Systemic Lupus ErythematosusPhase 4NCT04447053
Sequential Belimumab and T-cell Based Therapy in SLE
A Phase 4 study testing Belimumab Injection [Benlysta] in people with Systemic Lupus Erythematosus, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Belimumab Injection [Benlysta]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteSingapore
- Study dates
- 8 Nov 2021to 20 May 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 21
- Able to understand the details of the trial and willing to give written informed consent and comply with the requirements of the study protocol.
- Patients who fulfill the classification criteria (SLICC 2012 or ACR 1997) for SLE and have active disease (SELENA-SLEDAI ≥ 6).
- Patients whose sera are positive for ANA (titre ≥ 1:80) or anti-dsDNA (>100U/L based on NUH standard laboratory cut-off).
- 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.
- 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.
- Females of child-bearing potential must have a negative serum pregnancy test within three weeks prior to baseline.
Who cannot join
- 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.
- They are pregnant.
- 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 locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore
Anselm Mak, +6567722598, mdcam@nus.edu.sg
About this study
Official title: Sequential Belimumab Followed by T-cell Based Therapy in the Treatment of Systemic Lupus Erythematosus (SUBTLE) - a Preliminary Proof-of-concept Mechanistic Study
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.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Belimumab Injection [Benlysta]
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belimumab Injection [Benlysta]Drug
Belimumab, IV infusion, 10mg/kg on days 0, 14, 28 then every 28 days until week 48.
| Study group | Role | What they receive |
|---|---|---|
| Belimumab + SOC | Experimental | 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. Receives: Drug: Belimumab Injection [Benlysta] |
| SOC only | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparing the ratio of Treg/Teff in Belimumab + SOC arm with SOC-only arm
The enumeration of T-cell subsets by multi-color flow cytometry including Th1 (CD4+Tbet+), Th2 (CD4+GATA3+), Th17 (CD4+RoRgamat+) and Treg (CD4+CD25+FoxP3+) cells, as well as CD19+CD20+ B cells after staining with respective fluorescent-conjugated antibodies.
Measured: Baseline, week 4, week 12, week 24, week 36, week 48 and week 60
Identifying and comparing the TCR sequence of the variable regions (CDR1, CDR2 and CDR3) and their RNA expression profile before and after 48 weeks of Belimumab therapy
TCR sequencing and RNA expression with the use of the state-of-the-art 10x Genomic nano-droplet technology.
Measured: up to week 48
Secondary outcomes (2)
To compare the numeric difference in other T cell subsets (Th1, Th2 and Th17) between the 2 arms
The enumeration of T-cell subsets by multi-color flow cytometry.
Measured: Baseline, week 4, week 12, week 24, week 36, week 48 and week 60
To compare the potential improvement of cognitive function between the 2 arms
The use of the computerized Automated Neuropsychological Assessment Matrix (ANAM) which serves as an initial screening tool to pick up subtle cognitive dysfunction in healthy populations and serial assessments to track the progress of cognitive dysfunction in SLE patients over time.
Measured: Baseline and week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start8 Nov 2021
- Primary completion20 May 2025 (estimated)
- Study completion20 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Anselm Mak, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04447053
- Sponsor's protocol ID
- 10743-SUBTLE
- Status last verified
- Jun 2023
- First submitted
- 23 Jun 2020
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential Belimumab Followed by T-cell Based Therapy in the Treatment of Systemic Lupus Erythematosus (SUBTLE) - a Preliminary Proof-of-concept Mechanistic Study
- ClinicalTrials.gov ID
- NCT04447053
- Acronym / sponsor ID
- 10743-SUBTLE
- Conditions
- Systemic Lupus Erythematosus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 8 Nov 2021 (actual)
- Primary completion
- 20 May 2025 (estimated)
- Study completion
- 20 May 2025 (estimated)
- First posted
- 25 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Belimumab + SOC | Experimental | Drug: Belimumab Injection [Benlysta]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. |
| SOC only | No intervention | –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. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 21
- Able to understand the details of the trial and willing to give written informed consent and comply with the requirements of the study protocol.
- Patients who fulfill the classification criteria (SLICC 2012 or ACR 1997) for SLE and have active disease (SELENA-SLEDAI ≥ 6).
- Patients whose sera are positive for ANA (titre ≥ 1:80) or anti-dsDNA (>100U/L based on NUH standard laboratory cut-off).
- 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.
Key exclusion criteria (3 listed)
- 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.
- They are pregnant.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Belimumab Injection [Benlysta]Belimumab, IV infusion, 10mg/kg on days 0, 14, 28 then every 28 days until week 48. | Drug | Belimumab + SOC |
Primary outcome
Comparing the ratio of Treg/Teff in Belimumab + SOC arm with SOC-only arm
Time frame: Baseline, week 4, week 12, week 24, week 36, week 48 and week 60
The enumeration of T-cell subsets by multi-color flow cytometry including Th1 (CD4+Tbet+), Th2 (CD4+GATA3+), Th17 (CD4+RoRgamat+) and Treg (CD4+CD25+FoxP3+) cells, as well as CD19+CD20+ B cells after staining with respective fluorescent-conjugated antibodies.
Identifying and comparing the TCR sequence of the variable regions (CDR1, CDR2 and CDR3) and their RNA expression profile before and after 48 weeks of Belimumab therapy
Time frame: up to week 48
TCR sequencing and RNA expression with the use of the state-of-the-art 10x Genomic nano-droplet technology.
2 secondary outcomes
To compare the numeric difference in other T cell subsets (Th1, Th2 and Th17) between the 2 arms
Time frame: Baseline, week 4, week 12, week 24, week 36, week 48 and week 60
To compare the potential improvement of cognitive function between the 2 arms
Time frame: Baseline and week 52
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anselm Mak principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Belimumab Injection [Benlysta] in people with Systemic Lupus Erythematosus, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anselm Mak (+6567722598, mdcam@nsu.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparing the ratio of Treg/Teff in Belimumab + SOC arm with SOC-only arm (time frame: Baseline, week 4, week 12, week 24, week 36, week 48 and week 60). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.