UMIN-CTR Clinical Trial

Public title

Glucocorticoid-tapering aimed maintenance therapy in patients with systemic lupus erythematosus

Acronym

BLISS-POST

Scientific Title

Glucocorticoid-tapering aimed maintenance therapy in patients with systemic lupus erythematosus

Scientific Title:Acronym

BLISS-POST

Region

Japan

Condition

systemic lupus erythematosus

Classification by specialty

Clinical immunology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

This study is a clinical trial aiming to taper and discontinue glucocorticoid (GC) using belimumab in patients with systemic lupus erythematosus (SLE) and low disease activity. Following induction therapy, at least 3 years of immunosuppressive maintenance treatment is recommended to optimize outcomes and lupus maintenance treatment should aim for the lowest glucocorticoid dosage needed to control disease, and if possible.
On the other hand, accumulated evidence indicates the good safety and efficacy profile of belimumab in SLE for the maintenance therapy. Also, belimumab reduces serum soluble BAFF concentrations and thereby allows autoimmune B cells to undergo apoptosis, preventing escape and proliferation of new or existing autoimmune B-cell clones. We, therefore, have hypothesized that by the use of belimumab, the tapering of GC in patients with maintenance phase of SLE.
Within this context, this study is conducted with the goal of discontinuation of GC using belimumab for the maintenance phase of SLE treatments. In addition, peripheral blood immune phenotype, biomarkers, and autoantibodies will be evaluated to identify patients who will be able to withdraw GC. The result of study will not only reveal the appropriate treatment for lupus SLE patients after achieving remission, but also contribute to improvement of economic problems including reduction of medical expenses. If this study worked well, enormous benefit and flexibilitiy would be brought to many patients with SLE and other autoimmune diseases who are treated with GC.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Proportion of subjects who achieve glucocorticoid free [Time Frame: Week 52]

Key secondary outcomes

Secondary endpoints
1) Score of SELENA-SLEDAI [Time Frame: Week 24 and 52]
2) Mean changes from baseline in Physician's Global Assessment (PGA) using visual analogue scale (VAS) [Time Frame: Week 24 and 52]
3) Mean dose of glucocorticoids (Last Observation Carried Forward)
4) Annualized flare rate with flare defined as SELENA - SLEDAI score > 4 points [Time Frame: Week 52]

Exploratory endpoints
1) The mean duration, subjects achieve 50% dose reduction of glucocorticoid [Time Frame: Week 52]
2) The immunophenotype of peripheral blood by flow cytometric analysis [Time Frame: Week 52]
3) The differences of immunophenotype, biomarkers, and autoantibodies between the patients who could achieve glucocorticoid free and the patients who could not achieve glucocorticoid free [Time Frame: Week 52]

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

a) Diagnosed as SLE by American College of Rheumatology (ACR) classification criteria.
b) Patients who have low disease activity (SELENA-SLEDAI < 4 points)
c) Receipt of low dose GC (no more than prednisolone equivalent 10 mg) over 30 days
d) Receipt of HCQ and/or other immunosuppressive drug such as Azathioprine and MMF over 30 days.

Key exclusion criteria

a) Patients who contraindicated by package insert of BLM.
b) Receipt of B cell depleted therapy (biologic agent) within 1 year.
c) Receipt of cyclophosphamide (Endoxan) within 6 months.
d) Receipt of high dose GC (prednisolone equivalent 1mg/kg) within 6 months.
e) Receipt of plasma exchange within 6 months.
f) Have developed clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases).
g) Have developed any other medical diseases (e.g., cardiopulmonary), laboratory abnormalities, or conditions (e.g., poor venous access) that in the opinion of the principal investigator, makes the subject unstable for the study.

Target sample size

100

Name of lead principal investigator

1st name
Middle name
Last name	Yoshiya Tanaka

Organization

School of Medicine, University of Occupational and Environmental Health, Japan

Division name

First Department of Internal Medicine

Zip code

Address

1-1, Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan

TEL

093-603-1611

Email

tanaka@med.uoeh-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Satoshi Kubo

Organization

School of Medicine, University of Occupational and Environmental Health, Japan

Division name

First Department of Internal Medicine

Zip code

Address

1-1, Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan

TEL

093-603-1611

Homepage URL

Email

kubosato@med.uoeh-u.ac.jp

Institute

First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan

Institute

Department

Personal name

Organization

Self funding

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

03

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2018

Year

01

Month

01

Day

Date of IRB

Anticipated trial start date

2018

Year

03

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Every patient will start belimumab (intravenous) in addition to each current therapy. Then, concomitant GC will be reduced by half at week 8. At week 16, the dose of GC will be reduced by quarter. Thereafter, the patients will withdraw the concomitant GC at week 24 (For details of the test, see the figure below).

The disease activity will be evaluated regularly. The disease activity will be evaluated regularly. If the disease activity exacerbates (SELENA - SLEDAI score > 4 points) or judges that the attending doctor should stop the trial, the patients be withdrawn this clinical trial immediately. In that case, the dose of GC will be restored. However, further increase and addition of other medicines are also possible at the discretion of the attending physician.

In this study, immunophenotype of peripheral blood will be analysed by flow cytometry at baseline, week 24, and week 52.

Registered date

2018

Year

02

Month

12

Day

Last modified on

2018

Year

02

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035689