A Phase II Study to Evaluate Safety and Efficacy of ALX-0061 in Subjects With Systemic Lupus Erythematosus

• ClinicalTrials.gov Identifier: NCT02437890
• Recruitment Status: Completed
• First Posted: May 8, 2015
• Results First Posted: February 6, 2019
• Last Update Posted: February 26, 2019
• Sponsor: Ablynx, a Sanofi company
• Information provided by (Responsible Party): Ablynx, a Sanofi company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Lupus Erythematosus, Systemic
• Interventions: Biological: ALX-0061; Biological: Placebo
• Enrollment: 312

Participant Flow

Recruitment Details	A total of 312 subjects were randomized at 91 sites located in Europe (37 sites; 155 subjects), Asia-Pacific (19 sites, 53 subjects), North America (21 sites; 52 subjects), and Latin America (14 sites, 52 subjects). Consent was obtained from the first subject on 02 July 2015; the last subject completed the final visit on 25 January 2018.
Pre-assignment Details	Of the 568 subjects screened, 256 were screen failures and 312 were randomly assigned to treatment (modified Intent-to-treat [mITT] population). All subjects received study drug and were included in the safety population. Overall, 254 subjects were included in the Per Protocol (PP) population.

Arm/Group Title	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description	Two s.c. injections with placebo every 2 weeks (q2w). *** Placebo was supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to the placebo group received 2 s.c. injections q2w: Syringe A with placebo (1 mL) q2w starting at Day 1, up to and including Week 46. Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.	ALX-0061 75 mg every 4 weeks (q4w). *** Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 75 mg q4w received 2 s.c. injections q2w: Syringe A with placebo (1 mL) q2w starting at Day 1, up to and including Week 46. Syringe B with ALX-0061 (0.5 mL) q4w at Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44, and syringe B with placebo (0.5 mL) q4w at Weeks 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46.	ALX-0061 150 mg every 4 weeks (q4w). *** Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 150 mg q4w received 2 s.c. injections q2w: Syringe A with ALX-0061 (1 mL) q4w at Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44, and syringe A with placebo (1 mL) q4w at Weeks 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46. Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.	ALX-0061 150 mg every 2 weeks (q2w). *** Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 150 mg q2w received 2 s.c. injections q2w: Syringe A with ALX-0061 (1 mL) q2w starting at Day 1, up to and including Week 46. Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.	ALX-0061 225 mg every 2 weeks (q2w). *** Vobarilizumab (ALX-0061) was supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 225 mg q2w received 2 s.c. injections q2w: Syringe A with ALX-0061 (1 mL) q2w starting at Day 1, up to and including Week 46. Syringe B with ALX-0061 (0.5 mL) q2w starting at Day 1, up to and including Week 46.
Period Title: Overall Study
Started	62	64	62	62	62
Completed	54	48	47	40	46
Not Completed	8	16	15	22	16
Reason Not Completed
Non-compliance to study drug	0	1	0	0	1
Sponsor's decision	1	1	4	0	2
Physician Decision	0	0	0	1	0
Unable to attend visit(s)	1	0	0	0	0
Lack of Efficacy	1	3	0	3	1
Adverse Event	4	9	5	11	7
Withdrawal by Subject	1	2	6	5	5
Death	0	0	0	2	0

Baseline Characteristics

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w	Total
Arm/Group Description		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every two weeks (q2w)	ALX-0061 225 mg every two weeks (q2w)	Total of all reporting groups
Overall Number of Baseline Participants		62	64	62	62	62	312
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants	312 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	62 100.0%	64 100.0%	62 100.0%	62 100.0%	62 100.0%	312 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants	312 participants
		42.3 (10.11)	42.0 (11.00)	41.8 (10.79)	39.2 (11.58)	42.0 (10.44)	41.4 (10.79)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants	312 participants
	Female	60 96.8%	61 95.3%	61 98.4%	61 98.4%	57 91.9%	300 96.2%
	Male	2 3.2%	3 4.7%	1 1.6%	1 1.6%	5 8.1%	12 3.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants	312 participants
	Hispanic or Latino	13 21.0%	12 18.8%	17 27.4%	11 17.7%	13 21.0%	66 21.2%
	Not Hispanic or Latino	49 79.0%	52 81.3%	45 72.6%	51 82.3%	49 79.0%	246 78.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants	312 participants
Argentina		4	4	3	3	4	18
Hungary		2	4	2	2	4	14
United States		10	11	10	11	10	52
Czechia		2	1	0	0	3	6
Philippines		1	3	4	3	2	13
Ukraine		5	6	7	8	7	33
Portugal		2	2	0	1	1	6
Russia		3	6	5	8	6	28
Spain		3	2	2	1	0	8
South Korea		1	1	0	2	1	5
Taiwan		3	1	1	0	2	7
Poland		4	5	3	6	5	23
Mexico		5	6	5	5	5	26
Chile		0	1	1	0	0	2
Serbia		14	11	17	11	10	63
Peru		2	0	2	1	1	6
Germany		1	0	0	0	1	2

Outcome Measures

1. Primary Outcome

Title	Number and Percentage of Subjects Who Achieved a Response at Week 24 According to the Modified British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (mBICLA) Score
Description	The primary endpoint was evaluated by determining if there was a dose-response relationship between the mBICLA response rate at Week 24 and the dose administered, using the Multiple Comparison Procedure - Modelling (MCP-Mod) methodology. The existence of several candidate parametric models was assumed and multiple comparison techniques were used to choose the model(s) most likely to represent the true underlying dose-response curve. The selected model could further be used to guide the choice of adequate doses. mBICLA responders were defined as subjects who met all of the following criteria: BILAG-2004 normal improvement: all A scores at Baseline improved to B, C or D, and all B scores improved to C or D.; No worsening in disease activity: no new BILAG-2004 A scores and ≤ 1 new increase to B.; No worsening of total mSLEDAI-2K score from Baseline.; No significant deterioration (< 10% worsening from Baseline) in PGA.; No treatment failure (including the premature
Time Frame	At Week 24 visit

Outcome Measure Data

Analysis Population Description

mITT Population - Non-response imputation (NRI)

Arm/Group Title	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:	Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed	62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
	29 46.8%	28 43.8%	24 38.7%	24 38.7%	23 37.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALX-0061 75 mg q4w, ALX-0061 150 mg q4w, ALX-0061 150 mg q2w, ALX-0061 225 mg q2w
	Comments	A multiple contrast test was used to establish evidence of a drug effect by testing for a statistically significant dose-response signal for clinical endpoint and patient population investigated in the study. Candidate dose-response models were selected amongst the following types of parametric models: linear model, Emax model, logistic model, a 1st Beta model, and a 2nd Beta model. Model tested: linear model
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	= 0.526
	Comments	Threshold for statistical significance: p = 0.05
	Method	Multiple Contrast Test
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALX-0061 75 mg q4w, ALX-0061 150 mg q4w, ALX-0061 150 mg q2w, ALX-0061 225 mg q2w
	Comments	A multiple contrast test was used to establish evidence of a drug effect by testing for a statistically significant dose-response signal for clinical endpoint and patient population investigated in the study. Candidate dose-response models were selected amongst the following types of parametric models: linear model, Emax model, logistic model, a 1st Beta model, and a 2nd Beta model. Model tested: Emax model
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	= 0.504
	Comments	Threshold for statistical significance: p = 0.05
	Method	Multiple Contrast Test
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALX-0061 75 mg q4w, ALX-0061 150 mg q4w, ALX-0061 150 mg q2w, ALX-0061 225 mg q2w
	Comments	A multiple contrast test was used to establish evidence of a drug effect by testing for a statistically significant dose-response signal for clinical endpoint and patient population investigated in the study. Candidate dose-response models were selected amongst the following types of parametric models: linear model, Emax model, logistic model, a 1st Beta model, and a 2nd Beta model. Model tested: logistic model
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	= 0.548
	Comments	Threshold for statistical significance: p = 0.05
	Method	Multiple Contrast Test
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALX-0061 75 mg q4w, ALX-0061 150 mg q4w, ALX-0061 150 mg q2w, ALX-0061 225 mg q2w
	Comments	A multiple contrast test was used to establish evidence of a drug effect by testing for a statistically significant dose-response signal for clinical endpoint and patient population investigated in the study. Candidate dose-response models were selected amongst the following types of parametric models: linear model, Emax model, logistic model, a 1st Beta model, and a 2nd Beta model. Model tested: 1st Beta model
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	= 0.985
	Comments	Threshold for statistical significance: p = 0.05
	Method	Multiple Contrast Test
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALX-0061 75 mg q4w, ALX-0061 150 mg q4w, ALX-0061 150 mg q2w, ALX-0061 225 mg q2w
	Comments	A multiple contrast test was used to establish evidence of a drug effect by testing for a statistically significant dose-response signal for clinical endpoint and patient population investigated in the study. Candidate dose-response models were selected amongst the following types of parametric models: linear model, Emax model, logistic model, a 1st Beta model, and a 2nd Beta model. Model tested: 2nd Beta model
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	= 0.524
	Comments	Threshold for statistical significance: p = 0.05
	Method	Multiple Contrast Test
	Comments	[Not Specified]

2. Secondary Outcome

Title	Number and Percentage of Subjects With mBICLA Response at Week 24 and Week 48
Description	Number and percentage of mBICLA responders at Week 24 and Week 48
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	61 participants	64 participants	58 participants	62 participants	61 participants
		28 45.9%	28 43.8%	22 37.9%	24 38.7%	22 36.1%
Week 48	Number Analyzed	59 participants	61 participants	60 participants	60 participants	60 participants
		28 47.5%	32 52.5%	22 36.7%	19 31.7%	22 36.7%

3. Secondary Outcome

Title	Number and Percentage of Subjects With Modified Systemic Lupus Erythematosus Responder Index (mSRI-4) Response at Week 24 and Week 48
Description	The composite index mSRI-4 enables quantification of decrease and increase in disease activity in a broad spectrum of manifestations thereby offering a comprehensive assessment of SLE disease status. mSRI combines advantages from 3 validated measurement tools. The mSRI-4 criteria for response are: modified SLE disease activity index 2000 (mSLEDAI-2K): ≥ 4 point reduction (covers global disease improvement),; British Isles Lupus Assessment Group 2004 (BILAG-2004): no new A domain score and no more than 1 new increase to B (covers organ-specific disease improvement),; Physician's Global Assessment (PGA) (is used as validity and safety net for items that were not addressed by the other two indices): < 10% increase from Baseline (no worsening) When all 3 criteria are met, the subject is a mSRI-4 responder at that time point. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	59 participants	63 participants	58 participants	61 participants	60 participants
		37 62.7%	39 61.9%	30 51.7%	33 54.1%	29 48.3%
Week 48	Number Analyzed	58 participants	60 participants	59 participants	58 participants	60 participants
		34 58.6%	36 60.0%	29 49.2%	26 44.8%	33 55.0%

4. Secondary Outcome

Title	Number and Percentage of Subjects With mSRI-5 Response at Week 24 and Week 48
Description	The mSRI-5 criteria for response are: mSLEDAI-2K: ≥ 5 point reduction; BILAG-2004: no new A domain score and no more than 1 new increase to B domain score; PGA: no worsening (< 10% increase from Baseline) Only subjects with Baseline mSLEDAI-2K ≥ 5 were considered for the derivation of that endpoint. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	57 participants	61 participants	54 participants	59 participants	58 participants
		17 29.8%	24 39.3%	19 35.2%	20 33.9%	16 27.6%
Week 48	Number Analyzed	56 participants	58 participants	55 participants	56 participants	58 participants
		20 35.7%	28 48.3%	18 32.7%	16 28.6%	22 37.9%

5. Secondary Outcome

Title	Number and Percentage of Subjects With mSRI-6 Response at Week 24 and Week 48
Description	The mSRI-6 criteria for response are: mSLEDAI-2K: ≥ 6 point reduction; BILAG-2004: no new A domain score and no more than 1 new increase to B domain score; PGA: no worsening (< 10% increase from Baseline) Only subjects with Baseline mSLEDAI-2K ≥ 6 were considered for the derivation of that endpoint. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	57 participants	61 participants	54 participants	59 participants	58 participants
		16 28.1%	23 37.7%	19 35.2%	19 32.2%	15 25.9%
Week 48	Number Analyzed	56 participants	58 participants	55 participants	56 participants	58 participants
		20 35.7%	28 48.3%	16 29.1%	16 28.6%	22 37.9%

6. Secondary Outcome

Title	Number and Percentage of Subjects With mSRI-7 Response at Week 24 and Week 48
Description	The mSRI-7 criteria for response are: mSLEDAI-2K: ≥ 7 point reduction; BILAG-2004: no new A domain score and no more than 1 new increase to B domain score; PGA: no worsening (< 10% increase from Baseline) Only subjects with Baseline mSLEDAI-2K ≥ 7 were considered for the derivation of that endpoint. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	46 participants	47 participants	39 participants	50 participants	43 participants
		9 19.6%	8 17.0%	8 20.5%	12 24.0%	7 16.3%
Week 48	Number Analyzed	46 participants	45 participants	40 participants	47 participants	42 participants
		12 26.1%	14 31.1%	7 17.5%	8 17.0%	9 21.4%

7. Secondary Outcome

Title	Number and Percentage of Subjects With mSRI-8 Response at Week 24 and Week 48.
Description	The mSRI-8 criteria for response are: mSLEDAI-2K: ≥ 8 point reduction; BILAG-2004: no new A domain score and no more than 1 new increase to B domain score; PGA: no worsening (< 10% increase from Baseline) Only subjects with Baseline mSLEDAI-2K ≥ 8 were considered for the derivation of that endpoint. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	45 participants	47 participants	37 participants	49 participants	42 participants
		9 20.0%	7 14.9%	8 21.6%	10 20.4%	7 16.7%
Week 48	Number Analyzed	45 participants	45 participants	38 participants	46 participants	41 participants
		11 24.4%	14 31.1%	7 18.4%	7 15.2%	8 19.5%

8. Secondary Outcome

Title	Change From Baseline in Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) Score at Week 24 and Week 48
Description	The Systemic Lupus Erythematosus Disease Activity Index 2000 is a 1-page weighted score for 24 items (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, etc). The manifestations felt to be most commonly contributing to disease activity are included and scored based on the presence (= 1 multiplied by weight) or absence (= 0) within 30 days prior to the evaluation. The total score ranges from 0-105 (= sum of individual scores), with 105 being higher disease activity. mSLEDAI-2K derives from the standard index by omitting low complement. Mean changes from baseline were derived from an ANCOVA model with treatment as factor and baseline mSLEDAI-2K Score and geographic region as covariates. A negative change from baseline reflects an improvement.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score
Week 24	Number Analyzed	53 participants	50 participants	51 participants	48 participants	51 participants
		-4.0 (0.42)	-4.6 (0.43)	-3.8 (0.43)	-4.3 (0.44)	-3.6 (0.44)
Week 48	Number Analyzed	51 participants	46 participants	47 participants	36 participants	45 participants
		-4.5 (0.40)	-5.2 (0.43)	-4.3 (0.42)	-4.9 (0.48)	-4.9 (0.44)

9. Secondary Outcome

Title	Number and Percentage of Subjects With BILAG-2004 Normal Improvement at Week 24 and Week 48
Description	Normal Improvement: all A scores at baseline improved to B/C/D, and all B scores improved to C or D. Only subjects with non-missing BILAG-2004 who had at least one A or B score at Baseline were assessed for this endpoint
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	54 participants
		31 55.4%	29 55.8%	28 50.0%	25 51.0%	24 44.4%
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		34 63.0%	34 70.8%	29 58.0%	22 56.4%	25 54.3%

10. Secondary Outcome

Title	Number and Percentage of Subjects With BILAG-2004 Enhanced Improvement at Week 24 and Week 48
Description	Enhanced improvement: all A scores at baseline improved to B/C/D, and all B scores improved to C or D and no worsening between consecutive visits from baseline up to the considered visit Only subjects with non-missing BILAG-2004 who had at least one A or B score at Baseline were assessed for this endpoint
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	54 participants
		7 12.5%	16 30.8%	11 19.6%	6 12.2%	13 24.1%
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	45 participants
		5 9.3%	10 20.8%	7 14.0%	6 15.4%	7 15.6%

11. Secondary Outcome

Title	BILAG-2004 Total Score at Baseline, Week 24 and Week 48
Description	The British Isles Lupus Assessment Group 2004 (BILAG-2004) is a comprehensive composite clinical index that has been developed based on the principle of a physician's intention to treat using a nominal consensus approach. In the index, the nine systems (not organs) considered are: constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, renal, ophthalmic and hematological. Disease activity in each of the nine systems is categorized into five levels: grades A (= severe disease activity requiring systemic high dose oral corticosteroids, i.v. pulse corticosteroids, etc.) to E (= system never involved). BILAG total score is derived by assigning the following value to each grade and summing the sores over all organ systems: A = 12, B = 8, C = 1, D/E = 0. The total score ranges from 0-108, with 108 representing high disease activity in all 9 systems requiring high doses of corticosteroids, starting/increasing immunosuppressive drugs, etc.
Time Frame	At Baseline, Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score
Baseline	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants
		17.4 (0.78)	17.9 (0.69)	15.2 (0.68)	17.4 (0.71)	17.3 (0.82)
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	54 participants
		6.8 (0.78)	5.7 (0.79)	7.0 (0.76)	7.2 (0.94)	7.4 (0.84)
Week 48	Number Analyzed	53 participants	48 participants	50 participants	39 participants	45 participants
		6.0 (0.73)	4.0 (0.72)	5.2 (0.74)	6.0 (0.92)	6.2 (0.91)

12. Secondary Outcome

Title	Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Mucocutaneous System at Week 24 and Week 48
Description	An improvement is defined as an A score at Baseline improved to B/C/D, or a B score improved to C or D. Only subjects with non-missing BILAG-2004 who had at least one A or B score at Baseline were assessed for this endpoint
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	47 participants	45 participants	43 participants	43 participants	47 participants
		25 53.2%	24 53.3%	18 41.9%	21 48.8%	25 53.2%
Week 48	Number Analyzed	45 participants	41 participants	37 participants	34 participants	40 participants
		26 57.8%	27 65.9%	18 48.6%	18 52.9%	22 55.0%

13. Secondary Outcome

Title	Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Musculoskeletal System at Week 24 and Week 48
Description	An improvement is defined as an A score at Baseline improved to B/C/D, or a B score improved to C or D. Only subjects with non-missing BILAG-2004 who had at least one A or B score at Baseline were assessed for this endpoint
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	47 participants	44 participants	43 participants	45 participants	45 participants
		41 87.2%	39 88.6%	36 83.7%	36 80.0%	33 73.3%
Week 48	Number Analyzed	45 participants	40 participants	40 participants	37 participants	38 participants
		40 88.9%	38 95.0%	35 87.5%	33 89.2%	31 81.6%

14. Secondary Outcome

Title	Number and Percentage of Subjects With Persistent Minimal or no Activity in 9 Organ Systems According to BILAG-2004 Systems Tally at Week 24 and Week 48
Description	[Not Specified]
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	54 participants
		15 26.8%	24 46.2%	19 33.9%	16 32.7%	16 29.6%
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		20 37.0%	27 56.3%	23 46.0%	16 41.0%	19 41.3%

15. Secondary Outcome

Title	Change From Baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48
Description	The physician makes a mark between 0 ("no disease") and 100 mm ("severe disease") on the visual analogue scale (VAS) to indicate disease activity (independent of the subject's self-assessment). Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline PGA score and geographic region as covariates. A negative change from baseline reflects an improvement.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score on a scale
Week 24	Number Analyzed	56 participants	52 participants	55 participants	49 participants	54 participants
		-25.2 (2.03)	-28.4 (2.09)	-26.2 (2.04)	-23.5 (2.16)	-22.7 (2.08)
Week 48	Number Analyzed	54 participants	48 participants	48 participants	39 participants	46 participants
		-28.3 (1.73)	-32.9 (1.82)	-30.2 (1.82)	-30.1 (2.00)	-30.5 (1.87)

16. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment at Week 24 and Week 48
Description	The subject makes a mark between 0 ("very good") and 100 mm ("very bad") on the VAS to indicate how the subject is doing, while considering all the ways SLE affects him/her. Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline Patient's Global Assessment and geographic region as covariates. A negative change from baseline reflects an improvement.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score on a scale
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	53 participants
		-12.4 (2.87)	-13.5 (2.96)	-14.9 (2.87)	-20.1 (3.05)	-16.0 (2.98)
Week 48	Number Analyzed	54 participants	48 participants	49 participants	39 participants	46 participants
		-15.1 (2.70)	-21.5 (2.87)	-22.1 (2.82)	-27.2 (3.12)	-25.9 (2.94)

17. Secondary Outcome

Title	Change From Baseline in Proteinuria at Week 24 and Week 48
Description	Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline proteinuria and geographic region as covariates
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: g/mol
Week 24	Number Analyzed	48 participants	44 participants	48 participants	42 participants	42 participants
		6.17 (3.730)	1.77 (3.847)	1.03 (3.735)	-3.02 (3.876)	0.16 (3.962)
Week 48	Number Analyzed	43 participants	37 participants	42 participants	30 participants	36 participants
		4.89 (5.732)	3.83 (6.152)	-1.62 (5.761)	-0.49 (6.582)	-1.21 (6.191)

18. Secondary Outcome

Title	Number of Subjects Who Were Treatment-emergent Urine Sediment Positive at Week 24 and Week 48
Description	Efficacy Laboratory Parameters (Urinalysis) - Active Urine Sediment Number of subjects who were urine sediment negative at Baseline, but positive at Week 24 and Week 48, respectively.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	54 participants
		1	0	0	0	0
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		0	0	0	0	0

19. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Week 24 and Week 48
Description	Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline serum creatinine and geographic region as covariates
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: umol/L
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	53 participants
		-1.25 (2.172)	-3.29 (2.237)	-1.50 (2.182)	-3.98 (2.309)	-0.86 (2.276)
Week 48	Number Analyzed	54 participants	47 participants	50 participants	38 participants	46 participants
		1.19 (2.016)	-1.87 (2.152)	-6.26 (2.085)	-4.04 (2.359)	-1.24 (2.199)

20. Secondary Outcome

Title	Change From Baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48
Description	Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline eGFR and geographic region as covariates
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: mL/min/1.73m2
Week 24	Number Analyzed	55 participants	52 participants	56 participants	49 participants	53 participants
		-1.63 (2.869)	4.83 (2.931)	-1.72 (2.854)	-0.90 (3.044)	-8.91 (3.014)
Week 48	Number Analyzed	53 participants	47 participants	50 participants	38 participants	46 participants
		-6.00 (3.052)	2.47 (3.231)	4.66 (3.125)	-1.47 (3.562)	-8.08 (3.326)

21. Secondary Outcome

Title	Number of and Percentage Treatment Failures From Baseline to Week 24 and Week 48
Description	Defined as non-protocol allowed increase in steroid dose, start i.v. or i.m. steroids, or start or increase of immunosuppressant
Time Frame	From Baseline to Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:	Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed	62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline to Week 24	2 3.2%	0 0.0%	4 6.5%	2 3.2%	3 4.8%
Baseline to Week 48	5 8.1%	1 1.6%	9 14.5%	6 9.7%	6 9.7%

22. Secondary Outcome

Title	Number and Percentage of Subjects Experiencing Severe Flares According to BILAG-2004 Flare Index From Baseline to Week 24 and Week 48
Description	[Not Specified]
Time Frame	From Baseline to Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:	Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed	62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline to Week 24	8 12.9%	6 9.4%	6 9.7%	7 11.3%	6 9.7%
Baseline to Week 48	8 12.9%	6 9.4%	10 16.1%	9 14.5%	9 14.5%

23. Secondary Outcome

Title	Number and Percentage of Subjects Experiencing Severe Flares According to mSLEDAI-2K Flare Index (mSFI) From Baseline to Week 24 and Week 48
Description	[Not Specified]
Time Frame	From Baseline to Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:	Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed	62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline to Week 24	1 1.6%	0 0.0%	2 3.2%	2 3.2%	1 1.6%
Baseline to Week 48	4 6.5%	0 0.0%	4 6.5%	4 6.5%	2 3.2%

24. Secondary Outcome

Title	Percent Change From Baseline in Daily Dose of Steroids at Week 24 and Week 48
Description	Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline prednisone equivalent total daily dose and geographic region as covariates
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: percentage
Week 24	Number Analyzed	48 participants	43 participants	51 participants	43 participants	48 participants
		3.87 (2.781)	-0.80 (2.922)	0.25 (2.689)	-1.40 (2.940)	-3.46 (2.831)
Week 48	Number Analyzed	46 participants	40 participants	45 participants	34 participants	40 participants
		6.93 (5.047)	-3.22 (5.397)	-1.03 (5.050)	-2.32 (5.758)	-1.73 (5.521)

25. Secondary Outcome

Title	Number and Percentage of Subjects Whose Daily Dose of Steroids Was Reduced Without Severe Flares During Weeks 40-48
Description	Number and percentage of subjects whose prednisone equivalent dose was >7.5 mg/day at baseline and reduced to ≤7.5 mg/day during Weeks 40-48 without experiencing a BILAG-2004-defined or mSFI-defined severe flare after the first prednisone equivalent dose decrease.
Time Frame	Between Week 40 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
BILAG-2004-defined Flare	Number Analyzed	34 participants	36 participants	30 participants	32 participants	36 participants
		3 8.8%	2 5.6%	5 16.7%	1 3.1%	3 8.3%
mSFI-defined Flare	Number Analyzed	34 participants	36 participants	30 participants	32 participants	36 participants
		3 8.8%	2 5.6%	4 13.3%	1 3.1%	4 11.1%

26. Secondary Outcome

Title	Number and Percentage of Subjects Who Discontinued Prednisone (or Equivalent) by Week 48 Without Experiencing a Severe Flare
Description	Number and percentage of subjects who discontinued Prednisone (or equivalent) by Week 48 without experiencing a BILAG-2004-defined or mSFI-defined severe flare
Time Frame	Up to and including Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
BILAG-2004-defined Flare	Number Analyzed	54 participants	52 participants	55 participants	54 participants	56 participants
		0 0.0%	0 0.0%	1 1.8%	1 1.9%	0 0.0%
mSFI-defined Flare	Number Analyzed	54 participants	52 participants	55 participants	54 participants	56 participants
		0 0.0%	0 0.0%	2 3.6%	1 1.9%	0 0.0%

27. Secondary Outcome

Title	Change From Baseline in Physical Component Scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48
Description	The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline SF-36 Score and geographic region as covariates. A positive change denotes an improvement.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	53 participants
		4.71 (1.241)	4.56 (1.286)	6.77 (1.242)	4.67 (1.321)	5.01 (1.292)
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		3.73 (1.414)	6.97 (1.510)	8.67 (1.460)	8.62 (1.633)	8.85 (1.535)

28. Secondary Outcome

Title	Change From Baseline in Mental Component Scores of SF-36 at Week 24 and Week 48
Description	The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline SF-36 Score and geographic region as covariates. A positive change denotes an improvement.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	53 participants
		0.08 (0.703)	-0.99 (0.724)	-0.56 (0.703)	0.45 (0.749)	-1.18 (0.732)
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		1.50 (0.716)	-0.58 (0.756)	-0.07 (0.737)	-1.07 (0.827)	-2.02 (0.777)

29. Secondary Outcome

Title	Change From Baseline in 28 Joint Count Swollenness (SJC28) Score at Week 24 and Week 48
Description	Twenty-eight joints are assessed for swollenness (a score of 1 for a joint denotes a presence of swollenness). The sum is derived to create a total score (ranging from 0 to 28; where the highest score indicate all 28 joints are swollen). Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline SJC28 Score and geographic region as covariates. A negative change denotes an improvement.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	54 participants
		-4.8 (0.31)	-5.0 (0.32)	-4.9 (0.31)	-4.8 (0.33)	-4.5 (0.32)
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		-5.0 (0.28)	-5.4 (0.30)	-4.7 (0.29)	-5.1 (0.32)	-4.5 (0.30)

30. Secondary Outcome

Title	Change From Baseline in 28 Joint Count Tenderness (TJC28) Score at Week 24 and Week 48
Description	Twenty-eight joints are assessed for tenderness (a score of 1 for a joint denotes a presence of tenderness). The sum is derived to create a total score (ranging from 0 to 28; where the highest score indicate all 28 joints are tender). Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline TJC28 Score and geographic region as covariates. A negative change denotes and improvement.
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	54 participants
		-6.8 (0.49)	-6.8 (0.50)	-6.4 (0.49)	-5.8 (0.52)	-5.5 (0.50)
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		-6.6 (0.43)	-7.4 (0.46)	-6.4 (0.45)	-6.6 (0.50)	-6.5 (0.47)

31. Secondary Outcome

Title	Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48
Description	CLASI Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and nonscarring alopecia. Evaluation of erythema and scale/hyperkeratosis is based on a table: rows represent anatomical areas and columns represent major clinical symptoms. The extent of involvement for each of the skin symptoms is documented for each anatomic area (erythema: 0=absent, 1=pink, 2=red, 3=dark red; scale: 0=absent, 1=scale, 2=verrucous/hypertrophic). Mucous membrane involvement and acute hair loss are scored based on the presence (=1) or absence (=0). Nonscarring alopecia is scored as 0=absent, 1=diffuse/non-inflammatory, 2=focal or patchy in 1 quadrant, 3=focal or patchy in >1 quadrant. The total score ranges from 0-70, with higher scores indicating more severe skin disease. Mean changes from baseline were derived from an ANCOVA model with treatment as factor and baseline CLASI Activity Score and geographic region as covariates. Negative change = improvement
Time Frame	At Week 12, Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score
Week 12	Number Analyzed	26 participants	25 participants	18 participants	21 participants	24 participants
		-2.4 (0.53)	-1.9 (0.57)	-1.4 (0.65)	-1.6 (0.63)	-1.3 (0.57)
Week 24	Number Analyzed	25 participants	21 participants	17 participants	19 participants	23 participants
		-1.1 (0.53)	-2.1 (0.60)	-1.6 (0.66)	-1.3 (0.65)	-1.8 (0.57)
Week 48	Number Analyzed	24 participants	18 participants	16 participants	14 participants	21 participants
		-1.3 (0.59)	-3.0 (0.70)	-2.5 (0.73)	-2.1 (0.80)	-3.0 (0.64)

32. Secondary Outcome

Title	Change From Baseline in CLASI Damage Score at Week 12, Week 24 and Week 48
Description	CLASI Damage is scored based on dyspigmentation and scarring. Evaluation of dyspigmentation and scarring is based on a table: rows represent anatomical areas and columns represent major clinical symptoms. The extent of involvement for each of the skin symptoms is documented for each anatomic area (dyspigmentation: 0=absent, 1=present; scarring: 0=absent, 1=scarring, 2=severely atrophic scarring or panniculitis). Subjects are also asked whether dyspigmentation due to SLE lesions usually remains visible for >12 months, which is considered permanent and results in doubling of the dyspigmentation score. Scarring alopecia is scored as follows: 0=absent, 3=1 quadrant, 4=2 quadrants, 5=3 quadrants, 6=affects the whole skull. Total score ranges from 0-56, with higher scores indicating more damaged skin. Mean changes from baseline were derived from an ANCOVA model with treatment as factor and baseline CLASI Damage Score and geographic region as covariates. Negative change = improvement.
Time Frame	At Week 12, Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: score
Week 12	Number Analyzed	11 participants	14 participants	8 participants	13 participants	13 participants
		0.1 (0.49)	0.1 (0.47)	-0.1 (0.59)	-0.3 (0.52)	-0.4 (0.52)
Week 24	Number Analyzed	11 participants	11 participants	8 participants	11 participants	12 participants
		0.4 (0.61)	-0.4 (0.61)	-0.4 (0.73)	0.3 (0.67)	-0.1 (0.66)
Week 48	Number Analyzed	11 participants	9 participants	8 participants	8 participants	11 participants
		0.0 (0.57)	-0.1 (0.60)	-0.3 (0.68)	0.4 (0.68)	-0.7 (0.63)

33. Secondary Outcome

Title	ALX-0061 Serum Concentrations at Week 24 and Week 48
Description	[Not Specified]
Time Frame	At Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title		ALX-0061 75 mg 4qw	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		64	62	62	62
Geometric Mean (Standard Deviation); Unit of Measure: µg/mL
Week 24	Number Analyzed	43 participants	53 participants	47 participants	50 participants
		0.118 (2.29)	2.05 (3.89)	18.1 (1.60)	30.7 (1.62)
Week 48	Number Analyzed	33 participants	43 participants	32 participants	42 participants
		0.155 (3.28)	2.17 (3.45)	17.9 (1.71)	36.1 (1.46)

34. Secondary Outcome

Title	Actual Values of Soluble Interleukin 6 Receptor (sIL-6R) Concentrations at Baseline, Week 24, and Week 48
Description	[Not Specified]
Time Frame	At Baseline, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: ng/mL
Baseline	Number Analyzed	62 participants	63 participants	62 participants	62 participants	60 participants
		42.22 (2.496)	37.63 (1.933)	38.10 (1.895)	42.14 (3.366)	36.92 (1.810)
Week 24	Number Analyzed	55 participants	51 participants	54 participants	49 participants	53 participants
		39.70 (1.934)	198.26 (18.856)	603.51 (31.678)	668.57 (25.568)	634.49 (23.638)
Week 48	Number Analyzed	53 participants	47 participants	50 participants	38 participants	46 participants
		39.41 (2.270)	224.66 (25.515)	610.86 (29.445)	650.73 (38.516)	659.79 (32.862)

35. Secondary Outcome

Title	Actual Values of C-reactive Protein (CRP) Concentrations at Baseline, Week 24, and Week 48
Description	[Not Specified]
Time Frame	At Baseline, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: nmol/L
Baseline	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants
		43.58 (9.527)	49.05 (12.924)	38.89 (8.394)	66.32 (17.221)	32.23 (4.957)
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	53 participants
		59.43 (11.277)	47.22 (9.607)	26.08 (9.995)	3.83 (0.668)	3.20 (0.357)
Week 48	Number Analyzed	54 participants	46 participants	50 participants	38 participants	46 participants
		30.70 (4.709)	37.65 (8.647)	23.20 (6.705)	4.41 (0.988)	4.02 (0.962)

36. Secondary Outcome

Title	Actual Values of Fibrinogen Concentrations at Baseline, Week 24, and Week 48
Description	[Not Specified]
Time Frame	At Baseline, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: g/L
Baseline	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants
		3.2 (0.09)	3.2 (0.08)	3.2 (0.09)	3.2 (0.10)	3.1 (0.09)
Week 24	Number Analyzed	55 participants	52 participants	54 participants	49 participants	51 participants
		3.3 (0.08)	3.3 (0.10)	2.3 (0.12)	1.9 (0.05)	1.9 (0.05)
Week 48	Number Analyzed	51 participants	48 participants	49 participants	36 participants	46 participants
		3.3 (0.09)	3.3 (0.12)	2.3 (0.11)	1.9 (0.06)	1.9 (0.05)

37. Secondary Outcome

Title	Actual Values of Anti-double-stranded (ds) DNA Concentrations at Baseline, Week 24, and Week 48
Description	[Not Specified]
Time Frame	at Baseline, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: IU/mL
Baseline	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants
		132.90 (54.467)	145.87 (113.907)	52.88 (17.283)	68.92 (23.226)	73.34 (25.940)
Week 24	Number Analyzed	55 participants	52 participants	55 participants	49 participants	53 participants
		81.36 (30.376)	68.27 (35.053)	46.99 (33.534)	14.98 (4.499)	23.25 (6.417)
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		81.80 (24.143)	59.48 (32.190)	74.21 (48.030)	9.13 (2.108)	15.53 (6.069)

38. Secondary Outcome

Title	Actual Values of Complement C3 Concentrations at Baseline, Week 24, and Week 48
Description	[Not Specified]
Time Frame	At Baseline, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: mg/dL
Baseline	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants
		102.3 (3.82)	100.2 (4.12)	101.9 (3.79)	105.8 (4.38)	98.6 (3.98)
Week 24	Number Analyzed	55 participants	52 participants	55 participants	47 participants	52 participants
		101.7 (4.30)	95.7 (3.81)	82.0 (3.68)	75.3 (2.90)	71.8 (2.82)
Week 48	Number Analyzed	53 participants	48 participants	50 participants	38 participants	45 participants
		95.8 (4.25)	93.2 (4.20)	79.0 (3.25)	83.2 (3.18)	72.3 (2.61)

39. Secondary Outcome

Title	Actual Values of Complement C4 Concentrations at Baseline, Week 24, and Week 48
Description	[Not Specified]
Time Frame	At Baseline, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: mg/dL
Baseline	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants
		17.3 (1.08)	17.8 (1.07)	15.9 (0.96)	18.7 (1.19)	16.3 (1.04)
Week 24	Number Analyzed	54 participants	52 participants	55 participants	47 participants	52 participants
		17.5 (1.09)	17.4 (1.10)	10.6 (0.85)	8.7 (0.40)	7.9 (0.37)
Week 48	Number Analyzed	52 participants	47 participants	48 participants	38 participants	43 participants
		16.3 (1.15)	17.3 (1.27)	10.5 (0.84)	9.8 (0.89)	8.1 (0.41)

40. Secondary Outcome

Title	Actual Values for Hemolytic Complement Component 50 (CH50) at Baseline, Week 24, and Week 48
Description	[Not Specified]
Time Frame	At Baseline, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title		Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:		Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed		62	64	62	62	62
Mean (Standard Error); Unit of Measure: unit(s)
Baseline	Number Analyzed	62 participants	64 participants	62 participants	62 participants	62 participants
		101.1 (7.46)	109.6 (8.83)	98.9 (6.95)	103.0 (7.47)	82.4 (7.09)
Week 24	Number Analyzed	56 participants	52 participants	56 participants	49 participants	53 participants
		95.8 (7.94)	107.0 (7.08)	73.6 (6.94)	56.7 (4.91)	41.1 (3.63)
Week 48	Number Analyzed	54 participants	48 participants	50 participants	39 participants	46 participants
		102.2 (8.38)	113.1 (8.63)	73.5 (8.26)	68.4 (6.95)	41.9 (3.32)

41. Secondary Outcome

Title	Number and Percentage of Subjects Who Were Treatment-emergent (TE) Anti-drug Antibody (ADA) Positive
Description	[Not Specified]
Time Frame	From first administration of ALX-0061 up to and including follow-up

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Arm/Group Description:	Two s.c. injections with placebo every 2 weeks (q2w)	ALX-0061 75 mg every 4 weeks (q4w)	ALX-0061 150 mg every 4 weeks (q4w)	ALX-0061 150 mg every 2 weeks (q2w)	ALX-0061 225 mg every 2 weeks (q2w)
Overall Number of Participants Analyzed	62	64	62	62	62
Measure Type: Count of Participants; Unit of Measure: Participants
	32 51.6%	16 25.0%	18 29.0%	31 50.0%	38 61.3%

Adverse Events

Time Frame	From time of first study drug administration until the subject's study completion/discontinuation date.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo		ALX-0061 75 mg q4w		ALX-0061 150 mg q4w		ALX-0061 150 mg q2w		ALX-0061 225 mg q2w
Arm/Group Description	Two s.c. injections with placebo every 2 weeks (q2w)		ALX-0061 75 mg every 4 weeks (q4w)		ALX-0061 150 mg every 4 weeks (q4w)		ALX-0061 150 mg every 2 weeks (q2w)		ALX-0061 225 mg every 2 weeks (q2w)
All-Cause Mortality
	Placebo		ALX-0061 75 mg q4w		ALX-0061 150 mg q4w		ALX-0061 150 mg q2w		ALX-0061 225 mg q2w
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/62 (0.00%)		0/64 (0.00%)		0/62 (0.00%)		2/62 (3.23%)		0/62 (0.00%)
Serious Adverse Events
	Placebo		ALX-0061 75 mg q4w		ALX-0061 150 mg q4w		ALX-0061 150 mg q2w		ALX-0061 225 mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/62 (11.29%)		2/64 (3.13%)		4/62 (6.45%)		5/62 (8.06%)		5/62 (8.06%)
Blood and lymphatic system disorders
Anemia of chronic disease † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Thrombotic thrombocytopenic purpura † 1	1/62 (1.61%)	1	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Cardiac disorders
Cardiopulmonary failure † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Endocrine disorders
Adrenal insufficiency † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Eye disorders
Open angle glaucoma † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0	0/62 (0.00%)	0
Gastrointestinal disorders
Gastric ulcer † 1	1/62 (1.61%)	1	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Pancreatitis chronic † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1
General disorders
Pyrexia † 1	1/62 (1.61%)	1	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Immune system disorders
Allergy to arthropod sting † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0	0/62 (0.00%)	0
Infections and infestations
Cellulitis † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0	2/62 (3.23%)	2
Pneumonia † 1	2/62 (3.23%)	2	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Sinusitis † 1	1/62 (1.61%)	1	0/64 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0	0/62 (0.00%)	0
Cytomegalovirus infection † 1	1/62 (1.61%)	1	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Erysipelas † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0	0/62 (0.00%)	0
Meningitis † 1	0/62 (0.00%)	0	1/64 (1.56%)	1	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Peritonsillar abscess † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Pulmonary tuberculoma † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Subcutaneous abscess † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0	0/62 (0.00%)	0
Tuberculous pleurisy † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Injury, poisoning and procedural complications
Ligament rupture † 1	1/62 (1.61%)	1	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Ligament sprain † 1	1/62 (1.61%)	1	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Post-traumatic pain † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0	0/62 (0.00%)	0
Toxicity to various agents † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1
Nervous system disorders
Generalized tonic-clonic seizure † 1	0/62 (0.00%)	0	1/64 (1.56%)	1	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Hypoxic-ischemic encephalopathy † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Seizure † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Psychiatric disorders
Depression † 1	1/62 (1.61%)	1	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0
Suicidal ideation † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Suicide attempt † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Respiratory failure † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1	0/62 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1
Vasculitis † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	0/62 (0.00%)	0	1/62 (1.61%)	1
1 Term from vocabulary, MedDRA (20.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		ALX-0061 75 mg q4w		ALX-0061 150 mg q4w		ALX-0061 150 mg q2w		ALX-0061 225 mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/62 (64.52%)		40/64 (62.50%)		31/62 (50.00%)		47/62 (75.81%)		44/62 (70.97%)
Blood and lymphatic system disorders
Neutropenia † 1	2/62 (3.23%)	2	3/64 (4.69%)	6	3/62 (4.84%)	3	5/62 (8.06%)	9	6/62 (9.68%)	7
Gastrointestinal disorders
Diarrhoea † 1	6/62 (9.68%)	6	1/64 (1.56%)	1	0/62 (0.00%)	0	1/62 (1.61%)	1	2/62 (3.23%)	2
Nausea † 1	4/62 (6.45%)	6	1/64 (1.56%)	1	2/62 (3.23%)	2	2/62 (3.23%)	2	0/62 (0.00%)	0
General disorders
Injection site erythema † 1	0/62 (0.00%)	0	2/64 (3.13%)	3	2/62 (3.23%)	5	5/62 (8.06%)	17	5/62 (8.06%)	11
Injection site rash † 1	0/62 (0.00%)	0	3/64 (4.69%)	3	1/62 (1.61%)	1	4/62 (6.45%)	17	3/62 (4.84%)	6
Injection site reaction † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	0/62 (0.00%)	0	4/62 (6.45%)	5	1/62 (1.61%)	5
Infections and infestations
Urinary tract infection † 1	8/62 (12.90%)	11	5/64 (7.81%)	10	7/62 (11.29%)	10	3/62 (4.84%)	5	8/62 (12.90%)	12
Upper respiratory tract infection † 1	5/62 (8.06%)	5	5/64 (7.81%)	7	5/62 (8.06%)	5	5/62 (8.06%)	8	3/62 (4.84%)	5
Nasopharyngitis † 1	6/62 (9.68%)	8	6/64 (9.38%)	7	5/62 (8.06%)	6	2/62 (3.23%)	3	1/62 (1.61%)	1
Bronchitis † 1	2/62 (3.23%)	3	2/64 (3.13%)	3	4/62 (6.45%)	4	2/62 (3.23%)	2	1/62 (1.61%)	1
Sinusitis † 1	2/62 (3.23%)	3	3/64 (4.69%)	6	0/62 (0.00%)	0	4/62 (6.45%)	4	1/62 (1.61%)	1
Investigations
Hepatic enzyme increased † 1	0/62 (0.00%)	0	0/64 (0.00%)	0	1/62 (1.61%)	1	6/62 (9.68%)	6	0/62 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	4/62 (6.45%)	5	2/64 (3.13%)	2	1/62 (1.61%)	1	1/62 (1.61%)	1	0/62 (0.00%)	0
Nervous system disorders
Headache † 1	13/62 (20.97%)	16	4/64 (6.25%)	27	3/62 (4.84%)	4	3/62 (4.84%)	6	10/62 (16.13%)	10
Skin and subcutaneous tissue disorders
Urticaria † 1	0/62 (0.00%)	0	1/64 (1.56%)	1	4/62 (6.45%)	6	1/62 (1.61%)	1	2/62 (3.23%)	2
Vascular disorders
Hypertension † 1	4/62 (6.45%)	4	2/64 (3.13%)	2	3/62 (4.84%)	4	3/62 (4.84%)	3	1/62 (1.61%)	1
1 Term from vocabulary, MedDRA (20.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Publication of any results from this study will be according to the principles of the Declaration of Helsinki, in particular point 30, and will require prior review and written agreement of the Sponsor.

Results Point of Contact

• Name/Title: Medical Monitor
• Organization: Ablynx
• Phone: +32 (9) 262 00 00
• EMail: clinicaltrials@ablynx.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

• Responsible Party: Ablynx, a Sanofi company
• ClinicalTrials.gov Identifier: NCT02437890
• Other Study ID Numbers: ALX0061-C204; 2015-000372-95 ( EudraCT Number )
• First Submitted: April 29, 2015
• First Posted: May 8, 2015
• Results First Submitted: November 16, 2018
• Results First Posted: February 6, 2019
• Last Update Posted: February 26, 2019