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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

29 Oct 2021 → ongoing

Decision date (initial)

2024-09-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann La Roche

External identifiers

EU CT number

2023-505825-15-00

EudraCT number

2021-000097-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Others, Safety, Pharmacokinetic, Efficacy

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

Secondary objectives 10

1. To evaluate the efficacy of obinutuzumab compared with placebo (AP)
2. To evaluate the safety of obinutuzumab compared with placebo (AP)
3. To characterize obinutuzumab pharmacokinetic (PK) profile (AP)
4. To characterize obinutuzumab pharmacodynamic (PD) profile
5. To evaluate changes in fatigue of participants treated with obinutuzumab compared with placebo (AP)
6. To evaluate change in SLE disease activity of participants treated with obinutuzumab compared with placebo (AP)
7. To evaluate changes in the quality of life of participants treated with obinutuzumab compared with placebo (AP)
8. To evaluate the efficacy of obinutuzumab (PP)
9. To evaluate the immune response to obinutuzumab
10. To evaluate autoantibodies over time (PP)

Conditions and MedDRA coding

Lupus Nephritis (LN)

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adolescents ages 12 to <18 at the time of randomisation; younger cohort age 5 to < 12 at time of randomisation
2. 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
3. Positive current or historical test for antinuclear antibody (ANA) and/or antibodies to double-stranded DNA (dsDNA)
4. Class V disease may be present in addition to Class III or IV LN, but participants with isolated Class V disease are not eligible
5. 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
6. 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 6

1. Severe, active central nervous system (CNS) SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia
2. 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
3. Sclerosis in >50% of glomeruli on renal biopsy and purely chronic Class III(c) or Class IV(c) disease on renal biopsy
4. 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
5. History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ within the past 5 years
6. Significant or uncontrolled concomitant medical disease which, in the investigator’s opinion, would preclude participant participation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Proportion of participants who achieve a complete renal response (CRR) at Week 76 (AP)
2. 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 endpoints 25

1. 1. Proportion of adolescent participants achieving a CRR at Weeks 24 and 52 (AP)
2. 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. 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. 4. Proportion of adolescent participants achieving an overall response (CRR or PRR) at Weeks 24, 52, and 76 (AP)
5. 5. Change in urinary protein-to-creatinine ratio (UPCR) from baseline to Week 76 (AP)
6. 6. Change in estimated glomerular filtration rate (eGFR) from baseline to Week 76 (AP)
7. 7. Time to onset of CRR over the course of 76 weeks (AP)
8. 8. Proportion of participants who experience treatment failure from Week 12 to Week 76 (AP)
9. 9. Change in anti dsDNA titers from baseline to Week 76
10. 10. Change in C3 complement levels from baseline to Week 76 (AP)
11. 11. Change in C4 complement levels from baseline to Week 76 (AP)
12. 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. 13. Incidence of laboratory or vital sign abnormalities from baseline to Week 76 (AP)
14. 14. Serum concentrations of obinutuzumab at specified timepoints (AP)
15. 15. Proportion of participants achieving B-cell depletion, at specified timepoints
16. 16. Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue scale (PedsQL)-Fatigue total score from baseline to Week 76 (AP)
17. 17. Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) from baseline to Week 76 (AP)
18. 18. Change from baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) domain scores from baseline to Week 76 (AP)
19. 19. Proportion of participants with anti-drug antibodies (ADA) at weeks 0, 24, 52 and 76
20. 20.Relationship between ADA status and efficacy, safety, pharmacodynamic, or PK endpoints
21. 21. Proportion of patients achieving a complete renal response (CRR) at Week 76 (PP)
22. 22. Proportion of patients achieving an overall response, defined as achieving a complete or partial renal response (PRR) at Week 76 (PP)
23. 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. 24. Change in eGFR from baseline to Week 76 (PP)
25. 25. Change in anti-dsDNA titers from baseline to Week 76

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 4

Locations

4 EU/EEA countries · 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 72 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications