A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Patients with ISN/RPS 2003 Class III or IV Lupus Nephritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

16 Jul 2020 → ongoing

Decision date (initial)

2024-01-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2023-503628-22-00

EudraCT number

2019-004034-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Safety

1. To evaluate the efficacy of obinutuzumab (combined treatment groups) compared with placebo based on the proportion of patients who achieve a complete renal response (CRR) at Week 76

Secondary objectives 6

1. 1. To evaluate the efficacy of obinutuzumab compared with placebo based on the proportion of patients who achieve a proteinuric response at Week 76, proportion of patients who achieve CRR with successful prednisone taper at Week 76, overall renal response (ORR) at Week 50, proportion of patients who experience death or renal-related events and mean change in estimated glomerular filtration rate (eGFR) from baseline to Week 76, change in anti-double stranded deoxyribonucleic acid (anti-dsDNA) titer and C3 from baseline to Week 50, change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI2K) from baseline to Week 76, time to onset of CRR and change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale from baseline to Week 76, proportion of patients who achieve CRR with serum creatinine criteria at Week 76
2. 2. To evaluate safety of obinutuzumab compared with placebo
3. 3. To characterize obinutuzumabpharmacokinetic profile
4. 4. To evaluate immune response to obinutuzumab
5. 5. To characterize obinutuzumab-induced changes in circulating B cells
6. 6. To evaluate the efficacy of obinutuzumab on long-term kidney health after study unblinding during the Long-Term Extension Study Period

Conditions and MedDRA coding

Lupus Nephritis (LN)

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 1. Active or active/chronic International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV proliferative LN by renal biopsy performed in the 6 months prior to screening or during screening
2. 2. Systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria, which are met by the presence of Class III or IV LN (above) and current or past positive antinuclear antibody (ANA), as evidenced by ANA at a titer of >= 1:80 on hEp-2 cells or an equivalent positive ANA test at least once
3. 3. Urinary protein-to-creatinine ratio (UPCR) ≥ 1 g/g on a 24-hour collection at screening
4. 4. Receipt of at least one dose of pulse methylprednisolone IV (≥ 250 mg) or equivalent for treatment of the current episode of active LN during the 6 months prior to screening or during screening; or to be given on Day 1 prior to the first infusion. A maximum of 3 g methylprednisolone IV or equivalent during the 4 weeks prior to screening or during screening is allowed

Exclusion criteria 6

1. 1. Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or placebo or within 6 weeks after the final dose of MMF
2. 2. Severe renal impairment, as defined by eGFR < 30 mL/min/1.73 m2 or the need for dialysis or renal transplantation
3. 3. Sclerosis in > 50% of glomeruli on renal biopsy
4. 4. Presence of rapidly progressive glomerulonephritis
5. 5. Severe, active central nervous system SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia
6. 6. High risk for clinically-significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Proportion of patients who achieve a CRR at Week 76

Secondary endpoints 24

1. 1. Proportion of patients who achieve a proteinuric response at Week 76
2. 2. Proportion of patients who achieve CRR with successful prednisone taper at Week 76
3. 3. Proportion of patients who achieve an ORR evaluated at Week 50
4. 4. Proportion of patients who experience death or renal-related events through Week 76
5. 5. Mean change in eGFR from baseline to Week 76
6. 6. Change in anti-dsDNA titer from baseline to Week 50
7. 7. Change in C3 from baseline to Week 50
8. 8. Change in SLEDAI-2K from baseline to Week 76
9. 9. Time to onset of CRR over the course of 76 weeks
10. 10. Change in FACIT-F scale from baseline to Week 76
11. 11. Proportion of patients who achieve CRR with serum creatinine criteria at Week 76
12. 12. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)
13. 13. To characterize adverse events of special interest, including, among others, infusion-related reactions (IRRs), neutropenia, infections, and thrombocytopenia
14. 14. Change from baseline in targeted vital signs
15. 15. Change from baseline in targeted clinical laboratory test results
16. 16. Maximum observed concentration (Cmax) of obinutuzumab
17. 17. Minimum observed concentration (Cmin) of obinutuzumab
18. 18. Area under concentration-time curve (AUC) of obinutuzumab
19. 19. Clearance (CL) of obinutuzumab
20. 20. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs post-treatment during the study
21. 21. Total peripheral B-cell count at specified timepoints
22. 22. Time to lupus nephritis (LN) flare
23. 23. Time to unfavorable kidney outcome
24. 24. Mean change in eGFR from baseline, eGFR slope and proportion of participants achieving CRR over time

Investigational products

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

Test 2

Placebo 1

Auxiliary 4

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 Support Line - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line - TISL

Third parties 3

Locations

5 EU/EEA countries · 23 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 43 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