Study of Epratuzumab in Serologically-positive Systemic Lupus Erythematosus (SLE) Patients With Active Disease

Phase 2

Completed

• Conditions: Systemic Lupus Erythematosus
• Interventions: Biological: Epratuzumab; Other: Placebo

• Registration Number: NCT00624351
• Lead Sponsor: UCB Pharma

Brief Summary

The primary objective of the study is to assess the dose response and the dose frequency of epratuzumab in patients with SLE.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-02-15
• Study First Submitted QC: 2008-02-15
• Study First Posted: 2008-02-27
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Disposition First Submitted: 2010-11-22
• Disposition First Submitted QC: 2010-11-22
• Disposition First Posted: 2010-11-29
• Status Verified: 2011-07
• Last Update Submitted: 2011-09-02
• Last Update Posted: 2011-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 227

Inclusion Criteria

• Positive ANA result at visit 1
• Current diagnosis of systemic lupus erythematosus (SLE) by American College of Rheumatology revised criteria such that at least 4 of the 11 criteria are met
• Active moderate or severe SLE disease activity as demonstrated by British Isles Lupus Assessment Group (BILAG) A level disease activity in at least one body/organ system or BILAG B level disease activity in at least two body/organ systems if no BILAG A level disease is present
• If on antimalarials, dose regimen must be stable for 4 weeks prior to study entry.

Exclusion Criteria

• Patients receiving any live vaccination within 2 weeks prior to visit 1 or during the course of the study
• Active severe SLE disease activity which involves the central nervous system (CNS) (defined by BILAG neurologic A level activity) including transverse myelitis, psychosis and seizures
• Active severe SLE disease activity which involves the Renal system (defined by BILAG renal level A activity or Grade III or higher World Health Organization (WHO) nephritis) or serum creatinine >2.5mg/dL or clinically significant serum creatinine increase within the prior 4 weeks or proteinuria >3.5gm/day
• Patients with a history of anti-phospholipid antibody syndrome AND use of oral anticoagulants or anti-platelet treatment
• Patients with a history of chronic infection, recent significant infection, or any current sign of symptom that may indicate an infection

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EMAB 100mg	Epratuzumab	100 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
EMAB 600mg	Epratuzumab	600 mg Epratuzumab infusions at study weeks 0, 1, 2, and 3.
EMAB 1800mg	Epratuzumab	1800 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
EMAB 1800mg	Placebo	1800 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
EMAB 100mg	Placebo	100 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
EMAB 1200mg	Placebo	1200 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
Placebo	Placebo	Phosphate-buffered Saline (PBS) infusions at study weeks 0, 1, 2, and 3.
EMAB 400mg	Epratuzumab	400 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
EMAB 400mg	Placebo	400 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
EMAB 1200mg	Epratuzumab	1200 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.

Primary Outcome Measures

Name	Time	Method
Response at Week 12 according to a combined response index	Week 12	The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, and treatment failure status.

Secondary Outcome Measures

Name	Time	Method
Response at Week 4 according to a combined response index	Week 4	The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, and treatment failure status.
Response at Week 4 according to a combined response index involving Short Form-36 (SF-36) response	Week 4	The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, treatment failure status, and SF-36 response.
Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 4	Baseline, Week 4
Response at Week 8 according to a combined response index	Week 8	The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, and treatment failure status.
Response at Week 8 according to a combined response index involving Short Form-36 (SF-36) response	Week 8	The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, treatment failure status, and SF-36 response.
Response at Week 12 according to a combined response index involving Short Form-36 (SF-36) response	Week 12	The combined response index incorporates the Bristish Isles Lupus Assessment Group (BILAG) assessment, the Systemic Lupus Eyrthematosus Disease Activity Index (SLEDAI), a physician's global assessment of disease activity, treatment failure status, and SF-36 response.
Change from baseline in total British Isles Lupus Assessment Group (BILAG) score at Week 12	Baseline, Week 12
Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 2	Baseline, Week 2
Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 4	Baseline, Week 4
Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 8	Baseline, Week 8
Change from baseline in physician global assessment at Week 12	Baseline, Week 12
Change from baseline in patient global assessment at Week 12	Baseline, Week 12
Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 8	Baseline, Week 8
Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 12	Baseline, Week 12
Improvement in British Isles Lupus Assessment Group (BILAG) at Week 24	Baseline, Week 24
Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 12	Baseline, Week 12
Short Form-36 (SF-36) response at Week 2	Baseline, Week 2	SF-36 response is defined as no changes from baseline more negative than -0.8 in PCS or \> -2.5 changes in any of the 8 domain scores.
Short Form-36 (SF-36) response at Week 4	Baseline, Week 4	SF-36 response is defined as no changes from baseline more negative than -0.8 in PCS or \> -2.5 changes in any of the 8 domain scores
Short Form-36 (SF-36) response at Week 8	Baseline, Week 8	SF-36 response is defined as no changes from baseline more negative than -0.8 in PCS or \> -2.5 changes in any of the 8 domain scores
Short Form-36 (SF-36) response at Week 12	Baseline, Week 12	SF-36 response is defined as no changes from baseline more negative than -0.8 in PCS or \> -2.5 changes in any of the 8 domain scores
Time to first sustained British Isles Lupus Assessment Group (BILAG) response	From Baseline to Week 12
European Quality of Life-5 Dimensions (EQ-5D) score at Week 12	Week 12
Cumulative steroid dose at Week 12	From Baseline to Week 12
Change from baseline in levels of circulating T cells at Week 12	Baseline, Week 12
Time to enhanced British Isles Lupus Assessment Group (BILAG) response	From Baseline to Week 12
Treatment failure up to Week 12	From Baseline to Week 12	Treatment failure is defined as increase in (or addition of a new) immunosuppressive agent over baseline treatment levels, or any increase in corticosteroid baseline treatment level, or any IV, IA, or IM injections of corticosteroids.
Human anti-human antibodies (HAHA) levels at Week 12	Week 12
Change from baseline in levels of circulating B cells at Week 12	Baseline, Week 12