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Sequential Belimumab and T-cell Based Therapy in SLE

Primary Purpose

Systemic Lupus Erythematosus

Status

Recruiting

Phase

Phase 4

Locations

Singapore

Study Type

Interventional

Intervention

Belimumab Injection [Benlysta]

About this trial

This is an interventional basic science trial for Systemic Lupus Erythematosus

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

National University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Belimumab + SOC

SOC only

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT04447053

First Posted

June 23, 2020

Last Updated

June 19, 2023

Sponsor

National University Hospital, Singapore

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT04447053

Brief Title

Sequential Belimumab and T-cell Based Therapy in SLE

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 8, 2021 (Actual)

Primary Completion Date

May 20, 2025 (Anticipated)

Study Completion Date

May 20, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National University Hospital, Singapore

Collaborators

GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Systemic Lupus Erythematosus

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Belimumab + SOC

Arm Type

Experimental

Arm 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.

Arm Title

SOC only

Arm Type

No Intervention

Arm 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.

Intervention Type

Drug

Intervention Name(s)

Belimumab Injection [Benlysta]

Intervention Description

Belimumab, IV infusion, 10mg/kg on days 0, 14, 28 then every 28 days until week 48.

Primary Outcome Measure Information:

Title

Comparing the ratio of Treg/Teff in Belimumab + SOC arm with SOC-only arm

Description

Time Frame

Baseline, week 4, week 12, week 24, week 36, week 48 and week 60

Title

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

Description

TCR sequencing and RNA expression with the use of the state-of-the-art 10x Genomic nano-droplet technology.

Time Frame

up to week 48

Secondary Outcome Measure Information:

Title

To compare the numeric difference in other T cell subsets (Th1, Th2 and Th17) between the 2 arms

Description

The enumeration of T-cell subsets by multi-color flow cytometry.

Time Frame

Baseline, week 4, week 12, week 24, week 36, week 48 and week 60

Title

To compare the potential improvement of cognitive function between the 2 arms

Description

Time Frame

Baseline and week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anselm Mak

Phone

+6567722598

mdcam@nsu.edu.sg

First Name & Middle Initial & Last Name or Official Title & Degree

Nien Yee Kow

Phone

+6566015194

mdckown@nus.edu.sg

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anselm Mak

Organizational Affiliation

National University Hospital, Singapore

Official's Role

Principal Investigator

Facility Information:

Facility Name

National University Hospital

City

SIngapore

Country

Singapore

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anselm Mak

Phone

+6567722598

mdcam@nus.edu.sg

12. IPD Sharing Statement

Learn more about this trial

Sequential Belimumab and T-cell Based Therapy in SLE

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