EMBODY2: Study of Epratuzumab Versus Placebo in Subjects With Moderate to Severe General Systemic Lupus Erythematosus (SLE)

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01261793
• Collaborator: (none)
• Enrollment: 791
• Locations: 133
• Arms: 3
• Duration (Months): 54
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Drug: Placebo; Drug: Epratuzumab; Drug: Epratuzumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 791 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

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
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; 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles

Outcome Measures

Primary Outcome Measures

1. The Percent of Subjects Meeting Treatment Response Criteria at Week 48 According to a Combined Response Index [At Week 48]

   Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set (FAS). 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.

Secondary Outcome Measures

1. The Percent of Subjects Meeting Treatment Response Criteria at Week 24 According to a Combined Response Index [At Week 24]

   Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set (FAS). 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.

2. The Percent of Subjects Meeting Treatment Response Criteria at Week 12 According to a Combined Response Index [At Week 12]

   Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set (FAS). 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.

3. The Percent of Subjects Meeting Treatment Response Criteria at Week 36 According to a Combined Response Index [At Week 36]

   Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set (FAS). 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.

4. Change From Baseline in Daily Corticosteroid Dose at Week 24 [At Week 24]

   Participants were grouped into 4 categories: Dose decreased by >50%, Dose decreased >0% to ≤50%, No change in dose and Dose increased or missing data.

5. Change From Baseline in Daily Corticosteroid Dose at Week 48 [At Week 48]

   Participants were grouped into 4 categories: Dose decreased by >50%, Dose decreased >0% to ≤50%, No change in dose and Dose increased or missing data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 SLE disease activity index (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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	539	Birmingham	Alabama	United States
2	557	Little Rock	Arkansas	United States
3	515	Hemet	California	United States
4	544	Huntington Beach	California	United States
5	550	La Jolla	California	United States
6	548	Los Angeles	California	United States
7	589	San Diego	California	United States
8	531	San Leandro	California	United States
9	558	Torrance	California	United States
10	594	Westlake Village	California	United States
11	532	Denver	Colorado	United States
12	511	Bridgeport	Connecticut	United States
13	514	Brandon	Florida	United States
14	533	Fort Lauderdale	Florida	United States
15	518	Plantation	Florida	United States
16	585	Port Orange	Florida	United States
17	538	Tampa	Florida	United States
18	537	Atlanta	Georgia	United States
19	587	Decatur	Georgia	United States
20	590	Idaho Falls	Idaho	United States
21	543	Bowling Green	Kentucky	United States
22	592	Lexington	Kentucky	United States
23	576	New Orleans	Louisiana	United States
24	572	Boston	Massachusetts	United States
25	554	Ann Arbor	Michigan	United States
26	513	Lansing	Michigan	United States
27	599	Lansing	Michigan	United States
28	575	Florissant	Missouri	United States
29	549	Saint Louis	Missouri	United States
30	596	Nashua	New Hampshire	United States
31	593	Clifton	New Jersey	United States
32	568	Freehold	New Jersey	United States
33	551	Brooklyn	New York	United States
34	553	Lake Success	New York	United States
35	545	Manhasset	New York	United States
36	577	Roslyn	New York	United States
37	559	Charlotte	North Carolina	United States
38	547	Tulsa	Oklahoma	United States
39	561	Wyomissing	Pennsylvania	United States
40	535	Charleston	South Carolina	United States
41	598	Myrtle Beach	South Carolina	United States
42	571	Jackson	Tennessee	United States
43	574	Amarillo	Texas	United States
44	570	Austin	Texas	United States
45	541	Houston	Texas	United States
46	563	Houston	Texas	United States
47	562	San Antonio	Texas	United States
48	552	Chesapeake	Virginia	United States
49	534	Seattle	Washington	United States
50	954	Belo Horizonte		Brazil
51	956	Campinas		Brazil
52	955	Goiânia		Brazil
53	950	Juiz de Fora		Brazil
54	952	Rio de Janeiro		Brazil
55	506	St. John's	Newfoundland and Labrador	Canada
56	507	Mississauga	Ontario	Canada
57	508	Rimouski	Quebec	Canada
58	502	Hamilton		Canada
59	500	London		Canada
60	504	Toronto		Canada
61	517	Victoria		Canada
62	613	Caen		France
63	618	Limoges Cedex		France
64	617	Montpellier Cedex 5		France
65	614	Paris		France
66	616	Toulouse Cedex 9		France
67	628	Berlin		Germany
68	633	Berlin		Germany
69	636	Dessau		Germany
70	637	Hamburg		Germany
71	632	Herne		Germany
72	629	Kiel		Germany
73	625	Köln		Germany
74	626	Leipzig		Germany
75	634	Mainz		Germany
76	627	Münster		Germany
77	639	Wiesbaden		Germany
78	631	Zerbst		Germany
79	712	Budapest		Hungary
80	716	Budapest		Hungary
81	718	Budapest		Hungary
82	717	Debrecen		Hungary
83	711	Szeged		Hungary
84	715	Szeged		Hungary
85	713	Zalaegerszeg		Hungary
86	852	Ahmedabad		India
87	853	Bangalore		India
88	648	Milano		Italy
89	647	Pisa		Italy
90	646	Roma		Italy
91	978	Cuauhtémoc		Mexico
92	976	Mexico City		Mexico
93	982	Mexico		Mexico
94	981	Torreon		Mexico
95	743	Bydgoszcz		Poland
96	744	Czestochowa		Poland
97	752	Elblag		Poland
98	745	Katowice		Poland
99	746	Katowice		Poland
100	748	Lublin		Poland
101	750	Lublin		Poland
102	742	Poznan		Poland
103	747	Szczecin		Poland
104	751	Ustron		Poland
105	749	Warsaw		Poland
106	757	Bucharest		Romania
107	758	Bucharest		Romania
108	760	Bucharest		Romania
109	759	Constanta		Romania
110	756	Galati		Romania
111	761	Iasi		Romania
112	778	Kemerovo		Russian Federation
113	780	Kemerovo		Russian Federation
114	779	Moscow		Russian Federation
115	901	Cape Town		South Africa
116	902	Durban		South Africa
117	903	Stellenbosch		South Africa
118	661	Barcelona		Spain
119	660	Getafe		Spain
120	662	Las Palmas de Gran Canaria		Spain
121	664	Madrid		Spain
122	663	Santiago de Compostela		Spain
123	659	Vigo		Spain
124	791	Donetsk		Ukraine
125	790	Kiev		Ukraine
126	794	Kiev		Ukraine
127	797	Kiev		Ukraine
128	792	Luhansk		Ukraine
129	793	Odessa		Ukraine
130	796	Vinnytsya		Ukraine
131	677	Birmingham		United Kingdom
132	678	Christchurch		United Kingdom
133	679	London		United Kingdom

Sponsors and Collaborators

• UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT01261793
• Other Study ID Numbers: SL0010; 2010-018565-26
• First Posted: Dec 16, 2010
• Last Update Posted: Dec 4, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by UCB Pharma: Lupus; Monoclonal antibody; B-Cell immunotherapy; Epratuzumab
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic; Epratuzumab

Study Results

Participant Flow

Recruitment Details	The study started to enroll patients in December 2010 and concluded in June 2015.
Pre-assignment Detail	Participant Flow refers to the Randomized Set (RS).

Arm/Group Title	Placebo Weekly (RS)	Epratuzumab 1200 mg Every Other Week (RS)	Epratuzumab 600 mg Weekly (RS)
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	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	600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
Period Title: Overall Study
STARTED	263	262	266
COMPLETED	178	171	184
NOT COMPLETED	85	91	82

Baseline Characteristics

Arm/Group Title	Placebo Weekly (SS)	Epratuzumab 1200 mg Every Other Week (SS)	Epratuzumab 600 mg Weekly (SS)	Total Title
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	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	600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
Overall Participants	263	261	264	788
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	254 96.6%	257 98.5%	254 96.2%	765 97.1%
>=65 years	9 3.4%	4 1.5%	10 3.8%	23 2.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.1 (11.8)	40.8 (11.5)	41.2 (12.7)	41.0 (12.0)
Sex: Female, Male (Count of Participants)
Female	245 93.2%	247 94.6%	245 92.8%	737 93.5%
Male	18 6.8%	14 5.4%	19 7.2%	51 6.5%

Outcome Measures

1. Primary Outcome

Title	The Percent of Subjects Meeting Treatment Response Criteria at Week 48 According to a Combined Response Index
Description	Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set (FAS). 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.
Time Frame	At Week 48

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of the study drug.

Arm/Group Title	Placebo Weekly (FAS)	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Weekly (FAS)
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	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	600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
Measure Participants	263	261	264
Number [Percentage of responders]	33.5	34.1	35.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Weekly (FAS), Epratuzumab 1200 mg Every Other Week (FAS)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.899
	Comments	p-values for the comparison of treatment groups have been calculated using logistic regression with factors for treatment, pooled region, and baseline disease status.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.024
	Confidence Interval	(2-Sided) 95%; 0.710 to 1.477
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio: Epratuzumab/Placebo calculated using logistic regression with factors for treatment, pooled region, and baseline disease status.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Weekly (FAS), Epratuzumab 600 mg Weekly (FAS)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.716
	Comments	p-values for the comparison of treatment groups have been calculated using logistic regression with factors for treatment, pooled region, and baseline disease status.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.070
	Confidence Interval	(2-Sided) 95%; 0.743 to 1.539
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio: Epratuzumab/Placebo calculated using logistic regression with factors for treatment, pooled region, and baseline disease status.

2. Secondary Outcome

Title	The Percent of Subjects Meeting Treatment Response Criteria at Week 24 According to a Combined Response Index
Description	Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set (FAS). 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.
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of the study drug.

Arm/Group Title	Placebo Weekly (FAS)	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Weekly (FAS)
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	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	600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
Measure Participants	263	261	264
Number [Percentage of responders]	32.3	33.0	43.6

3. Secondary Outcome

Title	The Percent of Subjects Meeting Treatment Response Criteria at Week 12 According to a Combined Response Index
Description	Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set (FAS). 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.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of the study drug.

Arm/Group Title	Placebo Weekly (FAS)	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Weekly (FAS)
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	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	600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
Measure Participants	263	261	264
Number [Percentage of responders]	30.0	32.2	40.9

4. Secondary Outcome

Title	The Percent of Subjects Meeting Treatment Response Criteria at Week 36 According to a Combined Response Index
Description	Percentages are based on the number of subjects in the relevant treatment group within the Full Analysis Set (FAS). 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.
Time Frame	At Week 36

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of the study drug.

Arm/Group Title	Placebo Weekly (FAS)	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Weekly (FAS)
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	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	600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
Measure Participants	263	261	264
Number [Percentage of responders]	32.7	33.0	36.7

5. Secondary Outcome

Title	Change From Baseline in Daily Corticosteroid Dose at Week 24
Description	Participants were grouped into 4 categories: Dose decreased by >50%, Dose decreased >0% to ≤50%, No change in dose and Dose increased or missing data.
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of the study drug.

Arm/Group Title	Placebo Weekly (FAS)	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Weekly (FAS)
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	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	600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
Measure Participants	263	261	264
Dose decreased by >50%	4.6 (0)	10.0 (0)	8.7 (0)
Dose decreased >0% to ≤50%	20.9 (0)	18.0 (0)	18.2 (0)
No change in dose	48.3 (0)	46.7 (0)	52.7 (0)
Dose increased or missing data	26.2 (0)	25.3 (0)	20.5 (0)

6. Secondary Outcome

Title	Change From Baseline in Daily Corticosteroid Dose at Week 48
Description	Participants were grouped into 4 categories: Dose decreased by >50%, Dose decreased >0% to ≤50%, No change in dose and Dose increased or missing data.
Time Frame	At Week 48

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of the study drug.

Arm/Group Title	Placebo Weekly (FAS)	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Weekly (FAS)
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles	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	600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
Measure Participants	263	261	264
Dose decreased by >50%	6.5 (0) 2.5%	13.8 (0) 5.3%	14.8 (0) 5.6%
Dose decreased >0% to ≤50%	20.9 (0) 7.9%	13.4 (0) 5.1%	15.9 (0) 6%
No change in dose	35.7 (0) 13.6%	35.6 (0) 13.6%	36.7 (0) 13.9%
Dose increased or missing data	36.9 (0) 14%	37.2 (0) 14.3%	32.6 (0) 12.3%

Adverse Events

Time Frame	Treatment-emergent Adverse Events (TEAEs) were collected throughout the study (on or after first infusion of study drug and within 75 days of the last infusion), for an average of 4.5 years (starting in December 2010 and concluding in June 2015). The Safety Set will be utilized for TEAE reporting.
Adverse Event Reporting Description	The Safety Set (SS) consisted of all subjects in the Randomized Set (RS) who had received at least 1 partial dose of study drug.
Arm/Group Title	Placebo Weekly (SS)		Epratuzumab 1200 mg Every Other Week (SS)		Epratuzumab 600 mg Weekly (SS)
Arm/Group Description	Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles		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		600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12 week treatment cycles
All Cause Mortality
	Placebo Weekly (SS)		Epratuzumab 1200 mg Every Other Week (SS)		Epratuzumab 600 mg Weekly (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/263 (1.1%)		1/261 (0.4%)		0/264 (0%)
Serious Adverse Events
	Placebo Weekly (SS)		Epratuzumab 1200 mg Every Other Week (SS)		Epratuzumab 600 mg Weekly (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/263 (17.1%)		45/261 (17.2%)		50/264 (18.9%)
Blood and lymphatic system disorders
Anaemia	1/263 (0.4%)	1	2/261 (0.8%)	2	0/264 (0%)	0
Leukopenia	1/263 (0.4%)	1	0/261 (0%)	0	2/264 (0.8%)	2
Pancytopenia	0/263 (0%)	0	1/261 (0.4%)	1	1/264 (0.4%)	1
Antiphospholipid syndrome	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Thrombocytopenia	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Cardiac disorders
Angina pectoris	0/263 (0%)	0	2/261 (0.8%)	2	0/264 (0%)	0
Angina unstable	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Atrial fibrillation	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Coronary artery disease	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Palpitations	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Sinus tachycardia	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Cardiac failure congestive	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Lupus myocarditis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Mitral valve incompetence	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Myocardial infarction	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Congenital, familial and genetic disorders
Talipes	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Endocrine disorders
Goitre	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Eye disorders
Necrotising retinitis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Visual impairment	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Cataract	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Retinal degeneration	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Gastrointestinal disorders
Pancreatitis acute	0/263 (0%)	0	1/261 (0.4%)	1	1/264 (0.4%)	1
Abdominal distension	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Abdominal pain	2/263 (0.8%)	2	0/261 (0%)	0	1/264 (0.4%)	1
Abdominal pain upper	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Mechanical ileus	0/263 (0%)	0	1/261 (0.4%)	2	0/264 (0%)	0
Pancreatitis	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Reflux gastritis	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Vomiting	1/263 (0.4%)	2	0/261 (0%)	0	1/264 (0.4%)	1
Diarrhoea	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Diverticulum intestinal	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Enteritis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Gastrointestinal hypomotility	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Nausea	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
General disorders
Chest pain	2/263 (0.8%)	2	4/261 (1.5%)	5	3/264 (1.1%)	4
Asthenia	1/263 (0.4%)	1	0/261 (0%)	0	1/264 (0.4%)	1
Oedema peripheral	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Pyrexia	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Hepatobiliary disorders
Bile duct stenosis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Cholecystitis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Cholelithiasis	3/263 (1.1%)	3	0/261 (0%)	0	0/264 (0%)	0
Hepatic steatosis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Liver injury	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Immune system disorders
Anaphylactic reaction	0/263 (0%)	0	1/261 (0.4%)	1	1/264 (0.4%)	1
Drug hypersensitivity	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Infections and infestations
Pneumonia	3/263 (1.1%)	3	2/261 (0.8%)	2	4/264 (1.5%)	4
Urinary tract infection	2/263 (0.8%)	2	0/261 (0%)	0	3/264 (1.1%)	3
Sepsis	0/263 (0%)	0	2/261 (0.8%)	2	0/264 (0%)	0
Abdominal abscess	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Arthritis infective	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Cellulitis	1/263 (0.4%)	1	1/261 (0.4%)	1	0/264 (0%)	0
Cytomegalovirus chorioretinitis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Cytomegalovirus viraemia	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Dengue fever	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Dermatitis infected	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Gastroenteritis	3/263 (1.1%)	3	0/261 (0%)	0	1/264 (0.4%)	1
Gastroenteritis viral	1/263 (0.4%)	1	1/261 (0.4%)	1	0/264 (0%)	0
Herpes zoster	1/263 (0.4%)	1	0/261 (0%)	0	1/264 (0.4%)	1
Infected skin ulcer	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Infection	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Meningitis aseptic	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Pulmonary tuberculosis	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Sialoadenitis	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Skin bacterial infection	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Viral infection	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Appendicitis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Eye infection toxoplasmal	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Lobar pneumonia	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Meningitis bacterial	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Pseudomonas infection	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Pyelonephritis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Respiratory tract infection	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Injury, poisoning and procedural complications
Radius fracture	1/263 (0.4%)	1	0/261 (0%)	0	1/264 (0.4%)	1
Rib fracture	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Tendon rupture	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Ulna fracture	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Femur fracture	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Post lumbar puncture syndrome	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Investigations
Blood creatinine decreased	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Blood pressure increased	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Metabolism and nutrition disorders
Dehydration	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Diabetes mellitus	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Hypokalaemia	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus	7/263 (2.7%)	7	6/261 (2.3%)	6	6/264 (2.3%)	6
Osteonecrosis	0/263 (0%)	0	1/261 (0.4%)	1	1/264 (0.4%)	1
Arthralgia	1/263 (0.4%)	1	1/261 (0.4%)	1	0/264 (0%)	0
Compartment syndrome	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Flank pain	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Foot deformity	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Muscular weakness	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Musculoskeletal chest pain	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Musculoskeletal pain	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Musculoskeletal stiffness	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Myositis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Pain in extremity	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Periarthritis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Rhabdomyolysis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Synovitis	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Joint swelling	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Neck pain	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Patellofemoral pain syndrome	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Spinal pain	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Colon adenoma	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Papillary thyroid cancer	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Squamous cell carcinoma of skin	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Ovarian adenoma	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Nervous system disorders
Aphasia	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Cerebral infarction	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Cerebrovascular accident	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	2
Convulsion	1/263 (0.4%)	1	1/261 (0.4%)	3	0/264 (0%)	0
Dizziness	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Dysarthria	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Headache	3/263 (1.1%)	3	0/261 (0%)	0	1/264 (0.4%)	1
Lupus encephalitis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Memory impairment	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Migraine	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Myoclonus	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Nerve compression	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Syncope	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Transient ischaemic attack	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
VIIth nerve paralysis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Vasculitis cerebral	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Hemiparesis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Noninfectious myelitis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Optic neuritis	1/263 (0.4%)	2	0/261 (0%)	0	0/264 (0%)	0
Paraesthesia	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/263 (0.4%)	1	1/261 (0.4%)	1	0/264 (0%)	0
Pregnancy on contraceptive	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Psychiatric disorders
Anxiety	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Confusional state	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Depression	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	2
Generalised anxiety disorder	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Suicide attempt	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Renal and urinary disorders
Lupus nephritis	2/263 (0.8%)	2	1/261 (0.4%)	1	0/264 (0%)	0
Nephrotic syndrome	2/263 (0.8%)	2	1/261 (0.4%)	1	0/264 (0%)	0
Proteinuria	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Renal impairment	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Reproductive system and breast disorders
Cervical dysplasia	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/263 (0%)	0	0/261 (0%)	0	4/264 (1.5%)	4
Bronchiectasis	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Emphysema	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Hypoxia	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Interstitial lung disease	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	2
Lupus pleurisy	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Lupus pneumonitis	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Pleurisy	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Pulmonary alveolar haemorrhage	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Pulmonary hypertension	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Pulmonary mass	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Pneumothorax	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Purpura	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Rash	1/263 (0.4%)	1	0/261 (0%)	0	1/264 (0.4%)	1
Stevens-Johnson syndrome	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Angioedema	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Cutaneous vasculitis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Surgical and medical procedures
Abortion induced	0/263 (0%)	0	1/261 (0.4%)	1	0/264 (0%)	0
Vascular disorders
Hypertensive crisis	0/263 (0%)	0	2/261 (0.8%)	2	1/264 (0.4%)	1
Hypertension	0/263 (0%)	0	2/261 (0.8%)	2	0/264 (0%)	0
Lymphoedema	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Raynaud's phenomenon	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Temporal arteritis	0/263 (0%)	0	0/261 (0%)	0	1/264 (0.4%)	1
Deep vein thrombosis	1/263 (0.4%)	1	0/261 (0%)	0	0/264 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo Weekly (SS)		Epratuzumab 1200 mg Every Other Week (SS)		Epratuzumab 600 mg Weekly (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	151/263 (57.4%)		145/261 (55.6%)		158/264 (59.8%)
Gastrointestinal disorders
Nausea	36/263 (13.7%)	51	32/261 (12.3%)	41	25/264 (9.5%)	38
Diarrhoea	19/263 (7.2%)	24	15/261 (5.7%)	15	25/264 (9.5%)	41
Vomiting	16/263 (6.1%)	18	12/261 (4.6%)	14	16/264 (6.1%)	23
General disorders
Fatigue	14/263 (5.3%)	17	15/261 (5.7%)	31	15/264 (5.7%)	18
Pyrexia	17/263 (6.5%)	19	8/261 (3.1%)	9	13/264 (4.9%)	18
Infections and infestations
Upper respiratory tract infection	37/263 (14.1%)	46	38/261 (14.6%)	49	37/264 (14%)	47
Urinary tract infection	44/263 (16.7%)	66	37/261 (14.2%)	45	38/264 (14.4%)	54
Nasopharyngitis	21/263 (8%)	23	15/261 (5.7%)	23	24/264 (9.1%)	31
Sinusitis	19/263 (7.2%)	23	12/261 (4.6%)	17	20/264 (7.6%)	23
Bronchitis	23/263 (8.7%)	24	13/261 (5%)	13	11/264 (4.2%)	13
Musculoskeletal and connective tissue disorders
Back pain	19/263 (7.2%)	20	14/261 (5.4%)	16	14/264 (5.3%)	14
Nervous system disorders
Headache	42/263 (16%)	68	29/261 (11.1%)	39	33/264 (12.5%)	50
Dizziness	13/263 (4.9%)	20	10/261 (3.8%)	15	14/264 (5.3%)	16
Psychiatric disorders
Depression	15/263 (5.7%)	16	10/261 (3.8%)	11	9/264 (3.4%)	10
Respiratory, thoracic and mediastinal disorders
Cough	12/263 (4.6%)	12	12/261 (4.6%)	12	16/264 (6.1%)	19
Vascular disorders
Hypertension	12/263 (4.6%)	12	13/261 (5%)	15	17/264 (6.4%)	17

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.