Clinical trial comparing the efficacy and safety of certolizumab pegol and belimumab in patients with moderate or severe activity of systemic lupus erythematosus (CERT-SLE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-10-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Agencja Badań Medycznych

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The purpose of the study is to compare the efficacy and safety of treatment with certolizumab pegol with the reference therapy belimumab in patients with moderately active or active systemic lupus erythematosus (SLE).

Secondary objectives 1

1. Assessment of the applied treatment's safety

Conditions and MedDRA coding

moderate or severe activity of systemic lupus erythematosus (SLE)

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Signed informed consent form
2. Age 18-65 years
3. Ability to follow the study protocol
4. Documented diagnosis of SLE according to the American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) classification criteria at any time before or during screening
5. Positive antinuclear antibody (ANA) immunofluorescence test result with a titer of at least 1:80 AND Presence of at least one of the following serological markers of SLE at screening: ● Antibodies against double-stranded DNA (anti-dsDNA); OR ● Anti-Smith antibodies (anti-Sm)
6. At least moderate SLE activity, defined as meeting all of the following criteria: ● SELENA-SLEDAI score ≥4 indicating active disease ● Physician Global Assessment (PGA) ≥1.0 (on a scale of 0-3)
7. Acceptable medications and doses: ● Azathioprine: 1 to 2.5 mg/kg/day ● Methotrexate: 7.5 to 25 mg/week ● Mycophenolate mofetil: 500 to 3000 mg/day ● Hydroxychloroquine: 200 to 400 mg/day ● Chloroquine: 250 to 500 mg/day ● Leflunomide - 10-20 mg/day Patients treated with conventional medications should be on stable doses for ≥ 8 weeks prior to screening visit
8. Patients may receive standard treatment but no new therapy has been initiated or therapy has been withdrawn in the 8 weeks prior to the screening visit
9. If oral glucocorticosteroids (GCS) are used, the dose must be ≤20 mg/day prednisone (or equivalent) and must be stable for at least 2 weeks prior to study
10. Patients of childbearing potential should agree to abstinence or use a highly effective method of contraception during the entire study period and for at least 5 months after the last dose of certolizumab pegol or at least 4 months after the last dose of belimumab

Exclusion criteria 26

1. Pregnancy or breastfeeding
2. Patients who have ever received any of the study drugs in the past
3. Patients who received any of the following medications and/or procedures during the indicated time period: ● Plasmapheresis or intravenous immunoglobulin within the last 12 weeks prior to screening ● Lymphatic depleting therapy. B (e.g., anti-CD20 or anti-CD19) within 24 weeks prior to screening ● blisibimod, tabalumab (or other anti-B cell activating factor [BAFF] agents), atacicept, epratuzumab (or other anti-CD22 agents) within 5 half-lives or 12 weeks (whichever is longer) prior to screening ● cyclophosphamide or other alkylating agents within 12 weeks prior to screening ● oral cyclosporine, anakinra, tacrolimus, sirolimus, or other calcineurin inhibitors, topical calcineurin inhibitors within 4 weeks prior to screening ● thalidomide or thalidomide derivatives within 24 weeks prior to screening ● tumor necrosis factor (TNF) antagonists, tocilizumab or other biologics not listed previously used in the past. ● Any other immunosuppressive drug used for SLE not listed in the inclusion criteria within 12 weeks or 5 half-lives prior to screening, whichever is longer
4. Patients with active lupus nephritis: ● Proteinuria > 2 g/24 h or equivalent based on albumin/creatinine ratio (ACR) ● Active proliferative lupus nephritis (class III or IV TZN) based on renal biopsy performed within 6 months prior to screening (or during the study). ● Hemodialysis or high-dose corticosteroids (>100 mg/d prednisone or equivalent) for lupus erythematosus renal disease within 90 days of screening ● Serum creatinine > 2.0 mg/dL or estimated glomerular filtration rate ≤ 30 mL/min or chronic renal replacement therapy
5. Severe active central nervous system lupus erythematosus within 52 weeks of screening
6. Major surgery within 8 weeks prior to screening
7. Rheumatic disease other than systemic lupus erythematosus (rheumatoid arthritis, mixed connective tissue disease, systemic sclerosis) acceptable diagnosis of secondary Sjögren's syndrome
8. Immunization with a live or attenuated vaccine within 4 weeks prior to planned treatment
9. Known hypersensitivity to human, humanized or mouse monoclonal antibodies
10. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) >2 x ULN, if normalization occurs the patient may be considered for a repeat screening visit
11. Bilirubin >1.5 x GGN
12. History of severe bronchial asthma or other clinically significant pulmonary abnormalities
13. NYHA III/IV cardiovascular disease
14. Previous stroke, heart attack within 6 months prior to screening
15. Patients with chronic liver disease (Child Pugh A, B, C liver dysfunction)
16. Active or significant history of infection, including treatment with intravenous antibiotics in the last 4 weeks or oral antibiotics in the 2 weeks prior to screening
17. A positive SARS-CoV-2 test result during visit “0” is an exclusion criterion, while an infection more than 4 weeks before screening and confirmed by a negative SARS-CoV-2 test is not an exclusion criterion
18. Active confirmed tuberculosis or latent without chemoprophylaxis performed in accordance with applicable local recommendations
19. Active HBV, HCV infection (acceptable history of HCV after treatment and virus elimination confirmed by PCR test)
20. Human immunodeficiency virus (HIV) infection
21. Diagnosed primary or secondary immunodeficiency
22. Active or past malignancy within 5 years prior to screening, except resected/cured localized basal cell or squamous cell carcinoma of the skin or cervical cancer in situ
23. Hypogammaglobulinemia (IgG <400 mg/dl) or IgA (IgA <10 mg/dl) deficiency
24. Active or past drug or alcohol abuse
25. History of severe depression
26. The inability to understand and comply with the protocol requirements (lack of compliance) also excludes from participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients who achieved an SRI-4 response defined as a decrease of ≥ 4 points on the SELENA-SLEDAI scale, no new BILAG A organ score and no more than 1 new BILAG B score, and no worsening (increase < 0.3) in the Physician Global Assessment (PGA) score from baseline at Week 52

Secondary endpoints 9

1. Percentage of patients achieving SRI-4 response at week 52 with concomitant glucocorticosteroid dose reduction to <10 mg/d
2. Percentage of patients achieving SRI-4 response at week 26 with concomitant glucocorticosteroid dose reduction to <10 mg/d
3. Change from baseline in Physician Global Assessment of Disease Activity (PGA) at week 52
4. Change from Baseline in the 36-Item Short Form Health Survey (SF-36) Quality of Life Scale at Week 52
5. Percentage of patients achieving LLDAS (Lupus Low Disease Activity State) at week 52, defined as: ● SLEDAI-2k ≤4 and no disease activity in major organs (kidneys, central nervous system [CNS], heart, lungs), no vasculitis, fever, hemolytic anemia, gastrointestinal activity ● no new disease activity symptoms compared to previous assessment ● physician's global assessment of activity phPGA ≤1 on a 0-3 scale ● current dose of glucocorticosteroids in prednisone equivalent ≤7.5 mg/day ● well-tolerate
6. Change from baseline in fatigue at weeks 26 and 52 as measured by the FACIT fatigue score
7. Change from baseline in tender joint count (from 28 joints) at week 52
8. Change from baseline in number of swollen joints (of 28 joints) at week 52
9. Reduction of skin lesions assessed according to the CLASI scale at week 52

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Sponsor organisation

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Address

Ul. Spartanska 1

City

Warsaw

Postcode

02-637

Country

Poland

Scientific contact point

Organisation

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Contact name

Centrum Wsparcia Badań Klinicznych

Public contact point

Organisation

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Contact name

Centrum Wsparcia Badań Klinicznych

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

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

Application history

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