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

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01262365
• Collaborator: (none)
• Enrollment: 793
• Locations: 141
• Arms: 3
• Duration (Months): 53
• Patients Per Site: 5.6
• 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: Epratuzumab; Drug: Epratuzumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 793 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: May 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: Epratuzumab; 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles; Drug: Placebo; Placebo infusions delivered weekly for 4 weeks 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. 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. 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. 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. 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]

   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.

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

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 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	069	Birmingham	Alabama	United States
2	063	Little Rock	Arkansas	United States
3	085	Escondido	California	United States
4	031	Los Angeles	California	United States
5	051	Los Angeles	California	United States
6	089	Los Angeles	California	United States
7	074	San Diego	California	United States
8	80	San Gabriel	California	United States
9	048	Aurora	Colorado	United States
10	037	Colorado Springs	Colorado	United States
11	039	Farmington	Connecticut	United States
12	042	Aventura	Florida	United States
13	090	Clearwater	Florida	United States
14	092	DeBary	Florida	United States
15	064	Jupiter	Florida	United States
16	082	Miami	Florida	United States
17	070	Ormond Beach	Florida	United States
18	084	Palm Harbor	Florida	United States
19	062	Tamarac	Florida	United States
20	050	Tampa	Florida	United States
21	087	Vero Beach	Florida	United States
22	044	Lawrenceville	Georgia	United States
23	052	Chicago	Illinois	United States
24	096	Indianapolis	Indiana	United States
25	060	Shreveport	Louisiana	United States
26	040	Baltimore	Maryland	United States
27	047	Saint Clair Shores	Michigan	United States
28	067	Las Cruces	New Mexico	United States
29	053	New York	New York	United States
30	077	Charlotte	North Carolina	United States
31	058	Durham	North Carolina	United States
32	061	Columbus	Ohio	United States
33	071	Middleburg Heights	Ohio	United States
34	041	Oklahoma City	Oklahoma	United States
35	076	Oklahoma City	Oklahoma	United States
36	097	Oklahoma City	Oklahoma	United States
37	032	Duncansville	Pennsylvania	United States
38	093	Philadelphia	Pennsylvania	United States
39	073	Pittsburgh	Pennsylvania	United States
40	094	Pittsburgh	Pennsylvania	United States
41	099	Charleston	South Carolina	United States
42	001	Columbia	South Carolina	United States
43	034	Simpsonville	South Carolina	United States
44	057	Memphis	Tennessee	United States
45	078	Austin	Texas	United States
46	098	Austin	Texas	United States
47	079	Dallas	Texas	United States
48	055	Houston	Texas	United States
49	036	Mesquite	Texas	United States
50	066	San Antonio	Texas	United States
51	426	Maroochydore	Queensland	Australia
52	425	Malvern	Victoria	Australia
53	429	Camperdown		Australia
54	427	Clayton		Australia
55	430	Liverpool		Australia
56	106	Brussels		Belgium
57	107	Brussels		Belgium
58	105	Leuven		Belgium
59	104	Liege		Belgium
60	455	Campinas		Brazil
61	453	Porto Alegre		Brazil
62	451	Recife		Brazil
63	450	Rio de Janeiro		Brazil
64	452	Salvador		Brazil
65	454	Sao Paulo		Brazil
66	201	Plovdiv		Bulgaria
67	200	Sofia		Bulgaria
68	202	Sofia		Bulgaria
69	203	Sofia		Bulgaria
70	204	Sofia		Bulgaria
71	205	Sofia		Bulgaria
72	218	Olomouc		Czechia
73	216	Praha 2		Czechia
74	215	Zlin		Czechia
75	226	Tallinn		Estonia
76	113	Lille		France
77	114	Nantes		France
78	112	Paris		France
79	116	Pessac		France
80	127	Berlin		Germany
81	128	Frankfurt		Germany
82	126	Freiburg		Germany
83	130	Hannover		Germany
84	129	Plochingen		Germany
85	351	Bangalore		India
86	352	Hyderabad		India
87	350	Lucknow		India
88	378	Ashkelon		Israel
89	376	Beer Sheva		Israel
90	375	Haifa		Israel
91	377	Haifa		Israel
92	381	Jerusalem		Israel
93	382	Kfar Saba		Israel
94	380	Rehovot		Israel
95	379	Tel Aviv		Israel
96	383	Tel-Hashomer		Israel
97	149	Ferrara		Italy
98	148	Padova		Italy
99	147	Torino		Italy
100	306	Busan		Korea, Republic of
101	303	Daegu		Korea, Republic of
102	309	Daegu		Korea, Republic of
103	308	Daejeon		Korea, Republic of
104	304	Incheon		Korea, Republic of
105	310	Jeonju		Korea, Republic of
106	301	Junggu		Korea, Republic of
107	307	Seoul		Korea, Republic of
108	302	Suwon		Korea, Republic of
109	155	Kaunas		Lithuania
110	156	Klaipeda		Lithuania
111	475	Guadalajara		Mexico
112	476	Guadalajara		Mexico
113	478	Guadalajara		Mexico
114	480	Mérida		Mexico
115	091	Cidra		Puerto Rico
116	086	San Juan		Puerto Rico
117	263	Brasov		Romania
118	260	Bucharest		Romania
119	262	Bucharest		Romania
120	264	Bucharest		Romania
121	261	Cluj-Napoca		Romania
122	281	Ekaterinburg		Russian Federation
123	285	Petrozavodsk		Russian Federation
124	284	Saint Petersburg		Russian Federation
125	165	La Laguna	Santa Cruz De Tenerife	Spain
126	164	Bilbao	Vizcaya	Spain
127	161	Barcelona		Spain
128	162	Madrid		Spain
129	163	Madrid		Spain
130	166	Malaga		Spain
131	177	Santander		Spain
132	160	Sevilla		Spain
133	325	Changhua		Taiwan
134	326	Chiayi City		Taiwan
135	328	Kaohsiung		Taiwan
136	329	Taichung		Taiwan
137	330	Taipei		Taiwan
138	178	Brighton		United Kingdom
139	182	Doncaster		United Kingdom
140	179	Leeds		United Kingdom
141	181	Romford		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: NCT01262365
• Other Study ID Numbers: SL0009; 2010-018563-41
• First Posted: Dec 17, 2010
• Last Update Posted: Sep 28, 2018
• Last Verified: Jun 1, 2018

• 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 May 2015.
Pre-assignment Detail	Participant Flow refers to the Randomized Set (RS).

Arm/Group Title	Placebo (RS)	Epratuzumab 1200 mg Every Other Week (RS)	Epratuzumab 600 mg Per Week (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	266	262	265
COMPLETED	176	181	171
NOT COMPLETED	90	81	94

Baseline Characteristics

Arm/Group Title	Placebo (Weekly Infusion)	Epratuzumab 1200 mg Every Other Week	Epratuzumab 600 mg Per Week	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	259	264	786
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	252 95.8%	254 98.1%	257 97.3%	763 97.1%
>=65 years	11 4.2%	5 1.9%	7 2.7%	23 2.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.4 (12.6)	42.5 (11.8)	42.3 (11.4)	42.1 (12.0)
Sex: Female, Male (Count of Participants)
Female	250 95.1%	243 93.8%	242 91.7%	735 93.5%
Male	13 4.9%	16 6.2%	22 8.3%	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. 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 study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.

Arm/Group Title	Placebo (Weekly Infusion) FAS	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Per Week (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	249	244	248
Number [percentage of participants]	34.1 13%	39.8 15.4%	37.5 14.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Weekly Infusion) FAS, Epratuzumab 1200 mg Every Other Week (FAS)
	Comments	Odds Ratio: Epratuzumab/Placebo calculated using logistic regression with factors for treatment, region, and baseline disease status.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.175
	Comments
	Method	Regression, Logistic
	Comments	p-values have been calculated using logistic regression with factors for treatment, region, and baseline disease status.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.307
	Confidence Interval	(2-Sided) 95%; 0.888 to 1.923
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Weekly Infusion) FAS, Epratuzumab 600 mg Per Week (FAS)
	Comments	Odds Ratio: Epratuzumab/Placebo calculated using logistic regression with factors for treatment, region, and baseline disease status.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.442
	Comments
	Method	Regression, Logistic
	Comments	p-values have been calculated using logistic regression with factors for treatment, region, and baseline disease status.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.164
	Confidence Interval	(2-Sided) 95%; 0.790 to 1.714
	Parameter Dispersion	Type: Value:
	Estimation Comments

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. 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 study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.

Arm/Group Title	Placebo (Weekly Infusion) FAS	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Per Week (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	249	244	248
Number [percentage of participants]	33.7 12.8%	43.0 16.6%	39.1 14.8%

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. 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 study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.

Arm/Group Title	Placebo (Weekly Infusion) FAS	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Per Week (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	249	244	248
Number [percentage of participants]	31.3 11.9%	42.2 16.3%	39.9 15.1%

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. 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 study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.

Arm/Group Title	Placebo (Weekly Infusion) FAS	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Per Week (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	249	244	248
Number [percentage of participants]	33.3 12.7%	41.8 16.1%	35.1 13.3%

5. Secondary Outcome

Title	Change From Baseline in Daily Corticosteroid Dose at Week 24
Description	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.
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 study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.

Arm/Group Title	Placebo (Weekly Infusion) FAS	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Per Week (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	249	244	248
Dose decreased by >50%	9.2 3.5%	8.2 3.2%	6.9 2.6%
Dose decreased >0% to <=50%	10.8 4.1%	16.4 6.3%	14.9 5.6%
No change in dose	52.2 19.8%	50.0 19.3%	50.8 19.2%
Dose increased or missing data	27.7 10.5%	25.4 9.8%	27.4 10.4%

6. Secondary Outcome

Title	Change From Baseline in Daily Corticosteroid Dose at Week 48
Description	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.
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 study drug, with the exception of 45 subjects who were randomized at Site 071, located in the USA, who were excluded from the FAS.

Arm/Group Title	Placebo (Weekly Infusion) FAS	Epratuzumab 1200 mg Every Other Week (FAS)	Epratuzumab 600 mg Per Week (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	249	244	248
Dose decreased by >50%	14.1 5.4%	11.9 4.6%	10.1 3.8%
Dose decreased >0% to <=50%	10.4 4%	14.3 5.5%	12.5 4.7%
No chnage in dose	38.6 14.7%	37.7 14.6%	37.9 14.4%
Dose increased or missing data	36.9 14%	36.1 13.9%	39.5 15%

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 4.4 years (starting in December 2010 and concluding in May 2015). The Safety Set (SS) will be utilized for TEAE reporting.
Adverse Event Reporting Description	The Safety Set consisted of all enrolled subjects who took at least 1 dose of study drug.
Arm/Group Title	Placebo (Weekly Infusion)		Epratuzumab 1200 mg Every Other Week		Epratuzumab 600 mg Per Week
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 Infusion)		Epratuzumab 1200 mg Every Other Week		Epratuzumab 600 mg Per Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/263 (0.4%)		2/259 (0.8%)		2/264 (0.8%)
Serious Adverse Events
	Placebo (Weekly Infusion)		Epratuzumab 1200 mg Every Other Week		Epratuzumab 600 mg Per Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/263 (18.3%)		44/259 (17%)		45/264 (17%)
Blood and lymphatic system disorders
Anaemia	0/263 (0%)	0	2/259 (0.8%)	2	2/264 (0.8%)	2
Neutropenia	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Pancytopenia	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Thrombocytopenia	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Splenomegaly	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Cardiac disorders
Cardiac failure	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Cardiac failure congestive	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Pericardial effusion	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Pericarditis lupus	1/263 (0.4%)	1	1/259 (0.4%)	1	0/264 (0%)	0
Pericarditis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Congenital, familial and genetic disorders
Arteriovenous malformation	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Cerebrovascular arteriovenous malformation	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Endocrine disorders
Hyperparathyroidism	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Eye disorders
Retinal detachment	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	0/263 (0%)	0	0/259 (0%)	0	3/264 (1.1%)	3
Colitis	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Gastrointestinal haemorrhage	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Impaired gastric emptying	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Lower gastrointestinal haemorrhage	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Mesenteric artery thrombosis	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Nausea	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Pancreatitis acute	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Vomiting	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	2
Abdominal discomfort	1/263 (0.4%)	2	0/259 (0%)	0	0/264 (0%)	0
Bezoar	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Diarrhoea	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
General disorders
Chest pain	2/263 (0.8%)	2	0/259 (0%)	0	2/264 (0.8%)	2
Inflammation	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Pyrexia	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Non-cardiac chest pain	2/263 (0.8%)	2	0/259 (0%)	0	0/264 (0%)	0
Serositis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Hepatobiliary disorders
Cholelithiasis	1/263 (0.4%)	1	2/259 (0.8%)	3	1/264 (0.4%)	1
Lupus hepatitis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Immune system disorders
Drug hypersensitivity	1/263 (0.4%)	1	1/259 (0.4%)	1	1/264 (0.4%)	1
Serum sickness	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Infections and infestations
Sepsis	0/263 (0%)	0	3/259 (1.2%)	3	3/264 (1.1%)	3
Cellulitis	0/263 (0%)	0	3/259 (1.2%)	3	2/264 (0.8%)	2
Urinary tract infection	0/263 (0%)	0	0/259 (0%)	0	4/264 (1.5%)	4
Pneumonia	4/263 (1.5%)	4	1/259 (0.4%)	1	2/264 (0.8%)	2
Abscess limb	0/263 (0%)	0	1/259 (0.4%)	1	1/264 (0.4%)	2
Pyelonephritis	0/263 (0%)	0	1/259 (0.4%)	1	1/264 (0.4%)	1
Abscess neck	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Appendicitis	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Atypical pneumonia	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Bacterial pyelonephritis	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Bronchopneumonia	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Diverticulitis	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Erysipelas	1/263 (0.4%)	1	0/259 (0%)	0	1/264 (0.4%)	1
Gastroenteritis viral	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Herpes zoster	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Herpes zoster meningitis	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Influenza	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Localised infection	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Lymphangitis	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Myringitis bullous	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Pelvic inflammatory disease	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Pyelonephritis acute	1/263 (0.4%)	1	1/259 (0.4%)	1	0/264 (0%)	0
Pyelonephritis chronic	1/263 (0.4%)	1	1/259 (0.4%)	1	0/264 (0%)	0
Pyomyositis	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Septic shock	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Urinary tract infection pseudomonal	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Bronchitis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Diarrhoea infectious	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Pneumococcal sepsis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Viral infection	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Femoral neck fracture	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Fibula fracture	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Foot fracture	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Investigations
Hepatic enzyme increased	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Weight decreased	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Haemoglobin decreased	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Hypophosphataemia	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Obesity	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Hyperglycaemia	2/263 (0.8%)	2	0/259 (0%)	0	0/264 (0%)	0
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus	3/263 (1.1%)	3	5/259 (1.9%)	5	3/264 (1.1%)	3
Costochondritis	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Haemarthrosis	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Musculoskeletal chest pain	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Osteonecrosis	0/263 (0%)	0	1/259 (0.4%)	2	0/264 (0%)	0
Osteoporotic fracture	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Back pain	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Cervical spinal stenosis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/263 (0%)	0	1/259 (0.4%)	1	1/264 (0.4%)	1
Colon adenoma	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Ovarian adenoma	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Squamous cell carcinoma of skin	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	3
Nervous system disorders
Convulsion	1/263 (0.4%)	1	1/259 (0.4%)	1	1/264 (0.4%)	1
Syncope	1/263 (0.4%)	1	1/259 (0.4%)	1	1/264 (0.4%)	1
Carotid artery thrombosis	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Ischaemic stroke	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Lupus encephalitis	1/263 (0.4%)	1	1/259 (0.4%)	1	0/264 (0%)	0
Partial seizures with secondary generalisation	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Hemiparesis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Hypoaesthesia	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Mononeuropathy multiplex	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Subarachnoid haemorrhage	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Psychiatric disorders
Delirium tremens	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Suicidal ideation	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Bipolar I disorder	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Depression	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Renal and urinary disorders
Lupus nephritis	2/263 (0.8%)	2	2/259 (0.8%)	2	1/264 (0.4%)	1
Nephrotic syndrome	1/263 (0.4%)	1	2/259 (0.8%)	4	0/264 (0%)	0
Renal failure	0/263 (0%)	0	1/259 (0.4%)	1	1/264 (0.4%)	1
Nephrolithiasis	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Proteinuria	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Renal failure acute	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Renal impairment	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Urinary retention	2/263 (0.8%)	2	0/259 (0%)	0	0/264 (0%)	0
Reproductive system and breast disorders
Breast ulceration	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Endometriosis	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Ovarian cyst ruptured	1/263 (0.4%)	1	1/259 (0.4%)	1	0/264 (0%)	0
Vaginal haemorrhage	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/263 (0%)	0	0/259 (0%)	0	2/264 (0.8%)	2
Pulmonary alveolar haemorrhage	0/263 (0%)	0	1/259 (0.4%)	1	1/264 (0.4%)	1
Pulmonary embolism	0/263 (0%)	0	2/259 (0.8%)	2	0/264 (0%)	0
Acute respiratory distress syndrome	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Asthma	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	2
Chronic obstructive pulmonary disease	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Pleural effusion	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Pneumothorax	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Respiratory failure	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Hidradenitis	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Swelling face	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Surgical and medical procedures
Abortion induced	0/263 (0%)	0	0/259 (0%)	0	1/264 (0.4%)	1
Vascular disorders
Hypertension	0/263 (0%)	0	0/259 (0%)	0	2/264 (0.8%)	2
Thrombophlebitis superficial	0/263 (0%)	0	1/259 (0.4%)	1	0/264 (0%)	0
Arteriosclerosis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Jugular vein thrombosis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Lupus vasculitis	1/263 (0.4%)	1	0/259 (0%)	0	0/264 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo (Weekly Infusion)		Epratuzumab 1200 mg Every Other Week		Epratuzumab 600 mg Per Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	144/263 (54.8%)		153/259 (59.1%)		141/264 (53.4%)
Gastrointestinal disorders
Nausea	23/263 (8.7%)	28	30/259 (11.6%)	44	38/264 (14.4%)	49
Diarrhoea	17/263 (6.5%)	19	21/259 (8.1%)	24	19/264 (7.2%)	28
General disorders
Fatigue	10/263 (3.8%)	10	17/259 (6.6%)	20	12/264 (4.5%)	17
Infections and infestations
Upper respiratory tract infection	30/263 (11.4%)	36	32/259 (12.4%)	38	32/264 (12.1%)	38
Urinary tract infection	30/263 (11.4%)	41	25/259 (9.7%)	29	27/264 (10.2%)	41
Nasopharyngitis	21/263 (8%)	26	20/259 (7.7%)	21	22/264 (8.3%)	29
Sinusitis	13/263 (4.9%)	14	24/259 (9.3%)	24	15/264 (5.7%)	17
Bronchitis	20/263 (7.6%)	23	12/259 (4.6%)	14	15/264 (5.7%)	18
Musculoskeletal and connective tissue disorders
Arthralgia	14/263 (5.3%)	21	20/259 (7.7%)	28	14/264 (5.3%)	24
Back pain	10/263 (3.8%)	14	19/259 (7.3%)	20	15/264 (5.7%)	17
Pain in extremity	11/263 (4.2%)	13	14/259 (5.4%)	18	9/264 (3.4%)	9
Nervous system disorders
Headache	29/263 (11%)	38	34/259 (13.1%)	42	38/264 (14.4%)	58
Dizziness	11/263 (4.2%)	11	9/259 (3.5%)	10	16/264 (6.1%)	18
Migraine	3/263 (1.1%)	4	16/259 (6.2%)	19	7/264 (2.7%)	8
Respiratory, thoracic and mediastinal disorders
Cough	12/263 (4.6%)	16	13/259 (5%)	14	12/264 (4.5%)	12
Skin and subcutaneous tissue disorders
Rash	5/263 (1.9%)	5	14/259 (5.4%)	16	8/264 (3%)	8
Vascular disorders
Hypertension	11/263 (4.2%)	12	20/259 (7.7%)	21	13/264 (4.9%)	14

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.