Sequential Belimumab and T-cell Based Therapy in SLE

National University Health System (NUHS)

Status and phase: Enrolling; Phase 4

Conditions: Systemic Lupus Erythematosus

Treatments: Drug: Belimumab Injection [Benlysta]

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04447053

10743-SUBTLE

Details and patient eligibility

About

Systemic lupus erythematosus (SLE) is a disease in which the immune system (the bodily system that fights infection) attacks the body's own cells and tissues, causing inflammation and organ damage if not promptly and appropriately managed. Autoantibodies (specific proteins produced by the immune system which participate in attacking self tissues and organs) are the hallmarks of SLE which are produced by a specific type of white blood cells called B cells. Belimumab (Benlysta®) is a monoclonal antibody against the B cells by blocking the action of BLyS, a protein that prolongs the longevity and enhances the functions of B cells and is found to be elevated in patients with SLE, was approved by the FDA to treat patients with SLE. This study aims to study the effects of Belimumab on T cells, another specific type of white blood cells which also play a crucial role in SLE, in patients with SLE. In this trial, 80 adult patients with SLE will be recruited, 40 of them will be assigned to receive intravenous (IV) Belimumab with standard of care therapy (SOC), and 40 to receive SOC only. After 48 weeks of exposure to Belimumab + SOC and SOC alone, the phenotype and functions of T cells will be studied and compared.

Enrollment: 80 estimated patients

Sex: All

Ages: 21 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 21
2. Able to understand the details of the trial and willing to give written informed consent and comply with the requirements of the study protocol.
3. Patients who fulfill the classification criteria (SLICC 2012 or ACR 1997) for SLE and have active disease (SELENA-SLEDAI ≥ 6).
4. Patients whose sera are positive for ANA (titre ≥ 1:80) or anti-dsDNA (>100U/L based on NUH standard laboratory cut-off).
5. Patients who are on stable dose of prednisolone (0-40mg/day) and/or non-steroidal anti-inflammatory, antimalarial or immunosuppressive drugs for at least 30 days before first study dose.
6. Females of child-bearing potential and non-sterilized males with female partners of child-bearing potential may participate this trial only if they use a reliable means of contraception.
7. Females of child-bearing potential must have a negative serum pregnancy test within three weeks prior to baseline.

Exclusion criteria

1. They have severe active nephritis and/or active CNS lupus and/or other autoimmune diseases e.g. RA, mixed connective tissue disease, scleroderma, dermatomyositis and polymyositis.
2. They are pregnant.
3. They have had previous treatment with any B-cell and T-cell targeted biologic therapy, intravenous (IV) cyclophosphamide within 6 months of enrolment, intravenous immunoglobulins or prednisolone (>100mg/day) within 3 months.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Belimumab + SOC

Experimental group

Description:

Patients will be administered Belimumab, 10mg/kg, intravenously (IV) (together with SOC) in 1 hour on days 0, 14, and 28, and then every 28 days (4 weeks) until week 48.

Treatment:

Drug: Belimumab Injection [Benlysta]

SOC only

No Intervention group

Description:

Patients will receive SOC based on the discretion of attending physicians in accordance with the clinical disease manifestations of SLE and NUH practice of the treatment of SLE.