Efficacy and Safety of Belimumab in SLE Patients

• ClinicalTrials.gov Identifier: NCT04515719
• Recruitment Status: Not yet recruiting
• First Posted: August 17, 2020
• Last Update Posted: August 18, 2020
• Sponsor: RenJi Hospital
• Information provided by (Responsible Party): RenJi Hospital

Study Description

Brief Summary:

Systemic lupus erythematosus (SLE) is a chronic inflammatory systemic autoimmune disease. Recurrent relapses of disease and development of long-term organ damage are two key unsolved clinical problems. Belimumab is the only FDA-approved biological agent for SLE. Data showed that treatment with belimumab on the background of standard therapy was effective in active SLE patients. However, the efficacy of low-dose belimumab for prevention of disease flares in SLE patients with low disease activity is to be explored.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Biological: Belimumab; Biological: Placebo	Phase 4

Detailed Description:

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with the incidence of about 70/100,000 in China. Recurrent relapses of disease and development of long-term organ damage are two key unsolved clinical problems. Its pathogenesis is still unclear, but B cells have been confirmed to play a vital role in it. Belimumab, a B-lymphocyte stimulating factor (Blys) inhibitor, was the only FDA-approved biological agent for SLE. BLISS-52 showed that more active lupus patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 10 mg/kg (58% vs 46%, p=0·0024) than with placebo. But there was limited data about belimumab in SLE patients with low disease activity. Our previous study indicated that even these patients still have an annual flare rate of 30-40%. Therefore, we try to explore whether low-dose of belimumab could prevent the disease flares in SLE patients with low disease activity.

Study Design

• Study Type: Interventional
• Estimated Enrollment: 334 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Efficacy and Safety of Belimumab for Prevention of Disease Flares in SLE Patients With Low Disease Activity
• Estimated Study Start Date: November 1, 2020
• Estimated Primary Completion Date: March 1, 2023
• Estimated Study Completion Date: June 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Belimumab 2mg/kg; Eligible patients were randomized in a 1:1 ratio to belimumab/placebo on the background of standard therapy. Belimumab 2mg/kg is administered intravenously at week 0, week 2, week 4 and then every 4 weeks until 48 weeks.	Biological: Belimumab; Belimumab 2mg/kg intravenously; Other Name: BENLYSTA™
Placebo Comparator: Placebo; Eligible patients were randomized in a 1:1 ratio to belimumab/placebo on the background of standard therapy. Placebo (normal saline) is administered intravenously at week 0, week 2, week 4 and then every 4 weeks until 48 weeks.	Biological: Placebo; Placebo intravenously

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with disease flares [ Time Frame: 52 weeks ]
   Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI).

Secondary Outcome Measures :

1. Percentage of patients with mild/moderate flares [ Time Frame: 52 weeks ]
   Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI).
2. Percentage of patients with major flares [ Time Frame: 52 weeks ]
   Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI).
3. Time to first disease flare [ Time Frame: 52 weeks ]
4. prednisone dose at each visit [ Time Frame: 52 weeks ]
   compare the prednisone dose at each visit
5. SELENA-SLEDAI score at each visit [ Time Frame: 52 weeks ]
   compare the disease activity measured by SELENA-SLEDAI score at each visit
6. BiLAG score at each visit [ Time Frame: 52 weeks ]
   compare the disease activity measured by BILAG score at each visit
7. Adverse events [ Time Frame: 52 weeks ]
   the safety of belimumab

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Meet the 1997 revised American College of Rheumatology criteria for SLE;
• Patients with low disease activity (score≤ 6 at screening on SLEDAI); no British Isles Lupus Assessment Group (BILAG) A and no more than one B;
• A stable treatment regimen with fixed doses of prednisone (≤ 20mg/day), antimalarial, or immunosuppressive drugs (azathioprine/ mycophenolate mofetil/ methotrexate/ ciclosporin/ leflunomide/ tacrolimus) for at least 30 days.
• Sign the informed consent;

Exclusion Criteria:

• Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 2 times upper normal limits;
• Creatinine clearance rate < 60ml/min;
• Exposure to cyclophosphamide or any B cell targeted therapy (Rituximab/belimumab) within past 6 months before screening;
• History of Malignancy;
• History of herpes zoster with past 3 months before screening.

Contacts and Locations

No Contacts or Locations Provided

More Information

Publications:

Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, León MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA; BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Feb 26;377(9767):721-31. doi: 10.1016/S0140-6736(10)61354-2. Epub 2011 Feb 4.

• Responsible Party: RenJi Hospital
• ClinicalTrials.gov Identifier: NCT04515719
• Other Study ID Numbers: Btrial
• First Posted: August 17, 2020
• Last Update Posted: August 18, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by RenJi Hospital:

Belimumab; Systemic Lupus Erythematosus; Disease flare

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Belimumab; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs