A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis and the Safety and PK of Obinutuzumab in Pediatric Patients (Aged 5 To < 12) (POSTERITY)
- Conditions
- Lupus Nephritis (LN)
- Registration Number
- 2023-505825-15-00
- Lead Sponsor
- F. Hoffmann-La Roche AG
- Brief Summary
To evaluate the efficacy of obinutuzumab compared with placebo in adolescent participants (AP) with Class III/IV LN To evaluate the safety of obinutuzumab and characterize the obinutuzumab PK profile in pediatric patients (PP) aged 5 to <12 with LN
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 10
Adolescents ages 12 to <18 at the time of randomisation; younger cohort age 5 to < 12 at time of randomisation
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
Positive current or historical test for antinuclear antibody (ANA) and/or antibodies to double-stranded DNA (dsDNA)
Class V disease may be present in addition to Class III or IV LN, but participants with isolated Class V disease are not eligible
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
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
Severe, active central nervous system (CNS) SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia
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
Sclerosis in >50% of glomeruli on renal biopsy and purely chronic Class III(c) or Class IV(c) disease on renal biopsy
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
History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ within the past 5 years
Significant or uncontrolled concomitant medical disease which, in the investigator’s opinion, would preclude participant participation
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Proportion of participants who achieve a complete renal response (CRR) at Week 76 (AP) 1. Proportion of participants who achieve a complete renal response (CRR) at Week 76 (AP)
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) 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)
- Secondary Outcome Measures
Name Time Method 1. Proportion of adolescent participants achieving a CRR at Weeks 24 and 52 (AP) 1. Proportion of adolescent participants achieving a CRR at Weeks 24 and 52 (AP)
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 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
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 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
4. Proportion of adolescent participants achieving an overall response (CRR or PRR) at Weeks 24, 52, and 76 (AP) 4. Proportion of adolescent participants achieving an overall response (CRR or PRR) at Weeks 24, 52, and 76 (AP)
5. Change in urinary protein-to-creatinine ratio (UPCR) from baseline to Week 76 (AP) 5. Change in urinary protein-to-creatinine ratio (UPCR) from baseline to Week 76 (AP)
6. Change in estimated glomerular filtration rate (eGFR) from baseline to Week 76 (AP) 6. Change in estimated glomerular filtration rate (eGFR) from baseline to Week 76 (AP)
7. Time to onset of CRR over the course of 76 weeks (AP) 7. Time to onset of CRR over the course of 76 weeks (AP)
8. Proportion of participants who experience treatment failure from Week 12 to Week 76 (AP) 8. Proportion of participants who experience treatment failure from Week 12 to Week 76 (AP)
9. Change in anti dsDNA titers from baseline to Week 76 9. Change in anti dsDNA titers from baseline to Week 76
10. Change in C3 complement levels from baseline to Week 76 (AP) 10. Change in C3 complement levels from baseline to Week 76 (AP)
11. Change in C4 complement levels from baseline to Week 76 (AP) 11. Change in C4 complement levels from baseline to Week 76 (AP)
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) 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)
13. Incidence of laboratory or vital sign abnormalities from baseline to Week 76 (AP) 13. Incidence of laboratory or vital sign abnormalities from baseline to Week 76 (AP)
14. Serum concentrations of obinutuzumab at specified timepoints (AP) 14. Serum concentrations of obinutuzumab at specified timepoints (AP)
15. Proportion of participants achieving B-cell depletion, at specified timepoints 15. Proportion of participants achieving B-cell depletion, at specified timepoints
17. Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) from baseline to Week 76 (AP) 17. Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) from baseline to Week 76 (AP)
18. Change from baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) domain scores from baseline to Week 76 (AP) 18. Change from baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) domain scores from baseline to Week 76 (AP)
19. Proportion of participants with anti-drug antibodies (ADA) at weeks 0, 24, 52 and 76 19. Proportion of participants with anti-drug antibodies (ADA) at weeks 0, 24, 52 and 76
20.Relationship between ADA status and efficacy, safety, pharmacodynamic, or PK endpoints 20.Relationship between ADA status and efficacy, safety, pharmacodynamic, or PK endpoints
21. Proportion of patients achieving a complete renal response (CRR) at Week 76 (PP) 21. Proportion of patients achieving a complete renal response (CRR) at Week 76 (PP)
22. Proportion of patients achieving an overall response, defined as achieving a complete or partial renal response (PRR) at Week 76 (PP) 22. Proportion of patients achieving an overall response, defined as achieving a complete or partial renal response (PRR) at Week 76 (PP)
23. 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 (PP) – No receipt of prednisone > 7.5 mg/day (or equivalent) from Week 64 through Week 76 23. 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 (PP) – No receipt of prednisone > 7.5 mg/day (or equivalent) from Week 64 through Week 76
24. Change in eGFR from baseline to Week 76 (PP) 24. Change in eGFR from baseline to Week 76 (PP)
25. Change in anti-dsDNA titers from baseline to Week 76 25. Change in anti-dsDNA titers from baseline to Week 76
16. Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue scale (PedsQL)-Fatigue total score from baseline to Week 76 (AP) 16. Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue scale (PedsQL)-Fatigue total score from baseline to Week 76 (AP)
Trial Locations
- Locations (10)
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Hospital Universitario Y Politecnico La Fe
🇪🇸Valencia, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Sant Joan De Deu Barcelona
🇪🇸Esplugues De Llobregat, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
IRCCS Istituto Giannina Gaslini
🇮🇹Genoa, Italy
Ospedale Pediatrico Bambino Gesu
🇮🇹Rome, Italy
Assistance Publique Hopitaux De Paris
🇫🇷Le Kremlin-Bicetre, France
Centre Hospitalier Universitaire De Toulouse
🇫🇷Toulouse Cedex 9, France
Uniwersyteckie Centrum Kliniczne🇵🇱Gdansk, PolandAleksandra ŻurowskaSite contact+583492850nefrologiadziecieca@uck.gda.pl