BOOSTER – Multicenter, Open Label, Randomized Control Phase III Trial Comparing the Efficacy and Safety of Two Rituximab Regimens in Maintenance Therapy for Relapsing Nephrotic Syndrome Due to Podocytopathies in Adults. (B cell Depletion Therapy to Improve Outcomes of Relapsing STERoid-sensitive Podocytopathies in Adults – BOOSTER trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Lodz

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

28 Apr 2025 → ongoing

Decision date (initial)

2025-02-10

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Polish Medical Research Agency

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To compare the efficacy of two Rituximab treatment regimens in terms of time to nephrotic syndrome recurrence (non-inferiority hypothesis).

Secondary objectives 6

1. Comparison of the efficacy of two rituximab treatment regimens in terms of time to nephrotic syndrome relapse (superiority hypothesis).
2. Comparison of the effectiveness of two rituximab treatment regimens in maintaining remission for 24 months after randomization.
3. Comparison of rituximab treatment regimens in terms of glucocorticoids use in 24 months after randomization.
4. Evaluation of the impact of rituximab treatment on health-related quality of life.
5. Evaluation of the prevalence of serious adverse events.
6. Evaluation of the prevalence of adverse events of special interest.

Conditions and MedDRA coding

Idiopathic steroid-sensitive nephrotic syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Informed consent to participate in the study.
2. Age of at least 18 years.
3. Diagnosis of podocytopathy of the most likely primary (immune-mediated) nature, meeting all of the following criteria: a. Histopathological diagnosis of MCD (Minimal Change Disease) or FSGS (Focal Segmental Glomerulosclerosis)*; AND b. A history of good response to standard-dose glucocorticoids treatment - defined as complete remission of nephrotic syndrome within 16 weeks of treatment with prednisone at a dose of up to 1 mg/kg/day, max. 80 mg/day (or equivalent dose of another glucocorticoid) or up to 2mg/kg/48h, max. 120 mg (or equivalent dose of another glucocorticoid) preceded or not preceded by the administration of intravenous glucocorticoids; c. Excluded secondary causes of nephrotic syndrome. *It is acceptable to include a patient without or with a non-diagnostic biopsy result as long as criteria 3b and 3c are met and the disease course is typical of podocytopathy and the differential diagnosis does not support another diagnosis. Each case should be considered individually, in consultation with the Coordinating Investigator.
4. A relapsing course of disease that meets all of the following criteria: a. At least 1 relapse of nephrotic syndrome in the history; b. Last relapse of nephrotic syndrome within 2 years prior to study inclusion that occurred during immunosuppressive therapy or within 6 months of its withdrawal.
5. Ongoing immunosuppressive treatment to maintain remission after the last relapse lasting min. 2 weeks and max. 100 weeks (patients with SD (steroid-dependence)/FR (frequent relapses)) from achieving partial or complete remission.
6. At the time of inclusion in the study, at least partial remission of disease with proteinuria < 1.0 g/day (or uPCR <1000 mg/g) achieved with treatment with glucocorticoids and/or glucocorticoids-sparing immunosuppressant.

Exclusion criteria 9

1. Probable or certain secondary cause of podocytopathy, including, but not limited to, chronic use of medications with a confirmed association with MCD (Minimal Change Disease) (e.g., lithium salts, interferon, non-steroidal anti-inflammatory drugs), paraneoplastic syndrome, podocyte protein mutations.
2. Treatment with cyclophosphamide within 6 months prior to study inclusion.
3. Treatment with rituximab within 18 months prior to study inclusion.
4. Presence of any of the contraindications to the administration of rituximab (according to the SmPC): a. Hypersensitivity to the active substance or excipients; b. Hypersensitivity to mouse proteins; c. Active infection with a severe course; d. Severe immunodeficiency*; e. Pregnancy, breastfeeding, or refusal to use effective pregnancy prevention methods during the study (applies to women); f. Severe heart failure (NYHA class IV) or severe uncontrolled heart disease. g. Post-vaccination status with a live vaccine within 4 weeks prior to study inclusion. * Immunoglobulin G deficiency secondary to nephrotic syndrome, as well as immunoglobulin G deficiency with serum IgG levels >250 g/L without a history of severe infectious complications, should not be considered as an absolute exclusion criterion. Each case should be considered individually.
5. A positive result on any of the following virology tests: a. Presence of anti-HIV antibodies; b. Presence of anti-HCV antibodies** and HCV RNA viremia; c. Presence of HBs antigen. If anti-HCV antibodies are found, the patient may be eligible for the study provided that HCV RNA viremia is absent.
6. Glomerular filtration rate - eGFR less than 45 ml/min/1.73m2 according to the CKD-EPI 2021 formula.
7. Hypersensitivity to drugs used for premedication and prophylaxis of opportunistic infections, including corticosteroids, paracetamol, clemastine, cotrimoxazole (sulfamethoxazole+trimethoprim, SMX/TMP).
8. Active neoplastic disease or history of neoplastic disease in the last 5 years.
9. Any other abnormality or disease not described above that excludes the patient from the study based on the Investigator's assessment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time from randomization to first relapse of nephrotic syndrome (non-inferiority hypothesis).

Secondary endpoints 6

1. Time from randomization to first relapse of nephrotic syndrome (superiority hypothesis).
2. Percentage of nephrotic syndrome relapse within 24 months.
3. Cumulative dose of glucocorticoids administered within 24 months of randomization.
4. Absolute values and differences from the entry assessment in the number of points obtained in the EQ-index (EQ-index) and analog scale (EQ-VAS) according to the EQ-5D-5L questionnaire at 24 months after randomization.
5. Severe adverse event rate.
6. Rate of adverse events of special interest.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Lodz

Sponsor organisation

Medical University Of Lodz

Address

Al. Tadeusza Kosciuszki 4

City

Lodz

Postcode

90-419

Country

Poland

Scientific contact point

Organisation

Medical University Of Lodz

Contact name

Clinical Trial Support Unit

Public contact point

Organisation

Medical University Of Lodz

Contact name

Clinical Trial Support Unit

Locations

1 EU/EEA country · 12 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 11 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