A Study to Evaluate the Efficacy and Safety of BIIB059 (Litifilimab) in Adult Participants With Active Systemic Lupus Erythematosus Receiving Background Nonbiologic Lupus Standard of Care (TOPAZ-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biogen Idec Research Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

30 Nov 2021 → ongoing

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Biogen Idec Research Limited

External identifiers

EU CT number

2023-505695-30-00

EudraCT number

2020-005775-12

ClinicalTrials.gov

NCT04895241

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Others, Pharmacodynamic

The primary objective of this study is to demonstrate efficacy of litifilimab compared with placebo in participants with active systemic lupus erythematosus (SLE), who are receiving background lupus standard of care (SOC) therapy in reducing disease activity.

Secondary objectives 10

1. To demonstrate efficacy of litifilimab compared with placebo in participants with active SLE, who are receiving background lupus SOC therapy in reducing disease activity
2. To demonstrate organ-specific efficacy of litifilimab compared with placebo in participants with active SLE, who are receiving background lupus SOC therapy in reducing joint disease activity
3. To demonstrate effect of litifilimabcompared with placebo in reducing OCS 3 use
4. To demonstrate organ-specific efficacy of litifilimab compared with placebo in participants with active SLE, who are receiving background lupus SOC therapy in reducing skin disease activity
5. To demonstrate efficacy of litifilimab compared with placebo in participants with active SLE, who are receiving background lupus SOC therapy in reducing occurrence of flare up to Week 52"
6. To evaluate additional efficacy of litifilimab compared with placebo in reducing disease activity with additional disease activity measures
7. To evaluate the effect of litifilimab compared with placebo in reducing OCS 3 use
8. To assess the difference between litifilimab and placebo on participant-reported HRQoL, symptoms, and impacts of SLE
9. To evaluate the safety and tolerability of litifilimab in participants with active SLE
10. To evaluate immunogenicity of litifilimab in participants with active SLE

Conditions and MedDRA coding

systemic lupus erythematosus

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

In accordance with Biogen’s Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/ Supporting Information: Time Frame: Access Criteria: URL: https://vivli.org/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participant must be diagnosed with systemic lupus erythematosus (SLE) at least 24 weeks prior to screening and must meet the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria for SLE at screening by a qualified physician.
2. Participant has a modified Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score ≥ 6 (excluding alopecia, fever, lupus-related headache, and organic brain syndrome) at screening (adjudicated).
3. Participant has a modified clinical SLEDAI-2K score ≥ 4 (excluding anti-dsDNA, low complement component 3 (C3) and/or complement component 4 (C4), alopecia, fever, lupus-related headache, and organic brain syndrome) at Screening (adjudicated) and randomization.
4. Participant has BILAG-2004 grade A in ≥ 1 organ system or BILAG-2004 grade B in ≥ 2 organ systems at Screening (adjudicated) and randomization.
5. Participant must be treated with one of the following background nonbiologic lupus SOC therapies, initiated ≥ 12 weeks prior to Screening and at stable dose ≥ 4 weeks prior to randomization, a. Antimalarials as stand-alone treatment b. Antimalarial treatment in combination with OCS and/or a single immunosuppressant c. Treatment with OCS and/or a single immunosuppressant

Exclusion criteria 9

1. History of or positive test result for human immunodeficiency virus (HIV).
2. Current hepatitis C infection (defined as positive hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid [RNA]).
3. Current hepatitis B infection (defined as positive for HBsAg and/or positive for total anti- HBc) with positive reflex HBV DNA).
4. Presence of uncontrolled or New York Heart Association class III or IV congestive heart failure. - Active severe lupus nephritis where, in the opinion of the Investigator, protocol-specified SOC is insufficient and use of a more aggressive therapeutic approach is indicated, such as adding IV cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol is indicated; or urine protein-creatinine ratio > 2.0 or severe chronic kidney disease (estimated glomerular filtration rate < 30 milliliters per minute per 1.73 meter square [mL/min/1.73 m^2]) calculated using the abbreviated modification of diet in renal disease equation.
5. Any active skin conditions other than cutaneous lupus erythematosus (CLE) that may interfere with the study assessment of CLE such as but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE skin lupus manifestation or drug-induced lupus.
6. History or current diagnosis of a clinically significant non-SLE-related vasculitis syndrome.
7. Active neuropsychiatric SLE
8. Use of oral prednisone (or equivalent) above 20 mg/day.
9. Other protocol defined Exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of Participants Who Achieved a Systemic Lupus Erythematosus Responder Index of 4 (SRI-4) Response at Week 52.

Secondary endpoints 33

1. Percentage of Participants Who Achieved a BICLA Response at Week 52
2. Percentage of Participants With at Least 4 Joints (Both Swollen and Tender) at Baseline Who Achieved a Joint-50 Response at Week 52
3. Percentage of Participants with OCS ≥10 milligrams per day (mg/day) at Baseline with OCS Reduction to ≤7.5 mg/day at Week 40, Which Is Sustained Through Week 52 with No Disease Worsening from Week 40 to Week 52
4. Percentage of Participants with a CLASI-A score ≥10 at Baseline Who Achieved a 50% Improvement From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity Score (CLASI50) Response at Week 24
5. Annualized Flare Rate Through Week 52
6. Change from Baseline in Physician's Global Assessment (PGA) Visual Analog Scale (VAS) Score by Visit
7. Percentage of Participants Who Achieved a British Isles Lupus Activity Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response by Visit
8. Time to Onset of SRI-4 Response Sustained Through Week 52
9. Percentage of Participants Who Achieved SRI-4, -5, or -6 Response by Visit
10. Percentage of Participants with Joint-50 Response by Visit
11. Percentage of Participants with Baseline CLASI-A Score ≥10 Who Achieved a CLASI-20, -50, -70, or -90 Response by Visit
12. Percentage of Participants with Baseline CLASI-A Score ≥10 Who Achieved a CLASI-A Score of ≤ 1 by Visit
13. Time to First British Isles Lupus Activity Group-2004 (BILAG-2004) Severe Flare by Visit
14. Time to First Severe Flare as defined by the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index Flare Index (SFI)
15. Percentage of time spent in LLDAS.
16. Proportion of participants with sustained LLDAS as defined by the number of participants with ≥ 3, ≥ 5, and ≥ 7 consecutive visits in LLDAS up to and including Week 52.
17. Proportion of participants who achieved LLDAS at Week 52.
18. Percentage of Participants With Baseline OCS ≥10 mg/day Who Achieved ≤7.5 mg/day at Week 52
19. Change from Baseline in Lupus-Specific Health-Related Quality-ofLife Questionnaire (LupusQoL) Score
20. Change From Baseline in Short Form Health Survey-36 (SF-36) Score
21. Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score
22. Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Score
23. Change From Baseline in Work Productivity and Activity Impairment (WPAI): Lupus Score
24. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
25. Number of Participants with Antibodies to litifilimab
26. Percentage of Participants with severe flares through Week 52
27. Proportion of participants who achieved SLEDAI-2K improvement at Week 52.
28. Proportion of participants who achieved no worsening of BILAG at Week 52.
29. Proportion of participants who achieved no worsening of PGA-VAS at Week 52.
30. Proportion of participants who achieved no worsening of SLEDAI-2K at Week 52.
31. Proportion of participants who achieved BILAG improvement at Week 52.
32. Proportion of participants with OCS ≥ 10 mg/day at Baseline with OCS reduction to ≤ 5 mg/day at Week 40, which is sustained through Week 52 with no disease worsening5 from Week 40 to Week 52.
33. Proportion of participants with OCS ≥ 7.5 mg/day at Baseline with OCS reduction to ≤ 7.5 mg/day at Week 52.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biogen Idec Research Limited

Sponsor organisation

Biogen Idec Research Limited

Address

Building 5 Foundation Park, Roxborough Way Roxborough Way

City

Maidenhead

Postcode

SL6 3UD

Country

United Kingdom

Scientific contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Public contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Third parties 13

Locations

6 EU/EEA countries · 36 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 163 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