Study of Epratuzumab Versus Placebo in Subjects With Moderate to Severe General Systemic Lupus Erythematosus (EMBODY1)

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of the Efficacy and Safety of Four 12-week Treatment Cycles (48 Weeks Total) of Epratuzumab in Systemic Lupus Erythematosus Subjects With Moderate to Severe Disease

The primary objective of the study is to confirm the clinical efficacy of epratuzumab in the treatment of subjects with Systemic Lupus Erythematosus (SLE)

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 793
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
    • 429
  • Clayton, Australia
    • 427
  • Liverpool, Australia
    • 430
  • Queensland
    • Maroochydore, Queensland, Australia
      • 426
  • Victoria
    • Malvern, Victoria, Australia
      • 425
• Belgium
  • Brussels, Belgium
    • 106
  • Brussels, Belgium
    • 107
  • Leuven, Belgium
    • 105
  • Liege, Belgium
    • 104
• Brazil
  • Campinas, Brazil
    • 455
  • Porto Alegre, Brazil
    • 453
  • Recife, Brazil
    • 451
  • Rio de Janeiro, Brazil
    • 450
  • Salvador, Brazil
    • 452
  • Sao Paulo, Brazil
    • 454
• Bulgaria
  • Plovdiv, Bulgaria
    • 201
  • Sofia, Bulgaria
    • 200
  • Sofia, Bulgaria
    • 202
  • Sofia, Bulgaria
    • 203
  • Sofia, Bulgaria
    • 204
  • Sofia, Bulgaria
    • 205
• Czechia
  • Olomouc, Czechia
    • 218
  • Praha 2, Czechia
    • 216
  • Zlin, Czechia
    • 215
• Estonia
  • Tallinn, Estonia
    • 226
• France
  • Lille, France
    • 113
  • Nantes, France
    • 114
  • Paris, France
    • 112
  • Pessac, France
    • 116
• Germany
  • Berlin, Germany
    • 127
  • Frankfurt, Germany
    • 128
  • Freiburg, Germany
    • 126
  • Hannover, Germany
    • 130
  • Plochingen, Germany
    • 129
• India
  • Bangalore, India
    • 351
  • Hyderabad, India
    • 352
  • Lucknow, India
    • 350
• Israel
  • Ashkelon, Israel
    • 378
  • Beer Sheva, Israel
    • 376
  • Haifa, Israel
    • 375
  • Haifa, Israel
    • 377
  • Jerusalem, Israel
    • 381
  • Kfar Saba, Israel
    • 382
  • Rehovot, Israel
    • 380
  • Tel Aviv, Israel
    • 379
  • Tel-Hashomer, Israel
    • 383
• Italy
  • Ferrara, Italy
    • 149
  • Padova, Italy
    • 148
  • Torino, Italy
    • 147
• Korea, Republic of
  • Busan, Korea, Republic of
    • 306
  • Daegu, Korea, Republic of
    • 303
  • Daegu, Korea, Republic of
    • 309
  • Daejeon, Korea, Republic of
    • 308
  • Incheon, Korea, Republic of
    • 304
  • Jeonju, Korea, Republic of
    • 310
  • Junggu, Korea, Republic of
    • 301
  • Seoul, Korea, Republic of
    • 307
  • Suwon, Korea, Republic of
    • 302
• Lithuania
  • Kaunas, Lithuania
    • 155
  • Klaipeda, Lithuania
    • 156
• Mexico
  • Guadalajara, Mexico
    • 475
  • Guadalajara, Mexico
    • 476
  • Guadalajara, Mexico
    • 478
  • Mérida, Mexico
    • 480
• Puerto Rico
  • Cidra, Puerto Rico
    • 091
  • San Juan, Puerto Rico
    • 086
• Romania
  • Brasov, Romania
    • 263
  • Bucharest, Romania
    • 260
  • Bucharest, Romania
    • 262
  • Bucharest, Romania
    • 264
  • Cluj-Napoca, Romania
    • 261
• Russian Federation
  • Ekaterinburg, Russian Federation
    • 281
  • Petrozavodsk, Russian Federation
    • 285
  • Saint Petersburg, Russian Federation
    • 284
• Spain
  • Barcelona, Spain
    • 161
  • Madrid, Spain
    • 162
  • Madrid, Spain
    • 163
  • Malaga, Spain
    • 166
  • Santander, Spain
    • 177
  • Sevilla, Spain
    • 160
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain
      • 165
  • Vizcaya
    • Bilbao, Vizcaya, Spain
      • 164
• Taiwan
  • Changhua, Taiwan
    • 325
  • Chiayi City, Taiwan
    • 326
  • Kaohsiung, Taiwan
    • 328
  • Taichung, Taiwan
    • 329
  • Taipei, Taiwan
    • 330
• United Kingdom
  • Brighton, United Kingdom
    • 178
  • Doncaster, United Kingdom
    • 182
  • Leeds, United Kingdom
    • 179
  • Romford, United Kingdom
    • 181
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • 069
  • Arkansas
    • Little Rock, Arkansas, United States
      • 063
  • California
    • Escondido, California, United States
      • 085
    • Los Angeles, California, United States
      • 031
    • Los Angeles, California, United States
      • 051
    • Los Angeles, California, United States
      • 089
    • San Diego, California, United States
      • 074
    • San Gabriel, California, United States
      • 80
  • Colorado
    • Aurora, Colorado, United States
      • 048
    • Colorado Springs, Colorado, United States
      • 037
  • Connecticut
    • Farmington, Connecticut, United States
      • 039
  • Florida
    • Aventura, Florida, United States
      • 042
    • Clearwater, Florida, United States
      • 090
    • DeBary, Florida, United States
      • 092
    • Jupiter, Florida, United States
      • 064
    • Miami, Florida, United States
      • 082
    • Ormond Beach, Florida, United States
      • 070
    • Palm Harbor, Florida, United States
      • 084
    • Tamarac, Florida, United States
      • 062
    • Tampa, Florida, United States
      • 050
    • Vero Beach, Florida, United States
      • 087
  • Georgia
    • Lawrenceville, Georgia, United States
      • 044
  • Illinois
    • Chicago, Illinois, United States
      • 052
  • Indiana
    • Indianapolis, Indiana, United States
      • 096
  • Louisiana
    • Shreveport, Louisiana, United States
      • 060
  • Maryland
    • Baltimore, Maryland, United States
      • 040
  • Michigan
    • Saint Clair Shores, Michigan, United States
      • 047
  • New Mexico
    • Las Cruces, New Mexico, United States
      • 067
  • New York
    • New York, New York, United States
      • 053
  • North Carolina
    • Charlotte, North Carolina, United States
      • 077
    • Durham, North Carolina, United States
      • 058
  • Ohio
    • Columbus, Ohio, United States
      • 061
    • Middleburg Heights, Ohio, United States
      • 071
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • 041
    • Oklahoma City, Oklahoma, United States
      • 076
    • Oklahoma City, Oklahoma, United States
      • 097
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
      • 032
    • Philadelphia, Pennsylvania, United States
      • 093
    • Pittsburgh, Pennsylvania, United States
      • 073
    • Pittsburgh, Pennsylvania, United States
      • 094
  • South Carolina
    • Charleston, South Carolina, United States
      • 099
    • Columbia, South Carolina, United States
      • 001
    • Simpsonville, South Carolina, United States
      • 034
  • Tennessee
    • Memphis, Tennessee, United States
      • 057
  • Texas
    • Austin, Texas, United States
      • 078
    • Austin, Texas, United States
      • 098
    • Dallas, Texas, United States
      • 079
    • Houston, Texas, United States
      • 055
    • Mesquite, Texas, United States
      • 036
    • San Antonio, Texas, United States
      • 066

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 antinuclear antibodies (ANA) at Screening (Visit 1)
• Current clinical diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria such that at least 4 of the 11 criteria are met
• Active moderate to severe SLE activity as demonstrated by the British Isles Lupus Assessment Group Index (BILAG)
• Active moderate to severe SLE disease as demonstrated by SLEDAI total score.
• On stable SLE treatment regimen, including mandatory corticosteroids and immunosuppressants or antimalarials

Exclusion Criteria:

• Subjects who are breastfeeding, pregnant, or plan to become pregnant
• Subjects with active, severe SLE disease activity which involves the renal system
• Subjects with active, severe, neuropsychiatric SLE, defined as any neuropsychiatric element scoring BILAG level A disease.
• Subjects with the evidence of an immunosuppressive state
• Subjects who, in the opinion of the investigator, are at a particularly high risk of significant infection
• History of malignant cancer, except the following treated cancers: cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma.
• Subjects receiving any live vaccination within the 8 weeks prior to screening (Visit 1).
• Subjects with history of infections, including but not limited to concurrent acute or chronic viral hepatitis B or C
• Subjects with substance abuse or dependence or other relevant concurrent medical condition
• Subjects with history of thromboembolic events within 1 year of screening Visit.
• Subjects with significant hematologic abnormalities
• Subject has received treatment with other anti- B cell antibodies within 12 months prior to screening (visit 1)
• Subject use of oral anticoagulant (not including) nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 weeks prior to screening (Visit 1)
• Subject has previously participated in this study or has previously received epratuzumab treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo (Weekly infusion); Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	Drug: Placebo; Placebo infusions delivered weekly for 4 weeks over four 12-week treatment cycles
EXPERIMENTAL: Epratuzumab 600 mg per week; 600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles	Drug: Epratuzumab; 600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12- week treatment cycles; Drug: Epratuzumab; 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles
EXPERIMENTAL: Epratuzumab 1200 mg every other week; 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles and placebo infusions delivered every other week for a total of 4 weeks over four 12-week treatment cycles	Drug: Placebo; Placebo infusions delivered weekly for 4 weeks over four 12-week treatment cycles; Drug: Epratuzumab; 600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12- week treatment cycles; Drug: Epratuzumab; 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percent of Subjects Meeting Treatment Response Criteria at Week 48 According to a Combined Response Index	Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes.	At Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percent of Subjects Meeting Treatment Response Criteria at Week 24 According to a Combined Response Index	Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes.	At Week 24
The Percent of Subjects Meeting Treatment Response Criteria at Week 12 According to a Combined Response Index	Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes.	At Week 12
The Percent of Subjects Meeting Treatment Response Criteria at Week 36 According to a Combined Response Index	Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set. The combined response index incorporated criteria for achievement of responder status from the: British Isles Lupus Assessment Group Index (BILAG-2004)- improvement from study entry or no worsening in other organ systems, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; Version 2000, also known as SLEDAI-2K) - no worsening compared to study entry, physician's global assessment of disease activity(PGA)- no worsening compared to study entry, and concomitant medications- no changes.	At Week 36
Change From Baseline in Daily Corticosteroid Dose at Week 24	Subjects with a missing corticosteroid dose at any visit for any reason are counted in the Dose Increased or Missing Data category for that visit.	At Week 24
Change From Baseline in Daily Corticosteroid Dose at Week 48	Subjects with a missing corticosteroid dose at any visit for any reason are counted in the Dose Increased or Missing Data category for that visit.	At Week 48

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

General Publications

• Gottenberg JE, Dorner T, Bootsma H, Devauchelle-Pensec V, Bowman SJ, Mariette X, Bartz H, Oortgiesen M, Shock A, Koetse W, Galateanu C, Bongardt S, Wegener WA, Goldenberg DM, Meno-Tetang G, Kosutic G, Gordon C. Efficacy of Epratuzumab, an Anti-CD22 Monoclonal IgG Antibody, in Systemic Lupus Erythematosus Patients With Associated Sjogren's Syndrome: Post Hoc Analyses From the EMBODY Trials. Arthritis Rheumatol. 2018 May;70(5):763-773. doi: 10.1002/art.40425. Epub 2018 Apr 12.
• Clowse ME, Wallace DJ, Furie RA, Petri MA, Pike MC, Leszczynski P, Neuwelt CM, Hobbs K, Keiserman M, Duca L, Kalunian KC, Galateanu C, Bongardt S, Stach C, Beaudot C, Kilgallen B, Gordon C; EMBODY Investigator Group. Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials. Arthritis Rheumatol. 2017 Feb;69(2):362-375. doi: 10.1002/art.39856.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: December 14, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (ESTIMATE): December 17, 2010

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2018
• Last Update Submitted That Met QC Criteria: August 31, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Lupus; Monoclonal antibody; Epratuzumab; 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: SL0009; 2010-018563-41 (EUDRACT_NUMBER)