Safety and efficacy of Belimumab After B cell depletion therapy in systemic LUPUS erythematosus – BEAT LUPUS

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Immune System Diseases [C20]; Systemic Lupus Erythematosus; MedDRA version: 20.0Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

• Registration Number: EUCTR2015-005543-14-GB
• Lead Sponsor: niversity College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-11-19
• Last Update Posted: 26 November 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Age between 18 and 75 years
2. Patients with 4 or more criteria for SLE according to the American College of Rheumatology (ACR) 1997 criteria or SLICC 2012 criteria or biopsy proven lupus nephritis with one additional supportive test on at least two occasions (positive ANA, anti-dsDNA antibodies or anti-Sm antibodies)
3. History of anti-dsDNA antibodies detectable at least once in the past.
4. Patients have received the first infusion of this cycle of B cell depletion therapy (rituximab) 4-6 weeks before randomisation (week 0, see participant timeline).
5. No contraindications to the use of belimumab.
6. Ability to provide informed consent
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Severe critical” SLE flare defined as BILAG A flare in CNS system or any SLE manifestation requiring more immunosuppression than allowed within the protocol in the physician's opinion
2.Pregnancy and/or Breast Feeding patients
3.At risk of pregnancy and unwilling to use an acceptable form of birth control contraception (see section 6.3.1.4)
4.Prior use of Belimumab, Atacicept or any biologic therapy (except rituximab, but no other B cell depleting therapies)
5.Participation in any other interventional trial within the last 6 months
6.eGFR <30mls/min at screening
7.Active infections, including but not limited to:
i.Current or past infection with hepatitis B or C as defined by:
A.Hepatitis B surface antigen positive
B.Hepatitis B surface antibody positive and hepatitis B core antibody positive
C.Hepatitis C antibody positive
ii.Historically positive HIV test or test positive at screening for HIV
iii.Active TB.
8.Infection history:
i.Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria)
ii.Hospitalization for treatment of infection within 60 days of Day 0
iii.Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 0
9.Receipt of a live-attenuated vaccine within 3 months of week 0 (see participant timeline)
10.In the investigator’s opinion, patients that are at high risk for infection (including but not limited to in dwelling catheter, dysphagia with aspiration, decubitus ulcer, history of prior aspiration pneumonia or recurrent severe urinary tract infection)
11.IgG levels below 4.0 g/L, IgA level < 10 mg/dL (IgG and IgA test must be performed no more than 10 days before study drug commenced for the second inclusion/exclusion criteria assessment at week 0)
12.Primary immunodeficiency
13.History of malignant neoplasm within the last 5 years
14.History of cervical dysplasia CIN Grade III cervical high risk human papillomavirus or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS) within the past 3 years. The patient will be eligible after the condition has resolved (e.g., follow-up HPV test is negative or cervical abnormality has been effectively treated >1 year ago)
15.Severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, pulmonary, cardiac, or neurological disease or, in the investigator’s opinion, any other concomitant medical condition or significant abnormal laboratory value that places the participant at risk by participating in this study with the exception of diseases or conditions related to active SLE.
16.Comorbidities currently requiring systemic corticosteroid therapy.
17.Evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator’s judgement, pose a significant risk.
18.History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.
19.Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0
20.White blood cells (WBC) <1.5 x 109/L, Neutrophils <1 x 109/L measured up to 10 days before week 0 (study drug commenced)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified