OBINUTUZUMAB for Lupus nephritis (Class III or IV)

Inclusion criteria

• {"criterion_text":"- Adolescents ages 12 to <18 at the time of randomisation; younger cohort age 5 to < 12 at time of randomisation\n- International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV active LN demonstrated on renal biopsy performed in the 12 months prior to or during screening\n- Positive current or historical test for antinuclear antibody (ANA) and/or antibodies to double-stranded DNA (dsDNA)\n- Class V disease may be present in addition to Class III or IV LN, but participants with isolated Class V disease are not eligible\n- Significant proteinuria defined by a urine protein-to-creatinine ratio (UPCR) above >0.5 g/g based on a first-morning void (FMV) collection at screening\n- During the 12 months prior to or during screening, all participants must have received at least one dose of pulse-range IV methylprednisolone (typically 30 mg/kg, maximum of 1000 mg per dose) or equivalent for the treatment of the current episode of active LN"}

Exclusion criteria

• {"criterion_text":"- Severe, active central nervous system (CNS) SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia\n- Severe renal impairment, as indicated by glomerular filtration rate (GFR) within the past 6 months <30 mL/min/1.73m^2 estimated using the modified Bedside Schwartz equation or as indicated by the need for renal transplant, plasmapheresis or dialysis at screening\n- Sclerosis in >50% of glomeruli on renal biopsy and purely chronic Class III(c) or Class IV(c) disease on renal biopsy\n- Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV anti-infective medications within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization\n- History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ within the past 5 years\n- Significant or uncontrolled concomitant medical disease which, in the investigator’s opinion, would preclude participant participation"}

Primary endpoints

• {"endpoint_text":"- 1. Proportion of participants who achieve a complete renal response (CRR) at Week 76 (AP)","definition_or_measurement_approach":"Proportion of adolescent participants (AP) achieving CRR measured at Week 76."}
• {"endpoint_text":"- 2. Incidence, nature, and severity of AEs, Incidence of laboratory or vital sign abnormalities from baseline to Week 76 analysis and serum concentrations of obinutuzumab at specified timepoints (PP)","definition_or_measurement_approach":"Safety and PK endpoints in pediatric patients (PP): incidence/nature/severity of adverse events and laboratory/vital sign abnormalities from baseline to Week 76; serum obinutuzumab concentrations measured at specified timepoints."}

Secondary endpoints

• {"endpoint_text":"- 1. Proportion of adolescent participants achieving a CRR at Weeks 24 and 52 (AP)\n- 2. Proportion of participants who achieve CRR with successful prednisone taper at Week 76, defined as achievement of CRR (as above) at Week 76 with the following: – No receipt of prednisone > 7.5 mg/day (or equivalent) from Week 64 through Week 76\n- 3. Proportion of participants who achieve a partial renal response (PRR) at Week 76. PRR is defined as achievement of all of the following: – ≥ 50% reduction in UPCR from baseline – UPCR < 1 g/g (or < 3 g/g if the baseline UPCR was ≥ 3 g/g) – eGFR ≥ 85% of baseline – No occurrence of intercurrent events\n- 4. Proportion of adolescent participants achieving an overall response (CRR or PRR) at Weeks 24, 52, and 76 (AP)\n- 5. Change in urinary protein-to-creatinine ratio (UPCR) from baseline to Week 76 (AP)\n- 6. Change in estimated glomerular filtration rate (eGFR) from baseline to Week 76 (AP)\n- 7. Time to onset of CRR over the course of 76 weeks (AP)\n- 8. Proportion of participants who experience treatment failure from Week 12 to Week 76 (AP)\n- 9. Change in anti dsDNA titers from baseline to Week 76\n- 10. Change in C3 complement levels from baseline to Week 76 (AP)\n- 11. Change in C4 complement levels from baseline to Week 76 (AP)\n- 12. Incidence, nature, and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) from baseline to Week 76 (AP)\n- 13. Incidence of laboratory or vital sign abnormalities from baseline to Week 76 (AP)\n- 14. Serum concentrations of obinutuzumab at specified timepoints (AP)\n- 15. Proportion of participants achieving B-cell depletion, at specified timepoints\n- 16. Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue scale (PedsQL)-Fatigue total score from baseline to Week 76 (AP)\n- 17. Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) from baseline to Week 76 (AP)\n- 18. Change from baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) domain scores from baseline to Week 76 (AP)\n- 19. Proportion of participants with anti-drug antibodies (ADA) at weeks 0, 24, 52 and 76\n- 20. Relationship between ADA status and efficacy, safety, pharmacodynamic, or PK endpoints\n- 21. Proportion of patients achieving a complete renal response (CRR) at Week 76 (PP)\n- 22. Proportion of patients achieving an overall response, defined as achieving a complete or partial renal response (PRR) at Week 76 (PP)\n- 23. Proportion of participants who achieve CRR with successful prednisone taper at Week 76 ... (PP) – No receipt of prednisone > 7.5 mg/day (or equivalent) from Week 64 through Week 76\n- 24. Change in eGFR from baseline to Week 76 (PP)\n- 25. Change in anti-dsDNA titers from baseline to Week 76","definition_or_measurement_approach":"Secondary endpoints include proportions achieving CRR/PRR at specified weeks, changes from baseline in UPCR, eGFR, complement levels and dsDNA titers, time-to-event measures (time to CRR), safety measures (AE incidence and severity per NCI CTCAE), PK (serum obinutuzumab levels at specified timepoints), pharmacodynamic measures (B-cell depletion), immunogenicity (ADA at weeks 0,24,52,76), and patient-reported outcomes (PedsQL-Fatigue, CHQ-PF28, SLEDAI-2K). PRR is explicitly defined in the protocol as listed above."}

Methods

• Use of standard site-based recruitment materials: flyers, posters and patient brochures (documented recruitment materials include flyers, patient brochures, caregiver brochures, posters). Target audience: potential adolescent and pediatric patients and their caregivers.
• Use of referral letters and advocacy letters to support site recruitment (documents titled 'Referral Letter' and 'Advocacy letter').
• Site-based outreach at participating hospitals/clinics (nephrology/pediatric nephrology departments listed across member states).
• Recruitment facilitation tools for site staff such as flipcharts and visit guides (documents titled 'flipchart', 'visit guide').

Spain

Earliest CTIS Part Ii Submission Date

15-05-2023

Latest Decision Or Authorization Date

11-04-2025

Processing Time Days

697

Number Of Sites

4

Number Of Participants

5

France

Earliest CTIS Part Ii Submission Date

26-08-2024

Latest Decision Or Authorization Date

02-04-2025

Processing Time Days

219

Number Of Sites

4

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

15-05-2023

Latest Decision Or Authorization Date

23-04-2025

Processing Time Days

709

Number Of Sites

3

Number Of Participants

1

Poland

Earliest CTIS Part Ii Submission Date

15-05-2023

Latest Decision Or Authorization Date

03-05-2025

Processing Time Days

719

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

F. Hoffmann-La Roche AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA Limited

Responsibilities

sponsorDuties code: 1

Name

PPD Development LP

Responsibilities

sponsorDuties code: 4

Name

Endpoint Clinical Inc.

Responsibilities

sponsorDuties code: 3

Third parties

• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Pharmaceutical company"}