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

Sponsor

UCB Pharma (Industry)

Overall Status

Completed

CT.gov ID

NCT00624351

Collaborator

(none)

227

Enrollment

Locations

Arms

Duration (Months)

4.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Biological: Epratuzumab Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

227 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Aug 1, 2009

Actual Study Completion Date :

Aug 1, 2009

Arms and Interventions

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.	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.
Experimental: EMAB 400mg 400 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 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. Other: Placebo Phosphate-buffered Saline (PBS) infusion.
Experimental: EMAB 1200mg 1200 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 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. Other: Placebo Phosphate-buffered Saline (PBS) infusion.
Experimental: EMAB 1800mg 1800 mg Epratuzumab infusions at study weeks 0, and 2, and placebo at study weeks 1 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. Other: Placebo Phosphate-buffered Saline (PBS) infusion.

Outcome Measures

Primary Outcome Measures

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

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 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 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.
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.
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 [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
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 [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 [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country
1	Birmingham	Alabama	United States
2	Tucson	Arizona	United States
3	La Jolla	California	United States
4	Los Angeles	California	United States
5	San Leandro	California	United States
6	Denver	Colorado	United States
7	Farmington	Connecticut	United States
8	Aventura	Florida	United States
9	Tampa	Florida	United States
10	Baltimore	Maryland	United States
11	Brooklyn	New York	United States
12	Chapel Hill	North Carolina	United States
13	Charlotte	North Carolina	United States
14	Durham	North Carolina	United States
15	Wilmington	North Carolina	United States
16	Oklahoma City	Oklahoma	United States
17	Dallas	Texas	United States
18	Arlington	Virginia	United States
19	Milwaukee	Wisconsin	United States
20	Brussels		Belgium
21	Leuven		Belgium
22	Curitiba		Brazil
23	Goiania		Brazil
24	Porto Alegre		Brazil
25	Rio de Janeiro		Brazil
26	Sao Paulo		Brazil
27	Sorocaba		Brazil
28	Chai Wan		Hong Kong
29	Shatin		Hong Kong
30	Debrecen		Hungary
31	Zalaegerszeg		Hungary
32	Bangalore		India
33	Hyderabad		India
34	Ludhiana		India
35	Madurai		India
36	Manipal		India
37	Nagpur		India
38	Kaunas		Lithuania
39	Klaipeda		Lithuania
40	Vilnius		Lithuania
41	Elblag		Poland
42	Konskie		Poland
43	Lublin		Poland
44	Poznań		Poland
45	Torun		Poland
46	Barcelona		Spain
47	Santander		Spain
48	Valencia		Spain
49	Donetsk		Ukraine
50	Ivano-Frankivsk		Ukraine
51	Kiev		Ukraine
52	Lviv		Ukraine
53	Birmingham		United Kingdom