A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Patients with Systemic Lupus Erythematosus (ALLEGORY)

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], Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

4 Nov 2021 → ongoing

Decision date (initial)

2024-03-22

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

2023-504774-38-00

EudraCT number

2020-005760-57

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Others

To evaluate the efficacy of obinutuzumab compared with placebo based on proportion of participants who achieve systemic lupus erythematosus responder index (SRI) (4)

Secondary objectives 4

1. 1. To evaluate the efficacy of obinutuzumab compared with placebo based on proportion of participants who achieve SRI (6), and SRI (4), proportion of participants entering the study on prednisone ≥ 10 mg/day (or equivalent) who achieve sustained corticosteroid control, proportion of participants who achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), proportion of participants who achieve Lupus Low Disease Activity State (LLDAS), DORIS, time to first British Isles Lupus Assessment Group (BILAG) flare, change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale from baseline, change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain domain scale from baseline and change in SF-36 v2 Physical Component Summary scale from baseline
2. 2. To evaluate the safety of obinutuzumab compared with placebo
3. 3. To characterize the obinutuzumab pharmacokinetic (PK) profile
4. 4. To evaluate the immune response to obinutuzumab

Conditions and MedDRA coding

Systemic Lupus Erythematosus (SLE)

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, 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 6

1. Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria ≥12 weeks prior to screening
2. Anti-nuclear antibody (ANA) ≥1:80, or anti-dsDNA and/or anti-Sm antibodies above the upper limit of normal (ULN), as determined by the central laboratory at screening
3. Low C3 or low C4 or low CH50 complement as determined by the central laboratory at screening Low C3 is required in the presence of known genetic deficiency of C4
4. High disease activity at screening, based on; British Isles Lupus Assessment Group (BILAG-2004) (Category A disease in ≥1 organ system and/or Category B disease in ≥2 organ systems), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (score ≥8) and Physician’s Global Assessment (PGA) (score ≥1.0 on a 0 to 3 visual analogue scale [VAS])
5. High disease activity on Day 1, based on; SLEDAI-2K (score ≥8) and PGA (score ≥1.0 on a 0 to 3 VAS)
6. Current receipt of ≥1 of the following classes of standard therapies for the treatment of SLE at stable doses: oral corticosteroid (OCS), antimalarials, conventional immunosuppressants

Exclusion criteria 6

1. Pregnancy or breastfeeding
2. Presence of significant lupus-associated renal disease and/or renal impairment
3. Receipt of an excluded therapy, including any anti-CD20, anti-CD19 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
4. Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation
5. Known active infection of any kind or recent major episode of infection
6. Intolerance or contraindication to study therapies

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Proportion of participants who achieve Systemic Lupus Erythematosus Responder Index (SRI)(4) at Week 52

Secondary endpoints 24

1. 1. Proportion of participants who achieve SRI(6) at Week 52
2. 2. Proportion of participants entering the study on prednisone ≥ 10 mg/day (or equivalent) who achieve Sustained Corticosteroid Control from Week 40 through Week 52
3. 3. Time to first BILAG flare over 52 weeks
4. 4. Proportion of participants who achieve Sustained SRI(4) response from Week 40 through Week 52
5. 5. Proportion of participants who achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52
6. 6. Proportion of participants who achieve SRI(4) at Week 24
7. 7. Proportion of participants who achieve clinical SRI(4) at Week 52
8. 8. Proportion of participants who achieve SRI(4) at Week 52 on low-dose corticosteroids
9. 9. Proportion of participants who achieve Lupus Low Disease Activity State (LLDAS) at Week 52
10. 10. Proportion of participants who achieve Definition of Remission in SLE (DORIS) at Week 52
11. 11. Change in Functional Assessment of Chronic Illness Therapy−Fatigue (FACIT-F) scale from baseline to Week 24 and from baseline to Week 52
12. 12. Change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain domain scale from baseline to Week 24 and from baseline to Week 52
13. 13. Change in SF-36 v2 Physical Component Summary scale from baseline to Week 24 and from baseline to Week 52
14. 14. Change in active joint count (swollen plus tender) from baseline to Week 24 and from baseline to Week 52
15. 15. Proportion of participants who achieve a ≥50% reduction in active joint counts (swollen plus tender) at each study visit
16. 16. Proportion of participants who achieve a ≥50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity (CLASI) Total Activity Score at each study visit, among Participants with CLASI Total Activity Score ≥10 at Baseline
17. 17. Proportion of participants who achieve sustained corticosteroid control from Week 40 through Week 52
18. 18. Cumulative corticosteroid use (in equivalent milligrams of prednisone) through Week 52
19. 19. Incidence and severity of adverse events
20. 20. Characterization of adverse events of special interest
21. 21. Change from baseline in targeted vital signs
22. 22. Change from baseline in targeted clinical laboratory test results
23. 23. Serum concentrations of obinutuzumab at specified timepoints
24. 24. Prevalence of ADAs at baseline and incidence of ADAs during the study

Investigational products

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

Test 1

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 9

Locations

5 EU/EEA countries · 24 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 8 files

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

Application history

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