier contraception, or hormonal contraception) throughout the duration of the study and for 12 months following the last study RTX infusion. 6. Lack of response to rituximab or mycophenolate mofetil, defined as persistence of nephrotic proteinuria >4 weeks despite such therapy. 7. Active severe infection, for example, hepatitis B (positive HBsAg, HBcAb), sepsis, or active tuberculosis (positive Quantiferon). 8. Severe immunosuppression, defined as congenital immunodeficiency and/or as circulating immunoglobulin levels 2x lower than the minimum normal range for age and/or as circulating neutrophil granulocytes <1.5x10^3/μl. 9. Renal insufficiency with eGFR < 15 ml/min/1.73 m² calculated using the modified Schwartz formula (for children) or the Cockcroft-Gault formula (for adults). 10. Severe heart failure (New York Heart Association class IV) or severe uncontrolled heart disease. 11. Known hypersensitivity to RTX treatment. 12. Known hypersensitivity to concomitant medications (prednisone, mycophenolate mofetil/mycophenolic acid, calcineurin inhibitors). 13. Use of live attenuated vaccines within 28 days prior to enrollment and throughout the duration of the study. 14. Weight < 10 kg. 15. Thrombocytopenia, defined as platelet level <100,000/mm². 16. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels >2.5x the upper limit of the normal range for age and sex.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluation of the number of RTX re-infusions comparing the two therapeutic regimens based on flow cytometry assessment of total B cell reconstitution (Arm A) or memory (Arm B) during a 24-month follow-up

Secondary endpoints 2

1. Assessment during a 24-month follow-up of: • The number of relapses (defined as the reappearance of massive proteinuria (>40 mg/m²/h in children or urine protein/creatinine ratio > 2 g/g) or a positive urine dipstick (≥3+ for 3 days or positive for 7 days), with or without edema); • The number of hospitalization days; • The number of severe infections (defined as infections requiring hospitalization); • The time to the first relapse or a positive urine dipstick
2. Exploratory endpoints: Evaluation using immunoturbidimetry and ELISA tests of serum levels of total immunoglobulins IgG, IgM, and IgA, as well as antibody titers specific to tetanus and HBV induced by vaccination. • Assessment of the incidence of prolonged hypogammaglobulinemia (defined as IgG levels < age-specific normal range) and/or severe hypogammaglobulinemia (IgG < 250 mg/dl), with potential need for the introduction of replacement therapy with IgG.

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale Pediatrico Bambino Gesu'

Sponsor organisation

Ospedale Pediatrico Bambino Gesu'

Address

Piazza Sant'onofrio 4

City

Rome

Postcode

00165

Country

Italy

Scientific contact point

Organisation

Ospedale Pediatrico Bambino Gesu'

Contact name

Marina Vivarelli

Public contact point

Organisation

Ospedale Pediatrico Bambino Gesu'

Contact name

Marina Vivarelli

Locations

1 EU/EEA country · 2 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 36 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