Patients with lupus erythematosus (LE) with active, therapy-resistant skin manifestations receiving Standard of Care (SOC) therapy MedDRA version: 20.0 Level: HLT Classification code 10025135 Term: Lupus erythematosus (incl subtypes) System Organ Class: 100000004859 MedDRA version: 21.1 Level: LLT Classification code 10025134 Term: Lupus erythematosus System Organ Class: 100000004859
Conditions
Interventions
Trade Name: Belimumab
Product Name: Belimumab
Product Code: AS (GSK1550188)
Pharmaceutical Form: Solution for injection in pre-filled syringe
Pharmaceutical form of the placebo: Suspension for inject
Sponsors
Rheinische Friedrich-Wilhelms-Universität Bonn
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years of age 2. Patients with a clinically and histologically confirmed diagnosis of LE-specific skin lesions 3. Patients with active skin manifestations at time of enrolment 4. Patients who meet at least two of the American College of Rheumatology (ACR) criteria for LE (= 2 criteria) (Patients with cutaneous forms of LE without systemic involvement who meet all inclusion criteria may be in-cluded) 5. Patients with positive ANA (titre = 1:80, at least once within the last 3 years (no longer applicable after amendment 3) 6. Total RCLASI skin activity score of = 6 7. Patients receiving stable standard therapy for at least 30 days prior to day 0; corticosteroids may have been added as new medication or dose ad-justed up to 30 days prior to day 0; new LE therapy, other than cortico-steroids, were not added within 60 days prior to day 0; permitted medica-tions for stable standard therapy alone or in combination included: o Systemic prednisone or its equivalent up to 40 mg/day and/or class I, II, or III; topical corticosteroids up to 2 times a day (lesional applica-tion only) o antimalarials including hydroxychloroquine, chloroquine or quinacrine o non-steroidal anti-inflammatory agents (NSAID) o immunosuppressive or immunomodulatory agents including metho-trexate, azathioprine, dapsone, leflunomide, mycophenolate (includ-ing mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (e.g., tacrolimus, cyclo-sporine), sirolimus, 6-mercaptopurine or thalidomide and/or topical calcineurin inhibitors (e.g., tacrolimus, pimecrolimus) up to 2 times a day (lesional application only) o Please note: Topical corticosteroids (class I, II, or III up to 2 times a day with lesional application only) or topical calcineurin inhibitors (such as tacrolimus or pimecrolimus, up to 2 times a day with lesional appli-cation only) as the only Standard of Care medication is exclusively permitted in localized CLE disease (in accordance with the EADV s2k guideline4). For severe and widespread skin manifestations, a purely topical therapy is not sufficient as SOC. 8. Subjects with the ability to follow study instructions and likely to attend and complete all required visits 9. Written informed consent of the subject Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: ? Subj not able to give consent ? Subj without legal capacity who is unable to understand the nature,scope, significance a consequences of this clinical trial ? Known history of hypersens to the IMP or to drugs with a similar chem structure ? Simultaneous particip in another interventional CT or particip in any CT involving admin of an IMP/biological agent within 60 d prior to CT beginning ? Subj with a physical or psychiatric condition which at investig's discretion may put the subj at risk, may confound the trial results, or may interfere with the subj's particip in this CT ? Known or persistent abuse of medication, drugs or alcohol within 365 d prior to d 0 ? Current or planned pregnancy or nursing women ? Females of childbearing potential, who are not using and not willing to use medically reliable methods of contracep for the entire study duration unless they are surgically sterilized/ hysterectomized or there are any other criteria considered sufficiently reliable by the investig in individual cases ? Pat with a history of malignant neoplasm within the last 5 y with the exception of basal cell or squamous cell carcinoma of skin treated with local resection only or carcinoma in situ of uterine cervix treated locally and with no evidence of metastatic disease for 3 y ? Pat with evidence of serious suicide risk incl any history of suicidal behavior in the last 6 mo and/or any suicidal ideation = 4 on the CSSRS ideation scale in the last 2 mo or who in the investig's judgment pose a significant suicide risk ? Pat who have required high-dose prednisone (>100 mg/day) or its equivalent within 90 d prior to d 0 ? Severe lupus kidney disease (proturia >6 g/24 h or equivalent using spot urine protein to creatinine ratio, or serum creatinine >2.5 mg/dL), active nephritis or have required hemodialysis or high-dose prednisone (>100 mg/day) within 90 d prior to d 0 ? Active central nervous system lupus, incl seizures, psychosis, organic brain syndrome,cerebrovascular accident, cerebritis or CNS vasculitis, that required therapeutic intervention within 60 days prior to day 0 ? History of a major organ transpl or hematopoietic stem cell/marrow transplant ? Previous treat with intravenous IG up to 3 mo fore enrolment ? Previous treat with belimumab or any investigational biologic agent within 1 year before enrolment or an investigational non biologic agent within 60 days or 5 pharmacokinetic half-lives (whichever is longer) prior to enrol ? Treatm with immunomodulating drugs for other reasons than LE within 60 d prior to d 0 ? Active skin disease other than LE-specific or LE-non-specific manifesta ? Pat previously hypersensitive to B-lymphocyte-targeted drug (incl rituximab) or Belimumab ? Currently on any suppressive therapy for a chronic infection (eg tuberculosis,pneumocystis, cytomegalovirus,..) ? Hospitaliz for treatm of infection within 60 d prior to Day 0. ? Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, antifungals or anti-parasitic agents) within 60 days prior to Day 0 ? Pat with a historically pos HIV test or test pos at screening for HIV ? Serologic evidence of current or past HepB infection based on positive testing for HBsAg or HBcAb. ? Positive test for HepC antibody ? Pat with a history of a prim immunodeficiency ? Pat with a significant IgG deficiency (IgG level < 400 mg/dL) ? Pat with an IgA deficiency (IgA level < 10 mg/dL) ? Have a history of an anaphyl reaction to parenteral admin of contrast agents, hum
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of belimumab for therapy-resistant LE-specific skin manifestations of LE patients under Standard of Care (SOC) therapy ;Secondary Objective: To assess whether the administration of belimumab in active, therapy-resistant skin manifestations of LE-patients under Standard of Care (SOC) therapy is associated with reduced concurrent medication. To assess whether the administration of belimumab in active, therapy-resistant skin manifestations of LE-patients under Standard of Care (SOC) therapy is associated with a reduction of inflammatory parameters in skin lesions and serum.;Primary end point(s): •Differences in relative change of the mean RCLASI activity score after 24 weeks (V8) between placebo- and treatment-arm;Timepoint(s) of evaluation of this end point: After 24 weeks (V8) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Change to baseline in the RCLASI activity score after 7, 28, 56, 84, 112, 140 and 168 days of treatment in both arms ? Change to baseline in the RCLASI skin activity score after 7, 28, 56, 84,112,140 and 168 days of treatment in both arms ? Change to baseline in the RCLASI alopecia activity score after 7, 28, 56, 84, 112, 140 and 168 days of treatment in both arms ? Change to baseline in the RCLASI mucous membrane lesions activity score after 7, 28, 56, 84, 112, 140 and 168 days of treatment in both arms ? Change to baseline in the SELENA-SLEDAI score after 56 and 168 days of treatment in both arms ? Change in consumption of concurrent medication after 7, 28, 56, 84, 112, 140 and 168 days of treatment in both arms ? Change in CSSRS scores after 7, 28, 56, 84,112,140 and 168 days of treatment in both arms ? Change to baseline in Dermatology Life Quality Index (DLQI) score and Beck Depression Inventory II (BDI-II) score after 56 and 168 days of treatment in both arms ? Change of lesional histological inflammation score (V0 vs V8) ? Change of lesional MxA expression (IFN-score; V0 vs V8) ? Change in gene expression profile (serum; V0 vs. V8) ? Occurrence of any adverse event (including changes in laboratory test parameters) ? Change to baseline in the RCLASI total activity score, skin activity, alope-cia activity, and mucous membrane lesions activity score at VOL-1, VOL-2, VOL-3, and Safety FU in both arms ? Change to baseline in the SELENA-SLEDAI score, DLQI score, CSSRS scores, and BDI-II score at VOL-1, VOL-2, and VOL-3 in both arms ? Change in consumption of concurrent medication at VOL-1, VOL-2, and VOL-3 in both arms;Timepoint(s) of evaluation of this end point: Timepoint(s) of evaluation of secondardy end point see E.5.2 | — |
Countries
Germany
Contacts
Public ContactVerena Proß
Studienzentrale Studienzentrum Bonn (SZB)
Outcome results
None listed