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

• ClinicalTrials.gov Identifier: NCT00624351
• Recruitment Status: Completed
• First Posted: February 27, 2008
• Last Update Posted: September 12, 2011
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

Tracking Information

• First Submitted Date: February 15, 2008
• First Posted Date: February 27, 2008
• Last Update Posted Date: September 12, 2011
• Study Start Date: January 2008
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2011)

Response at Week 12 according to a combined response index [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: February 15, 2008): Efficacy as measured by the responder rate according to a combined response index evaluated at week 12 (visit 10) incorporating BILAG assessment, SLEDAI, a physician's global assessment and treatment failure status. [ Time Frame: Week 12 ]

Current Secondary Outcome Measures (submitted: June 30, 2011)

• Response at Week 4 according to a combined response index [ Time Frame: 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 8 according to a combined response index [ Time Frame: 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 4 according to a combined response index involving Short Form-36 (SF-36) response [ Time Frame: 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.
• Response at Week 8 according to a combined response index involving Short Form-36 (SF-36) response [ Time Frame: 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 [ Time Frame: 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.
• Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 4 [ Time Frame: Baseline, Week 4 ]
• Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 8 [ Time Frame: Baseline, Week 8 ]
• Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Improvement in British Isles Lupus Assessment Group (BILAG) at Week 24 [ Time Frame: Baseline, Week 24 ]
• Change from baseline in total British Isles Lupus Assessment Group (BILAG) score at Week 12 [ Time Frame: Baseline, Week 12 ]
• Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 2 [ Time Frame: Baseline, Week 2 ]
• Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 4 [ Time Frame: Baseline, Week 4 ]
• Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 8 [ Time Frame: Baseline, Week 8 ]
• Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Change from baseline in physician global assessment at Week 12 [ Time Frame: Baseline, Week 12 ]
• Change from baseline in patient global assessment at Week 12 [ Time Frame: Baseline, Week 12 ]
• Short Form-36 (SF-36) response at Week 2 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
• European Quality of Life-5 Dimensions (EQ-5D) score at Week 12 [ Time Frame: Week 12 ]
• Time to first sustained British Isles Lupus Assessment Group (BILAG) response [ Time Frame: From Baseline to Week 12 ]
• Time to enhanced British Isles Lupus Assessment Group (BILAG) response [ Time Frame: From Baseline to Week 12 ]
• Treatment failure up to Week 12 [ Time Frame: 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.
• Cumulative steroid dose at Week 12 [ Time Frame: From Baseline to Week 12 ]
• Human anti-human antibodies (HAHA) levels at Week 12 [ Time Frame: Week 12 ]
• Change from baseline in levels of circulating B cells at Week 12 [ Time Frame: Baseline, Week 12 ]
• Change from baseline in levels of circulating T cells at Week 12 [ Time Frame: Baseline, Week 12 ]

Original Secondary Outcome Measures (submitted: February 15, 2008)

• The combined response index analysis described for the primary endpoint. [ Time Frame: Weeks 4 and 8 ]
• The combined response index including an additional criteria involving the SF-36 response. [ Time Frame: Weeks 4, 8 and 12 ]
• Number and percent of patients with BILAG improvement. [ Time Frame: Weeks 4, 8, 12, and 24 ]
• Change from baseline in total BILAG score. [ Time Frame: Week 12 ]
• Change from baseline in SLEDAI. [ Time Frame: Weeks 2, 4, 8 and 12 ]
• Change from baseline in physician and patient global assessments. [ Time Frame: Week 12 ]
• Percentage of patients achieving SF-36 response. [ Time Frame: At various study weeks 2 - 12 ]
• EQ-5D results at weeks 12. [ Time Frame: Week 12 ]
• Time to first sustained BILAG response [ Time Frame: Various including study weeks 6, 8 and 12 ]
• Time to enhanced BILAG response. [ Time Frame: Various including study weeks 6, 8 and 12 ]
• Proportion of patients meeting treatment failure. [ Time Frame: Various including study weeks 6, 8 and 12 ]
• Endpoints relating to use of steroids over treatment period. [ Time Frame: Various including study weeks 6, 8 and 12 ]
• Safety outcome measures include adverse events (including infusion reactions), vital signs and clinical safety laboratory assessments. [ Time Frame: Various including study weeks 6, 8 and 12 ]
• Immunogenicity as measured by human anti-human antibodies (HAHA) [ Time Frame: Various including study weeks 6, 8 and 12 ]
• Assessment of changes from baseline in levels of circulating B and T cells [ Time Frame: Various including study weeks 6, 8 and 12 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Epratuzumab in Serologically-positive Systemic Lupus Erythematosus (SLE) Patients With Active Disease
• Official Title: A Phase IIb Randomized, Double-blind, Placebo-controlled, Dose and Dose Regimen-ranging Study of the Safety and Efficacy of Epratuzumab in Serologically-positive Systemic Lupus Erythematosus (SLE) Patients With Active Disease
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Biological: Epratuzumab
  Epratuzumab at a concentration of 10 mg/mL prepared in 17.5 ml vials for slow intravenous infusion using only Phosphate buffered Saline (PBS) as a vehicle/buffer for the infusion procedure.
• Other: Placebo
  Phosphate-buffered Saline (PBS) infusion.

Study Arms

• Placebo Comparator: Placebo
  Phosphate-buffered Saline (PBS) infusions at study weeks 0, 1, 2, and 3.
  Intervention: Other: Placebo
• Experimental: EMAB 600mg
  600 mg Epratuzumab infusions at study weeks 0, 1, 2, and 3.
  Intervention: Biological: Epratuzumab
• Experimental: EMAB 100mg
  100 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
  Interventions:

  • Biological: Epratuzumab
  • Other: Placebo
• Experimental: EMAB 400mg
  400 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
  Interventions:

  • Biological: Epratuzumab
  • Other: Placebo
• Experimental: EMAB 1200mg
  1200 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
  Interventions:

  • Biological: Epratuzumab
  • Other: Placebo
• Experimental: EMAB 1800mg
  1800 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.
  Interventions:

  • Biological: Epratuzumab
  • Other: Placebo

Publications *

• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
• Wallace DJ, Kalunian K, Petri MA, Strand V, Houssiau FA, Pike M, Kilgallen B, Bongardt S, Barry A, Kelley L, Gordon C. Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis. 2014 Jan;73(1):183-90. doi: 10.1136/annrheumdis-2012-202760. Epub 2013 Jan 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 4, 2009): 227
• Original Estimated Enrollment (submitted: February 15, 2008): 210
• Actual Study Completion Date: August 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Brazil, Hong Kong, Hungary, India, Lithuania, Poland, Spain, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT00624351
• Other Study ID Numbers: SL0007; 2007-002566-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: UCB Pharma
• Original Responsible Party: Study Director, UCB
• Current Study Sponsor: UCB Pharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: UCB Clinical Trial Call Center; +1 877 822 9493 (UCB)

• PRS Account: UCB Pharma
• Verification Date: July 2011