A multicenter, randomized 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)

The primary objective of this clinical trial is to compare the efficacy and safety of certolizumab pegol with the reference therapy belimumab in patients with moderately active or active systemic lupus erythematosus. This comparison is clinically relevant as it evaluates whether an alternative biologic therapy can provide comparable or superior disease control in patients with moderate to severe SLE activity, potentially expanding therapeutic options for this complex autoimmune disease.

The secondary objective is to assess the safety profile of the applied treatment regimen.

The sponsor did not provide information regarding the total number of participants for this clinical trial. The study population includes **adult patients** aged **18 to 65 years** with a documented diagnosis of **systemic lupus erythematosus (SLE)** according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria. Both **male and female subjects** are eligible to participate. Participants must present with at least **moderate SLE activity**, defined by a SELENA-SLEDAI score of ≥4 and a Physician Global Assessment of ≥1.0 on a scale of 0-3. The trial population requires positive **antinuclear antibody** immunofluorescence test results with a titer of at least 1:80, along with the presence of either **anti-double-stranded DNA antibodies** or **anti-Smith antibodies**. Patients may be receiving stable doses of conventional medications such as **azathioprine**, **methotrexate**, **mycophenolate mofetil**, **hydroxychloroquine**, **chloroquine**, or **leflunomide** for at least 8 weeks prior to screening. If **oral glucocorticosteroids** are used, the dose must not exceed 20 mg/day prednisone or equivalent and must remain stable for at least 2 weeks before the study. Female participants of childbearing potential must agree to use highly effective contraception methods throughout the study period and for several months following the last dose of study medication.

This is a multicenter, randomized clinical trial designed to compare the efficacy and safety of certolizumab pegol and belimumab in patients with moderate or severe activity of systemic lupus erythematosus. The study is classified as a Phase III clinical trial. The trial employs a comparative design in which certolizumab pegol serves as the test product and belimumab as the comparator. Both investigational medicinal products are administered via subcutaneous injection. Certolizumab pegol is provided as a solution for injection in pre-filled syringe with a maximum daily dose of 400 mg/ml and a maximum total dose of 400 mg/ml. Belimumab is available as a solution for injection in both pre-filled pen and pre-filled syringe formulations, with a maximum daily dose of 200 mg/ml and a maximum total dose of 200 mg/ml. The maximum treatment period for both products is 52 weeks.

The primary objective 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. The primary endpoint is the proportion of patients who achieved an SRI-4 response at Week 52, 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 score from baseline. Secondary endpoints include the percentage of patients achieving SRI-4 response at weeks 26 and 52 with concomitant glucocorticosteroid dose reduction to <10 mg/d, change from baseline in Physician Global Assessment of Disease Activity at week 52, change from baseline in the 36-Item Short Form Health Survey quality of life scale at week 52, percentage of patients achieving Lupus Low Disease Activity State at week 52, change from baseline in fatigue as measured by the FACIT fatigue score, change from baseline in tender and swollen joint counts at week 52, and reduction of skin lesions assessed according to the CLASI scale at week 52.

Eligible participants include patients aged 18-65 years with a documented diagnosis of systemic lupus erythematosus according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria. Patients must have at least moderate disease activity, defined as a SELENA-SLEDAI score ≥4 and Physician Global Assessment ≥1.0 on a scale of 0-3. Serological criteria include positive antinuclear antibody immunofluorescence test with a titer of at least 1:80 and presence of at least one of the following markers: antibodies against double-stranded DNA or anti-Smith antibodies. Patients may receive concomitant standard treatment with conventional medications such as azathioprine, methotrexate, mycophenolate mofetil, hydroxychloroquine, chloroquine, or leflunomide at specified doses, provided these doses have been stable for ≥8 weeks prior to the screening visit. If oral glucocorticosteroids are used, the dose must be ≤20 mg/day prednisone or equivalent and must be stable for at least 2 weeks prior to study entry. Patients of childbearing potential must agree to use highly effective contraception during the 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.

The estimated recruitment start date is October 1, 2025, with an estimated end date of January 31, 2030. Participant involvement in the study spans the entire treatment period of 52 weeks, with key assessment visits at weeks 26 and 52. The study protocol includes a screening visit to confirm eligibility, followed by randomization and initiation of treatment. Follow-up visits are scheduled throughout the 52-week treatment period to assess efficacy endpoints, safety parameters, and disease activity measures. The end-of-study visit occurs at week 52, at which time the primary and key secondary endpoints are evaluated. Conditions that may lead to early termination from the study are determined according to the study protocol and may include safety concerns, withdrawal of consent, protocol violations, or loss to follow-up.

The experimental treatment in this clinical trial is **certolizumab pegol**, administered as a **solution for injection in pre-filled syringe**. The active substance is certolizumab pegol with a concentration of **milligrams per millilitre**. The route of administration is via **subcutaneous injection**. The maximum daily dose is **400 milligrams per millilitre**, with a maximum total dose of **400 milligrams per millilitre**. The maximum treatment period is **52 weeks**.

The comparator treatment consists of **belimumab**, which is available in two pharmaceutical formulations: **solution for injection in pre-filled pen** and **solution for injection in pre-filled syringe**. The active substance is belimumab, a protein of other origin, with a concentration of **milligrams per millilitre**. The route of administration for both formulations is via **subcutaneous injection**. The maximum daily dose is **200 milligrams per millilitre**, with a maximum total dose of **200 milligrams per millilitre**. The maximum treatment period is **52 weeks**.

Efficacy will be assessed using the primary endpoint defined as the proportion of patients who achieved an SRI-4 response at Week 52. The SRI-4 response is characterized by a decrease of at least 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 less than 0.3) in the Physician Global Assessment (PGA) score from baseline.

Secondary efficacy endpoints include the percentage of patients achieving SRI-4 response at Week 52 with concomitant glucocorticosteroid dose reduction to less than 10 mg per day, and the percentage of patients achieving SRI-4 response at Week 26 with concomitant glucocorticosteroid dose reduction to less than 10 mg per day. Additional secondary endpoints comprise the change from baseline in Physician Global Assessment of Disease Activity (PGA) at Week 52, and the change from baseline in the 36-Item Short Form Health Survey (SF-36) Quality of Life Scale at Week 52. The percentage of patients achieving Lupus Low Disease Activity State (LLDAS) at Week 52 will also be evaluated, defined as SLEDAI-2k score of 4 or less with no disease activity in major organs, no new disease activity symptoms compared to previous assessment, physician's global assessment of activity of 1 or less on a 0-3 scale, current dose of glucocorticosteroids in prednisone equivalent of 7.5 mg per day or less, and well-tolerated standard treatment doses. Further secondary endpoints include the change from baseline in fatigue at Weeks 26 and 52 as measured by the FACIT fatigue score, change from baseline in tender joint count (from 28 joints) at Week 52, change from baseline in number of swollen joints (of 28 joints) at Week 52, and reduction of skin lesions assessed according to the CLASI scale at Week 52.