Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000464965
Ethics application status
Approved
Date submitted
2/05/2011
Date registered
5/05/2011
Date last updated
10/05/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Study of Epratuzumab versus Placebo in subjects with moderate to severe general Systemic Lupus Erythematosus (SLE)
Scientific title
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 (EMBODY 1)
Secondary ID [1] 260095 0
NCT01262365 ClinicalTrials.gov
Universal Trial Number (UTN)
Trial acronym
EMBODY 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus 265771 0
Condition category
Condition code
Inflammatory and Immune System 265919 265919 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 – Epratuzumab 600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles
Arm 2 – Epratuzumab 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
Arm 3 – Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles
Intervention code [1] 264507 0
Treatment: Drugs
Comparator / control treatment
Placebo infusion - 0.04M PBS with 0.02% polysorbate 80, pH 7.4
Control group
Placebo

Outcomes
Primary outcome [1] 266680 0
The percent of subjects meeting treatment response criteria at Week 48 according to a combined response index which incorporates criteria for achievement of responder status from the BILAG, SLEDAI, physician's global assessment of disease activity, and concomitant
medication.
Timepoint [1] 266680 0
Week 48
Secondary outcome [1] 276180 0
The percent of subjects meeting treatment response criteria at Week 24 according to a combined response index which incorporates criteria for achievement of responder status from the BILAG, SLEDAI, physician's global assessment of disease activity, and concomitant
medication.
Timepoint [1] 276180 0
Week 24
Secondary outcome [2] 276181 0
The percent of subjects meeting treatment response criteria at Week 12 according to a combined response index which incorporates criteria for achievement of responder status from the BILAG, SLEDAI, physician's global assessment of disease activity, and concomitant
medication.
Timepoint [2] 276181 0
Week 12
Secondary outcome [3] 276182 0
The percent of subjects meeting treatment response criteria at Week 36 according to a combined response index which incorporates criteria for achievement of responder status from the BILAG, SLEDAI, physician's global assessment of disease activity, and concomitant
medication.
Timepoint [3] 276182 0
Week 36
Secondary outcome [4] 276183 0
Change from Baseline in daily corticosteroid dose at week 24
Timepoint [4] 276183 0
Baseline, week 24
Secondary outcome [5] 276184 0
Change from Baseline in daily corticosteroid dose at week 48
Timepoint [5] 276184 0
Baseline, week 48

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be screened during the screening period for assessment of study selection criteria and must have at least 1 BILAG level A active body/organ, or at least 2 BILAG level B active body/organ systems at Baseline (Visit 1) among the BILAG-defined mucocutaneous, musculoskeletal, or cardio respiratory body systems as determined by the central independent efficacy reader for BILAG data.
Patients qualifying for the study according to the inclusion and exclusion criteria will be randomised to treatment in a 1:1:1 ratio.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization schedule for assigning subjects to a treatment group was based on a permuted-blocks design (i.e. blocked randomization), stratified by region and baseline disease severity. The randomization schedule was created using a UCB internal software application (SAS-based) designed for creating randomization schedules, and the randomization was generated by UCB employees otherwise not involved in the conduct of the trial. An IVRS/IWRS will be used for assigning eligible subjects to a treatment regimen based on this predetermined randomization schedule .

The randomization will be stratified by the following 2 factors:
1. Region (eg, Eastern Europe, Western Europe, Middle East and India, Far East, North America, Latin America, and the Pacific); and
2. Baseline disease status:
- SLICC/ACR Damage score =0 and <2 BILAG As at Baseline
- SLICC/ACR Damage score >0 or >=2 BILAG As at Baseline (but not both)
- SLICC/ACR Damage score >0 and >=2 BILAG As at Baseline
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
26/01/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1053
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 3963 0
3145
Recruitment postcode(s) [2] 3964 0
3168
Recruitment postcode(s) [3] 3965 0
4558
Recruitment outside Australia
Country [1] 3442 0
Belgium
State/province [1] 3442 0
Country [2] 3443 0
Brazil
State/province [2] 3443 0
Rio de Janeiro
Country [3] 3444 0
Bulgaria
State/province [3] 3444 0
Country [4] 3445 0
Czech Republic
State/province [4] 3445 0
Country [5] 3446 0
France
State/province [5] 3446 0
Country [6] 3447 0
Germany
State/province [6] 3447 0
Baden-Wurttemberg
Country [7] 3448 0
Germany
State/province [7] 3448 0
Nordrhein-Westfalen
Country [8] 3449 0
Germany
State/province [8] 3449 0
Sachsen
Country [9] 3450 0
Germany
State/province [9] 3450 0
Berlin
Country [10] 3451 0
Germany
State/province [10] 3451 0
Niedersachsen
Country [11] 3452 0
Germany
State/province [11] 3452 0
Hessen
Country [12] 3453 0
India
State/province [12] 3453 0
Karnataka
Country [13] 3454 0
India
State/province [13] 3454 0
Uttar Pradesh
Country [14] 3455 0
India
State/province [14] 3455 0
Lucknow
Country [15] 3456 0
India
State/province [15] 3456 0
Andhra Pradesh
Country [16] 3457 0
Israel
State/province [16] 3457 0
Country [17] 3458 0
Italy
State/province [17] 3458 0
Country [18] 3459 0
Korea, Democratic People's Republic Of
State/province [18] 3459 0
Country [19] 3460 0
Mexico
State/province [19] 3460 0
Jalisco
Country [20] 3461 0
Romania
State/province [20] 3461 0
Country [21] 3462 0
Russian Federation
State/province [21] 3462 0
Country [22] 3463 0
Spain
State/province [22] 3463 0
Andalucia
Country [23] 3464 0
Spain
State/province [23] 3464 0
Galicia
Country [24] 3465 0
Spain
State/province [24] 3465 0
Madrid
Country [25] 3466 0
Spain
State/province [25] 3466 0
Cataluna
Country [26] 3467 0
Spain
State/province [26] 3467 0
Pais Vasco
Country [27] 3468 0
Spain
State/province [27] 3468 0
Islas Canarias
Country [28] 3469 0
Taiwan, Province Of China
State/province [28] 3469 0
Country [29] 3470 0
United Kingdom
State/province [29] 3470 0
Essex
Country [30] 3471 0
United Kingdom
State/province [30] 3471 0
South Yorkshire
Country [31] 3472 0
United Kingdom
State/province [31] 3472 0
West Yorkshire
Country [32] 3473 0
United Kingdom
State/province [32] 3473 0
East Sussex
Country [33] 3474 0
United States of America
State/province [33] 3474 0
Alabama
Country [34] 3475 0
United States of America
State/province [34] 3475 0
Arkansas
Country [35] 3476 0
United States of America
State/province [35] 3476 0
California
Country [36] 3477 0
United States of America
State/province [36] 3477 0
Colorado
Country [37] 3478 0
United States of America
State/province [37] 3478 0
Connecticut
Country [38] 3479 0
United States of America
State/province [38] 3479 0
Florida
Country [39] 3480 0
United States of America
State/province [39] 3480 0
Georgia
Country [40] 3481 0
United States of America
State/province [40] 3481 0
Illinois
Country [41] 3482 0
United States of America
State/province [41] 3482 0
Louisiana
Country [42] 3483 0
United States of America
State/province [42] 3483 0
Maryland
Country [43] 3484 0
United States of America
State/province [43] 3484 0
Michigan
Country [44] 3485 0
United States of America
State/province [44] 3485 0
New York
Country [45] 3486 0
United States of America
State/province [45] 3486 0
North Carolina
Country [46] 3487 0
United States of America
State/province [46] 3487 0
North Dakota
Country [47] 3488 0
United States of America
State/province [47] 3488 0
Ohio
Country [48] 3489 0
United States of America
State/province [48] 3489 0
Oklahoma
Country [49] 3490 0
United States of America
State/province [49] 3490 0
Pennsylvania
Country [50] 3491 0
United States of America
State/province [50] 3491 0
South Carolina
Country [51] 3492 0
United States of America
State/province [51] 3492 0
Tennessee
Country [52] 3493 0
United States of America
State/province [52] 3493 0
Texas
Country [53] 3494 0
Brazil
State/province [53] 3494 0
Pernambuco
Country [54] 3495 0
Brazil
State/province [54] 3495 0
Rio Grande Do Sul
Country [55] 3496 0
Brazil
State/province [55] 3496 0
Bahia
Country [56] 3497 0
Brazil
State/province [56] 3497 0
Sao Paulo
Country [57] 3498 0
Mexico
State/province [57] 3498 0
Sonora

Funding & Sponsors
Funding source category [1] 264998 0
Commercial sector/Industry
Name [1] 264998 0
UCB, Inc
Country [1] 264998 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
UCB, Inc
Address
1950 Lake Park Drive, Smyrna GA 30080, USA
Country
United States of America
Secondary sponsor category [1] 264089 0
None
Name [1] 264089 0
Address [1] 264089 0
Country [1] 264089 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266951 0
Schulman Associates IRB, Inc
Ethics committee address [1] 266951 0
4290 Gelndale-Milford Rd, Cincinnati, Ohio 45242
Ethics committee country [1] 266951 0
United States of America
Date submitted for ethics approval [1] 266951 0
Approval date [1] 266951 0
15/10/2010
Ethics approval number [1] 266951 0
10-5760-0
Ethics committee name [2] 266955 0
Leading Ethics Committee: Prof. Dr. J.-M. Maloteaux
Ethics committee address [2] 266955 0
Avenue Hippocrate 55-14,
Tour Harvey-Niveau 0, 1200 Bruxelles.
Ethics committee country [2] 266955 0
Belgium
Date submitted for ethics approval [2] 266955 0
Approval date [2] 266955 0
31/01/2011
Ethics approval number [2] 266955 0
OM 003
Ethics committee name [3] 266956 0
Leading Ethics Committee: CPP - Ile de France V1
Ethics committee address [3] 266956 0
10, Pavilion Jacquard
47, Bd De L'Hopital
75651 Paris Cedex 13
Ethics committee country [3] 266956 0
France
Date submitted for ethics approval [3] 266956 0
Approval date [3] 266956 0
21/01/2011
Ethics approval number [3] 266956 0
CPP no 112-10
Ethics committee name [4] 266957 0
Institute review board of Gangnam Severance Hospital
Ethics committee address [4] 266957 0
712 Eonguro Ganman-gu, Seoul, 135-720
Ethics committee country [4] 266957 0
Korea, Democratic People's Republic Of
Date submitted for ethics approval [4] 266957 0
Approval date [4] 266957 0
26/01/2011
Ethics approval number [4] 266957 0
3-2010-0237
Ethics committee name [5] 266958 0
Medical Institution's Helsinki Committee to Conduct a Clinical Trial in Human Beings
Ethics committee address [5] 266958 0
Helsinki Committee of Bnai Zion Medical Center, Bnai Zion Medical Center, 43 Golomb St.,P.O.Box 4940 Haifa 31048,
Ethics committee country [5] 266958 0
Israel
Date submitted for ethics approval [5] 266958 0
Approval date [5] 266958 0
29/12/2010
Ethics approval number [5] 266958 0
0143-10-BNZ
Ethics committee name [6] 266959 0
Shalby Hospital
Ethics committee address [6] 266959 0
Shalby Hospital, Opp. Karnavati Club, S.G. Road, Ahmedabad-380015,Gujarat,
Ethics committee country [6] 266959 0
India
Date submitted for ethics approval [6] 266959 0
Approval date [6] 266959 0
09/02/2011
Ethics approval number [6] 266959 0
NAP
Ethics committee name [7] 266960 0
Eulji University Hospital IRB
Ethics committee address [7] 266960 0
IRB office, Clinical trial center, Eulji University Hospital, 1306, Dunsan-dong, Seo-gu, Daejeon, 302-799
Ethics committee country [7] 266960 0
Korea, Democratic People's Republic Of
Date submitted for ethics approval [7] 266960 0
Approval date [7] 266960 0
09/02/2011
Ethics approval number [7] 266960 0
11-004
Ethics committee name [8] 267030 0
SCMC IRB
Ethics committee address [8] 267030 0
IRB office, Room 226, The Catholic University of Korea, Yeouido St. Mary's Hospital, 62 Yeouido-dong, Yeongdeungpo-gu, Seoul, 150-713
Ethics committee country [8] 267030 0
Korea, Democratic People's Republic Of
Date submitted for ethics approval [8] 267030 0
Approval date [8] 267030 0
28/02/2011
Ethics approval number [8] 267030 0
SIRB-00170-001

Summary
Brief summary
This is a Phase 3, multicenter, placebo-controlled, randomized, double-blind study to evaluate the efficacy, safety, tolerability, and immunogenicity of epratuzumab in subjects with moderate to severe general systemic lupus erythematosus (SLE).
The study population consists of subjects (>=18 years of age) receiving a stable dose of corticosteroids (5 to 60mg/day prednisone equivalents) for at least 5 days (±1 day) prior to Week 0 (Visit 2) and the first dose of study drug. Subjects must have a diagnosis of SLE by the American College of Rheumatology (ACR) revised criteria, such that at least 4 (not including Neurologic Disorder) of the 11 criteria are met (if positive for Neurologic Disorder criteria, a total of 5 of the 11 ACR criteria must be met). In addition, subjects must have British Isles Lupus Assessment Group (BILAG) Index (version 2004) level A disease activity in at least 1 body/organ system, or BILAG level B disease activity in at least 2 body/organ systems at Baseline among the BILAG-defined mucocutaneous, musculoskeletal, or cardiorespiratory body systems, and active moderate to severe SLE disease activity as demonstrated by a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score of at least 6.
Approximately 1053 subjects will be enrolled to randomize 780 subjects in this study. For each subject, the study will last a maximum of 54 weeks and will consist of a Screening Period (1 to 14 days), a double-blind Treatment Period consisting of four 12-week treatment cycles (48 weeks total), and a Safety Follow-Up Visit for subjects not participating in the open-label extension study, SL0012, at 13 weeks from their final dose of study drug, or a maximum of 4 weeks beyond Week 48 (ie, no later than Week 52). Eligible subjects will be randomized in a 1:1:1 ratio as follows:

Epratuzumab 600mg infusions delivered once a week (QW) for a total of 4 weeks (cumulative dose [CMD] 2400mg) over four 12-week treatment cycles (ie, Weeks 0, 1, 2, 3, 12, 13, 14, 15, 24, 25, 26, 27, 36, 37, 38, and 39)

Epratuzumab 1200mg infusions delivered every other week (QOW) for a total of 4 weeks (CMD 2400mg) over four 12-week treatment cycles (ie, Weeks 0, 2, 12, 14, 24, 26, 36, and38); and placebo (PBO) infusions delivered QOW for a total of 4 weeks over four 12-week treatment cycles (ie, Weeks 1, 3, 13, 15, 25, 27, 37, and 39)

PBO infusions delivered QW for a total of 4 weeks over four 12-week treatment cycles (ie, Weeks 0, 1, 2, 3, 12, 13, 14, 15, 24, 25, 26, 27, 36, 37, 38, and 39)

The primary objective of the study is to confirm the clinical efficacy of epratuzumab in the treatment of subjects with moderate to severe general SLE despite standard of care treatments (ie, corticosteroids, and potentially antimalarials and immunosuppressants) continued from Baseline.

The secondary objectives of the study are to assess the safety, tolerability, and immunogenicity of epratuzumab, and to assess the steroid-sparing effects of epratuzumab treatment.

The exploratory objectives of the study are to assess the pharmacokinetics (PK) of epratuzumab; the effects of epratuzumab treatment on individual components of the combined response index, fatigue associated with moderate to severe SLE, and the health-related quality of life (HRQoL) and utility benefits of epratuzumab treatment.
Trial website
www.embodyprogram.com
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32560 0
Address 32560 0
Country 32560 0
Phone 32560 0
Fax 32560 0
Email 32560 0
Contact person for public queries
Name 15807 0
Dulce Lauterbach
Address 15807 0
PAREXEL International Pty Ltd
Suite B Level 6, 15 Talavera Road North Ryde NSW 2113
Country 15807 0
Australia
Phone 15807 0
+61 2 8870 3100 (reception) +61 2 8870 3191 (direct)
Fax 15807 0
Email 15807 0
dulce.lauterbach@parexel.com
Contact person for scientific queries
Name 6735 0
Jenny Omadoye
Address 6735 0
Clinical Project Manager
UCB BioSciences GmbH
Alfred-Nobel-Str. 10
40789 Monheim
Country 6735 0
Germany
Phone 6735 0
+49 (0)2173 48 1024
Fax 6735 0
Email 6735 0
jenny.omadoye@ucb.com

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