Steroid-Independent protocol using BELImumab for disease flare in patients with systemic lupUS erythematosus

JRCT ID: jRCTs011190011

Registered date:13/03/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Systemic lupus erythematosus
• Date of first enrollment: 17/11/2020
• Target sample size: 48
• Study type: Interventional

Intervention(s)

Subjects who have met the entry criteria will be randomly to one of the two treatment groups based on a computer-generated randomization schedule as follows: 1) BEL group and 2) CS increased group using standard CS therapy (CS group) .

1. Subjects in BEL group will receive BEL 200 mg weekly SC on Day 0, and then every 7 days through week 24 or BEL 10mg/kg IV on Day 0, 14, 28 and every 1 month.
2. Subjects in CS group will receive prednisolone (</= 0.4mg/kg/day, maximum 20 mg/day) or equivalent dose for a maximum of 2 weeks followed by steroid tapering schedule according to the ACR Ad hoc working group on steroid-sparing criteria in Lupus and The British Society for Rheumatology guideline for the management of SLE in adults.
All subjects will start treatment with MMF oral 1g/day
In both groups, if subjects are not on treatment with HCQ, their drug will be started at a dose individually adjusted on basis of the patient's height (from 200 to 400mg/day).
In the BEL group, the baseline dose of CS </= 7.5mg/day at screening could not be further increased.

Outcome(s)

Primary Outcome

All adverse events (AES) and all serious adverse events (SAES) (reported throughout the 12-weeks of treatment.

AES include:
Any new AES not present at Day 0
OR
any increase in severity grade of signs, symptoms, or laboratory abnormalities
OR
any SAES

Secondary Outcome

1)Efficacy at 12 and 24 weeks
2)Safety at 12 and 24 weeks

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Patients aged 18 or over with SLE diagnosis according to the ACR revised classification criteria
2. Repeat seropositive for ANA and/or anti-dsDNA antibody
3. Non-severe SLE flares (mild or moderate)
1) SELENA-SLEDAI score of >/= 6 points or >/= 1 BILAG 2004 index level B
2) Treatment with low dose CS (Corticosteroid, prednisolone (PSL) or equivalent </= 7.5 mg/day
3) Are on a stable SLE therapy for at least 30 days prior to Day 0

Exclude criteria

1. Severe organ threatening SLE
1) severe active lupus nephritis (>3 g/gCre proteinuria using spot urine protein to creatinine ratio, or serum
creatinine > 2.5 mg/dL)
2) severe active neuropsychiatric SLE
2. Pregnancy or lactation
3. Are on treatment with > 7.5 mg/day of prednisolone at Day 0
4. Required > 20 mg/day prednisolone or equivalent over 2 weeks after the first dose of study medication.
5. Have background treatment with belimumab (BEL).
6. Have maculopathy and visual field defect.
7. Have any conditions that cannot use mycophenolate mofetil (MMF) or hydroxychloroquine HCQ.
8. Have an active infection
9. Infection history
1) Currently on any suppressive therapy for a chronic infection
2) Hospitalization for treatment of infection within 60 days of Day 0.
3) Use of parenteral (IV or IM) antibiotics (anti-bacterial, antiviral, anti-fungal, or anti-parasitic agents) within 60 days of Day 0.
10. Have the following excluded concomitant medications
1) Anti-B-cell therapy
Wash-out of 5 therapeutic half-lives after prior B-cell therapy, or until pharmacodynamic effect would be minimal (e.g., 1 year following rituximab)
2) 90 days prior to BEL:
Intravenous cyclophosphamide
Intravenous immunoglobulins
3) 30 days prior to BEL (or 5 half-lives, whichever is greater)
Any biologic or non-biologic investigational agent
4) Live vaccines within 30 days prior to baseline or concurrently with BEL
5) Other medications, including HCQ, should be maintained at the same dose prior to BEL.

Related Information

• Primary Sponsor: Atsumi Tatsuya
• Source(s) of Monetary Support: GlaxoSmithKline plc