Randomized , double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of belimumab for early systemic lupus erythematosus

JRCT ID: jRCTs021210042

Registered date:14/10/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Systemic Lupus Erythematosus : SLE
• Date of first enrollment: 14/10/2021
• Target sample size: 30
• Study type: Interventional

Intervention(s)

Group A to which the test drug is administered and Group B to which the placebo is administered will be set.
Group A: In addition to the usual treatment, belimumab (GlaxoSmithKline Co., Ltd., trade name Benlysta) will be administered subcutaneously once a week at 200 mg. Administration will be continued for 24 weeks.
Group B: Placebo will be administered and standard of care will be performed.
Both groups will receive a combination of hydroxychloroquine unless there is a reason not to use hydroxychloroquine as usual treatment.
If the attending physician determines that it is not appropriate to administer the study drug, the attending physician will not administer the study drug during the week and will record the reason

Outcome(s)

• Primary Outcome: The distribution of LLDAS maintenance period over 48 weeks after the end of administration (from visit 5 to visit 9).

Secondary Outcome

1.% of subjects achieving LLDAS at 24 weeks after the end of administration
2.% of subjects achieving DORIS remission at Weeks 48 and 72weeks
3.Percentage of patients with recurrence at 24, 48, and 72 weeks (the SELENA-SLEDAI Flare Index [SFI])
4.Percentage of patients with normalized complement at 24 (Visit 5), 48 (Visit 7), and 72 (Visit 9) weeks
5.Percentage of patients with negative for anti-DNA antibodies at 24 (Visit 5), 48 (Visit 7), and 72 (Visit 9) weeks
6.Percentage of patients newly started on immunosuppressive drugs.
7.Percentage of patients who had their dose increased.
8.Percentage of the patients who start treatment with continuous oral corticosteroids throughout the entire study period.
9.Amount of change from baseline of SLEDAI-2K at 24 weeks (Visit
10.Rate of change from baseline of SLEDAI-2K at 24 weeks (Visit 5)
11.BICLA reaction rate at 24 weeks (Visit 5)
12.The incidence rates of various adverse events
13.Maintenance period of DORIS remission (off therapy, on therapy) between 24 and 72 weeks after the end of study drug administration.
14. The achievement rate of DORIS remission at 24 weeks (Visit5) after the end of administration
15.% of subjects achieving LLDAS at 48 (Visit7) and 72 (Visit9) weeks
16.% of subjects achieving LLDAS at 48 (Visit7) and 72 (Visit9) weeks in patients who did not receive immunosuppressive therapy (including belimumab)
17.% of subjects achieving DORIS remission at 48 (Visit7) and 72 (Visit9) weeks in patients who did not receive immunosuppressive therapy (including belimumab)
18.Change of QOL score from baseline using EQ-5D and Lupus PRO

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

1) Patients who have provided written consent for study participation.
2) Men and women who are at least 18 years old and under 80 years old at the time of obtaining consent.
3) Patients diagnosed with SLE. Diagnosis of SLE uses either ACR classification criteria (1997) or SLICC classification criteria (2012).
4) Patients who were diagnosed with SLE within the past 5 years.
5) Patients who can confirm any of the following immunological activities by clinical examination at screening: antinuclear antibody 80 times or more, anti-dsDNA antibody positive, low complement. Note that, it can be adopted if there is a result of one of those immunological activities performed within 28 days prior to obtaining consent.
6) Patients who have any of the following clinical symptoms related to SLE: joint symptoms, skin symptoms, mucous membrane symptoms, muscle symptoms, hair loss, general symptoms (fever, general malaise, weight loss), serositis

Exclude criteria

1) Patients who have used belimumab in the past.
2) Patients who have been administered corticosteroids (oral and IV) continuously within the 24 weeks before registration.
3) Patients who have undergone blood purification therapy (e.g., plasma exchange therapy, immunoadsorption therapy) within the 12 weeks before registration.
4) Patients who received new doses or increased doses of immunosuppressive drugs other than corticosteroids and cyclophosphamide pulse therapy within the 12 weeks before registration.
5) Patients who received cyclophosphamide pulse therapy within the 24 weeks before registration.
6) Patients who have administered biological products (anti-TNFalpha preparation, anti-IL6 receptor antibody, abatacept, anakinra, ustekinumab, anti-IL17 preparation) within the 12 weeks before registration.
7) Patients who received rituximab within the 12 months before registration.
8) Patients with severe active central nervous system symptoms (CNS lupus).
9) Patients with severe renal impairment (nephrotic syndrome, serum creatinine 2.5 mg/dL or more).
10) Patients with severe liver damage (decompensated liver damage).
11) Patients with unstable ischemic heart disease and heart failure.
12) Patients with malignant tumor complications or a history of it however, no recurrence for more than 5 years, patients with skin cancer that remained in the epithelium that has not recurred for more than 5 years, or cervical cancer that has not metastasized for more than 3 years may be included.
13) Patients who meet the following criteria for infectious diseases:
- Patients on continuous treatment for chronic infectious diseases
- Patients with a history of infectious disease requiring hospitalization within the 60 days before registration
- Patients who received antibiotics by parenteral administration within the 60 days before registration
14) HBs antigen positive, HIV positive, HCV positive, or HBV DNA PCR positive patients.
15) Patients with active tuberculosis.
16) Pregnant or lactating patients.
17) Refusal of abstinence or refusal/inability to use effective contraception during the study period
18) Patients who have participated in clinical trials or postmarketing clinical trials within the last 12 months.
19) Those who are allergic to hydroxychloroquine or belimumab
20) Patients who have attempted suicide within the 6 months before registration
21) Patients with primary immunodeficiency
22) Patients with hypo-IgG blood (IgG <400mg/dL)
23) Patients with IgA deficiency (IgA <10 </dL)
24) Patients with a history of alcoholism within the past year
25) Patients with a history of anaphylaxis to contrast agents or biologics
26) Patients with abnormal laboratory values whose clinical significance has been recognized by the investigator
27) Patients who are considered by the investigator to be inappropriate for inclusion in the study.
28) Person who received a live vaccine within 30 days before registration

Related Information

• Primary Sponsor: Ishii Tomonori
• Source(s) of Monetary Support: GlaxoSmithKline plc