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

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

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

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Other: Placebo; Biological: Epratuzumab

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
  • Leuven, Belgium
• Brazil
  • Curitiba, Brazil
  • Goiania, Brazil
  • Porto Alegre, Brazil
  • Rio de Janeiro, Brazil
  • Sao Paulo, Brazil
  • Sorocaba, Brazil
• Hong Kong
  • Chai Wan, Hong Kong
  • Shatin, Hong Kong
• Hungary
  • Debrecen, Hungary
  • Zalaegerszeg, Hungary
• India
  • Bangalore, India
  • Hyderabad, India
  • Ludhiana, India
  • Madurai, India
  • Manipal, India
  • Nagpur, India
• Lithuania
  • Kaunas, Lithuania
  • Klaipeda, Lithuania
  • Vilnius, Lithuania
• Poland
  • Elblag, Poland
  • Konskie, Poland
  • Lublin, Poland
  • Poznań, Poland
  • Torun, Poland
• Spain
  • Barcelona, Spain
  • Santander, Spain
  • Valencia, Spain
• Ukraine
  • Donetsk, Ukraine
  • Ivano-Frankivsk, Ukraine
  • Kiev, Ukraine
  • Lviv, Ukraine
• United Kingdom
  • Birmingham, United Kingdom
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arizona
    • Tucson, Arizona, United States
  • California
    • La Jolla, California, United States
    • Los Angeles, California, United States
    • San Leandro, California, United States
  • Colorado
    • Denver, Colorado, United States
  • Connecticut
    • Farmington, Connecticut, United States
  • Florida
    • Aventura, Florida, United States
    • Tampa, Florida, United States
  • Maryland
    • Baltimore, Maryland, United States
  • New York
    • Brooklyn, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
    • Charlotte, North Carolina, United States
    • Durham, North Carolina, United States
    • Wilmington, North Carolina, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Texas
    • Dallas, Texas, United States
  • Virginia
    • Arlington, Virginia, United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Phosphate-buffered Saline (PBS) infusions at study weeks 0, 1, 2, and 3.	Other: Placebo; Phosphate-buffered Saline (PBS) infusion.
Experimental: EMAB 600mg; 600 mg Epratuzumab infusions at study weeks 0, 1, 2, and 3.	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.
Experimental: EMAB 100mg; 100 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.	Other: Placebo; Phosphate-buffered Saline (PBS) infusion.; 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.
Experimental: EMAB 400mg; 400 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.	Other: Placebo; Phosphate-buffered Saline (PBS) infusion.; 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.
Experimental: EMAB 1200mg; 1200 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.	Other: Placebo; Phosphate-buffered Saline (PBS) infusion.; 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.
Experimental: EMAB 1800mg; 1800 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 and 3.	Other: Placebo; Phosphate-buffered Saline (PBS) infusion.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response at Week 12 according to a combined response index	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.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response at Week 4 according to a combined response index	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.	Week 4
Response at Week 8 according to a combined response index	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.	Week 8
Response at Week 4 according to a combined response index involving Short Form-36 (SF-36) response	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.	Week 4
Response at Week 8 according to a combined response index involving Short Form-36 (SF-36) response	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.	Week 8
Response at Week 12 according to a combined response index involving Short Form-36 (SF-36) response	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.	Week 12
Improvement (yes/no) in British Isles Lupus Assessment Group (BILAG) at Week 4		Baseline, Week 4
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 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 Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at Week 12		Baseline, Week 12
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
Short Form-36 (SF-36) response at 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.	Baseline, Week 2
Short Form-36 (SF-36) response at 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	Baseline, Week 4
Short Form-36 (SF-36) response at 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	Baseline, Week 8
Short Form-36 (SF-36) response at 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	Baseline, Week 12
European Quality of Life-5 Dimensions (EQ-5D) score at Week 12		Week 12
Time to first sustained British Isles Lupus Assessment Group (BILAG) response		From Baseline to Week 12
Time to enhanced British Isles Lupus Assessment Group (BILAG) response		From Baseline to Week 12
Treatment failure up 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.	From Baseline to Week 12
Cumulative steroid dose at Week 12		From Baseline to Week 12
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
Change from baseline in levels of circulating T cells at Week 12		Baseline, Week 12

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: February 15, 2008
• First Submitted That Met QC Criteria: February 15, 2008
• First Posted (Estimate): February 27, 2008

Study Record Updates

• Last Update Posted (Estimate): September 12, 2011
• Last Update Submitted That Met QC Criteria: September 2, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Lupus; Monoclonal antibody; B-Cell immunotherapy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Antineoplastic Agents; Antineoplastic Agents, Immunological; Epratuzumab
• Other Study ID Numbers: SL0007; 2007-002566-35 (EudraCT Number)