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Clinical Trial Results:
A Phase II Multicenter, Randomized, Double-blind, Placebo controlled, Dose-range Finding Study to Evaluate the Safety and Efficacy of ALX-0061 Administered Subcutaneously in Subjects with Moderate to Severe Active Systemic Lupus Erythematosus

Summary
EudraCT number	2015-000372-95
Trial protocol	CZ DE PT HU ES
Global end of trial date	25 Jan 2018

Results information
Results version number	v1(current)
This version publication date	01 Dec 2018
First version publication date	01 Dec 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

ALX0061-C204

ISRCTN number

US NCT number

NCT02437890

WHO universal trial number (UTN)

Sponsor organisation name

Ablynx NV

Sponsor organisation address

Technologiepark 21, Zwijnaarde, Belgium, 9052

Public contact

Medical Monitor, Ablynx, +32 (0)9 262 00 00, clinicaltrials@ablynx.com

Scientific contact

Medical Monitor, Ablynx, +32 (0)9 262 00 00, clinicaltrials@ablynx.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

08 Mar 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

25 Jan 2018

Global end of trial reached?

Yes

Global end of trial date

25 Jan 2018

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy and safety of different dose regimens of ALX-0061 administered subcutaneously (s.c.) to subjects with moderate to severe active, seropositive systemic lupus erythematosus (SLE) compared to placebo.

Protection of trial subjects

Only subjects who met all the study inclusion criteria and none of the exclusion criteria were to be randomized to study treatment. All subjects were free to withdraw from the clinical study at any time for any reason. Close monitoring of all subjects was to be adhered to throughout the study.

Background therapy

Standard of care therapy for SLE. The dose of oral corticosteroids (equivalent to ≤25 mg of prednisone/day) was to be stable for at least 4 weeks prior to baseline. If the subject had started immunosuppressants prior to first dosing and was still taking this medication at baseline: azathioprine (maximum 150 mg/day), mycophenolate mofetil (maximum 2.0 g/day), methotrexate (MTX) (maximum 25 mg/week), cyclosporine (maximum 200 mg/day), leflunomide (maximum 20 mg/day), treatment duration had to be at least 12 weeks with a stable dose for at least 4 weeks prior to baseline; either alone or in combination with corticosteroids and/or hydroxychloroquine.

Evidence for comparator

Not applicable

Actual start date of recruitment

02 Jul 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 23

Country: Number of subjects enrolled

Portugal: 6

Country: Number of subjects enrolled

Spain: 8

Country: Number of subjects enrolled

Czech Republic: 6

Country: Number of subjects enrolled

Germany: 2

Country: Number of subjects enrolled

Hungary: 14

Country: Number of subjects enrolled

Argentina: 18

Country: Number of subjects enrolled

Chile: 2

Country: Number of subjects enrolled

Korea, Republic of: 5

Country: Number of subjects enrolled

Mexico: 26

Country: Number of subjects enrolled

Peru: 6

Country: Number of subjects enrolled

Philippines: 13

Country: Number of subjects enrolled

Russian Federation: 28

Country: Number of subjects enrolled

Serbia: 63

Country: Number of subjects enrolled

Taiwan: 7

Country: Number of subjects enrolled

Ukraine: 33

Country: Number of subjects enrolled

United States: 52

Worldwide total number of subjects

312

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

312

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 312 subjects was 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.

Screening 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.

Period 1 title

Overall Study Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

Study drug treatment allocation was double blind. As the highest dose of vobarilizumab (ALX-0061 225 mg q2w) exceeded the volume that could be administered in a single injection, subjects in the other 4 treatment groups were also administered 2 injections with 1 or both syringes containing placebo, depending on the assigned treatment group to maintain the blind. Blinding was maintained until the last subject enrolled completed the final evaluations and the database was locked.

Are arms mutually exclusive

Yes

Placebo

Arm description

Two s.c. injections with placebo every 2 weeks (q2w)

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

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 q4w

Arm description

ALX-0061 75 mg every 4 weeks (q4w)

Arm type

Experimental

Investigational medicinal product name

ALX-0061

Investigational medicinal product code

Other name

ALX-0061 Nanobody

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

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, subjecs 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 q4w

Arm description

ALX-0061 150 mg every 4 weeks (q4w)

Arm type

Experimental

Investigational medicinal product name

ALX-0061

Investigational medicinal product code

Other name

ALX-0061 Nanobody

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

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, subjecs 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 q2w

Arm description

ALX-0061 150 mg every 2 weeks (q2w)

Arm type

Experimental

Investigational medicinal product name

ALX-0061

Investigational medicinal product code

Other name

ALX-0061 Nanobody

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

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, subjecs 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 q2w

Arm description

ALX-0061 225 mg every 2 weeks (q2w)

Arm type

Experimental

Investigational medicinal product name

ALX-0061

Investigational medicinal product code

Other name

ALX-0061 Nanobody

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

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, subjecs 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.

Number of subjects in period 1	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Started	62	64	62	62	62
Completed	54	48	47	40	46
Not completed	8	16	15	22	16
Sponsor's decision	1	1	4	-	2
Adverse event, serious fatal	-	-	-	2	-
Consent withdrawn by subject	1	2	6	5	5
Physician decision	-	-	-	1	-
Adverse event, non-fatal	4	9	5	11	7
Other	1	-	-	-	-
Non-compliance to study drug	-	1	-	-	1
Lack of efficacy	1	3	-	3	1

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Two s.c. injections with placebo every 2 weeks (q2w)

Reporting group title

ALX-0061 75 mg q4w

Reporting group description

ALX-0061 75 mg every 4 weeks (q4w)

Reporting group title

ALX-0061 150 mg q4w

Reporting group description

ALX-0061 150 mg every 4 weeks (q4w)

Reporting group title

ALX-0061 150 mg q2w

Reporting group description

ALX-0061 150 mg every 2 weeks (q2w)

Reporting group title

ALX-0061 225 mg q2w

Reporting group description

ALX-0061 225 mg every 2 weeks (q2w)

Reporting group values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w	Total
Number of subjects	62	64	62	62	62	312
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	62	64	62	62	62	312
From 65-84 years	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	42.3 ( 10.11 )	42.0 ( 11.00 )	41.8 ( 10.79 )	39.2 ( 11.58 )	42.0 ( 10.44 )	-
Gender categorical
Units: Subjects
Female	60	61	61	61	57	300
Male	2	3	1	1	5	12

End points

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Reporting group title

Placebo

Reporting group description

Two s.c. injections with placebo every 2 weeks (q2w)

Reporting group title

ALX-0061 75 mg q4w

Reporting group description

ALX-0061 75 mg every 4 weeks (q4w)

Reporting group title

ALX-0061 150 mg q4w

Reporting group description

ALX-0061 150 mg every 4 weeks (q4w)

Reporting group title

ALX-0061 150 mg q2w

Reporting group description

ALX-0061 150 mg every 2 weeks (q2w)

Reporting group title

ALX-0061 225 mg q2w

Reporting group description

ALX-0061 225 mg every 2 weeks (q2w)

Primary: 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

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End point title

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

End point 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 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: 1. BILAG-2004 normal improvement: all A scores at Baseline improved to B, C or D, and all B scores improved to C or D. 2. No worsening in disease activity: no new BILAG-2004 A scores and ≤ 1 new increase to B. 3. No worsening of total mSLEDAI-2K score from Baseline. 4. No significant deterioration (< 10% worsening from Baseline) in PGA. 5. No treatment failure (including the premature discontinuation from study treatment).

End point type

Primary

End point timeframe

At Week 24 visit

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[1]	64 ^[2]	62 ^[3]	62 ^[4]	62 ^[5]
Units: Percent responders	47	44	39	39	37

Notes
[1] - mITT Population - Non-response imputation (NRI)
[2] - mITT Population - NRI
[3] - mITT Population - NRI
[4] - mITT Population - NRI
[5] - mITT Population - NRI

Multiple Contrast Test - Linear model

Statistical analysis description

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.

Comparison groups

Placebo v ALX-0061 75 mg q4w v ALX-0061 150 mg q4w v ALX-0061 150 mg q2w v ALX-0061 225 mg q2w

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.526

Method

Multiple Contrast Test

Confidence interval

Multiple Contrast Test - Emax model

Statistical analysis description

Comparison groups

Placebo v ALX-0061 75 mg q4w v ALX-0061 150 mg q4w v ALX-0061 150 mg q2w v ALX-0061 225 mg q2w

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.504

Method

Multiple Contrast Test

Confidence interval

Multiple Contrast Test - Logistic model

Statistical analysis description

Comparison groups

Placebo v ALX-0061 75 mg q4w v ALX-0061 150 mg q4w v ALX-0061 150 mg q2w v ALX-0061 225 mg q2w

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.548

Method

Multiple Contrast Test

Confidence interval

Multiple Contrast Test - 1st Beta model

Statistical analysis description

Comparison groups

Placebo v ALX-0061 75 mg q4w v ALX-0061 150 mg q4w v ALX-0061 150 mg q2w v ALX-0061 225 mg q2w

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.985

Method

Multiple Contrast Test

Confidence interval

Multiple Contrast Test - 2nd Beta model

Statistical analysis description

Comparison groups

Placebo v ALX-0061 75 mg q4w v ALX-0061 150 mg q4w v ALX-0061 150 mg q2w v ALX-0061 225 mg q2w

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.524

Method

Multiple Contrast Test

Confidence interval

Secondary: Proportion of subjects with mBICLA response at Week 24 and Week 48

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End point title

Proportion of subjects with mBICLA response at Week 24 and Week 48

End point description

Proportion of mBICLA responders at Week 24 and Week 48

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[6]	64 ^[7]	62 ^[8]	62 ^[9]	62 ^[10]
Units: Percent responders
Week 24	46	44	38	39	36
Week 48	48	53	37	32	37

Notes
[6] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 61 Week 48: n = 59
[7] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 64 Week 48: n = 61
[8] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 58 Week 48: n = 60
[9] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 62 Week 48: n = 60
[10] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 61 Week 48: n = 60

No statistical analyses for this end point

Secondary: Proportion of subjects with modified Systemic Lupus Erythematosus Responder Index (mSRI-4) response at Week 24 and Week 48

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End point title

Proportion of subjects with modified Systemic Lupus Erythematosus Responder Index (mSRI-4) response at Week 24 and Week 48

End point description

Proportion of mSRI-4 responders at Week 24 and Week 48 Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[11]	64 ^[12]	62 ^[13]	62 ^[14]	62 ^[15]
Units: Percent responders
Week 24	63	62	52	54	48
Week 48	59	60	49	45	55

Notes
[11] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 59 Week 48: n = 58
[12] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 63 Week 48: n = 60
[13] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 58 Week 48: n = 59
[14] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 61 Week 48: n = 58
[15] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 60 Week 48: n = 60

No statistical analyses for this end point

Secondary: Proportion of subjects with mSRI-5 response at Week 24 and Week 48

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End point title

Proportion of subjects with mSRI-5 response at Week 24 and Week 48

End point description

Proportion of mSRI-5 responders at Week 24 and Week 48 Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[16]	64 ^[17]	62 ^[18]	62 ^[19]	62 ^[20]
Units: Percent responders
Week 24	30	39	35	34	28
Week 48	36	48	33	29	38

Notes
[16] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 57 Week 48: n = 56
[17] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 61 Week 48: n = 58
[18] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 55
[19] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 59 Week 48: n = 56
[20] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 58 Week 48: n = 58

No statistical analyses for this end point

Secondary: Proportion of subjects with mSRI-6 response at Week 24 and Week 48

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End point title

Proportion of subjects with mSRI-6 response at Week 24 and Week 48

End point description

Proportion of mSRI-6 responders at Week 24 and Week 48 Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[21]	64 ^[22]	62 ^[23]	62 ^[24]	62 ^[25]
Units: Percent responders
Week 24	28	38	35	32	26
Week 48	36	48	29	29	38

Notes
[21] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 57 Week 48: n = 56
[22] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 61 Week 48: n = 58
[23] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 55
[24] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 59 Week 48: n = 56
[25] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 58 Week 48: n = 58

No statistical analyses for this end point

Secondary: Proportion of subjects with mSRI-7 response at Week 24 and Week 48

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End point title

Proportion of subjects with mSRI-7 response at Week 24 and Week 48

End point description

Proportion of mSRI-7 responders at Week 24 and Week 48 Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[26]	64 ^[27]	62 ^[28]	62 ^[29]	62 ^[30]
Units: Percent responders
Week 24	20	17	21	24	16
Week 48	26	31	18	17	21

Notes
[26] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 46 Week 48: n = 46
[27] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 47 Week 48: n = 45
[28] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 39 Week 48: n = 40
[29] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 50 Week 48: n = 47
[30] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 43 Week 48: n = 42

No statistical analyses for this end point

Secondary: Proportion of subjects with mSRI-8 response at Week 24 and Week 48

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End point title

Proportion of subjects with mSRI-8 response at Week 24 and Week 48

End point description

Proportion of mSRI-8 responders at Week 24 and Week 48 Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[31]	64 ^[32]	62 ^[33]	62 ^[34]	62 ^[35]
Units: Percent responders
Week 24	20	15	22	20	17
Week 48	24	31	18	15	20

Notes
[31] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 45 Week 48: n = 45
[32] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 47 Week 48: n = 45
[33] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 37 Week 48: n = 38
[34] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 46
[35] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 42 Week 48: n = 41

No statistical analyses for this end point

Secondary: Change from baseline in modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) score at Week 24 and Week 48

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End point title

Change from baseline in modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) score at Week 24 and Week 48

End point description

Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline mSLEDAI-2K Score and geographic region as covariates A negative change from baseline reflects an improvement

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[36]	64 ^[37]	62 ^[38]	62 ^[39]	62 ^[40]
Units: not applicable
arithmetic mean (standard error)
Week 24	-4.0 ( 0.42 )	-4.6 ( 0.43 )	-3.8 ( 0.43 )	-4.3 ( 0.44 )	-3.6 ( 0.44 )
Week 48	-4.5 ( 0.40 )	-5.2 ( 0.43 )	-4.3 ( 0.42 )	-4.9 ( 0.48 )	-4.9 ( 0.44 )

Notes
[36] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 53 Week 48: n = 51
[37] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 50 Week 48: n = 46
[38] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 51 Week 48: n = 47
[39] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 48 Week 48: n = 36
[40] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 51 Week 48: n = 45

No statistical analyses for this end point

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement at Week 24 and Week 48

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End point title

Proportion of subjects with BILAG-2004 Normal Improvement at Week 24 and Week 48

End point 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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[41]	64 ^[42]	62 ^[43]	62 ^[44]	62 ^[45]
Units: Percent responders
Week 24	55	56	50	51	44
Week 48	63	71	58	56	54

Notes
[41] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[42] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[43] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[44] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[45] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 46

No statistical analyses for this end point

Secondary: Proportion of subjects with BILAG-2004 Enhanced Improvement at Week 24 and Week 48

Top of page

End point title

Proportion of subjects with BILAG-2004 Enhanced Improvement at Week 24 and Week 48

End point 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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[46]	64 ^[47]	62 ^[48]	62 ^[49]	62 ^[50]
Units: Percent responders
Week 24	13	31	20	12	24
Week 48	9	21	14	15	16

Notes
[46] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[47] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[48] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[49] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[50] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 45

No statistical analyses for this end point

Secondary: BILAG-2004 Total Score at Baseline, Week 24 and Week 48

Top of page

End point title

BILAG-2004 Total Score at Baseline, Week 24 and Week 48

End point description

End point type

Secondary

End point timeframe

At Baseline, Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[51]	64 ^[52]	62 ^[53]	62 ^[54]	62 ^[55]
Units: not applicable
arithmetic mean (standard error)
Baseline	17.4 ( 0.78 )	17.9 ( 0.69 )	15.2 ( 0.68 )	17.4 ( 0.71 )	17.3 ( 0.82 )
Week 24	6.8 ( 0.78 )	5.7 ( 0.79 )	7.0 ( 0.76 )	7.2 ( 0.94 )	7.4 ( 0.84 )
Week 48	6.0 ( 0.73 )	4.0 ( 0.72 )	5.2 ( 0.74 )	6.0 ( 0.92 )	6.2 ( 0.91 )

Notes
[51] - mITT Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 56 Week 48: n = 53
[52] - mITT Population Number of subjects at visit: Baseline: n = 64 Week 24: n = 52 Week 48: n = 48
[53] - mITT Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 56 Week 48: n = 50
[54] - mITT Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 49 Week 48: n = 39
[55] - mITT Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 54 Week 48: n = 45

No statistical analyses for this end point

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement in mucocutaneous system at Week 24 and Week 48

Top of page

End point title

Proportion of subjects with BILAG-2004 Normal Improvement in mucocutaneous system at Week 24 and Week 48

End point 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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[56]	64 ^[57]	62 ^[58]	62 ^[59]	62 ^[60]
Units: Percent responders
Week 24	53	53	42	49	53
Week 48	58	66	49	53	55

Notes
[56] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 47 Week 48: n = 45
[57] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 45 Week 48: n = 41
[58] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 43 Week 48: n = 37
[59] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 43 Week 48: n = 34
[60] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 47 Week 48: n = 40

No statistical analyses for this end point

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement in musculoskeletal system at Week 24 and Week 48

Top of page

End point title

Proportion of subjects with BILAG-2004 Normal Improvement in musculoskeletal system at Week 24 and Week 48

End point description

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[61]	64 ^[62]	62 ^[63]	62 ^[64]	62 ^[65]
Units: Percent responders
Week 24	87	89	84	80	73
Week 48	89	95	88	89	82

Notes
[61] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 47 Week 48: n = 45
[62] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 44 Week 48: n = 40
[63] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 43 Week 48: n = 40
[64] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 45 Week 48: n = 37
[65] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 45 Week 48: n = 38

No statistical analyses for this end point

Secondary: Proportion of subjects with persistent minimal or no activity in 9 organ systems according to BILAG-2004 Systems Tally at Week 24 and Week 48

Top of page

End point title

Proportion of subjects with persistent minimal or no activity in 9 organ systems according to BILAG-2004 Systems Tally at Week 24 and Week 48

End point description

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[66]	64 ^[67]	62 ^[68]	62 ^[69]	62 ^[70]
Units: Percent responders
Week 24	27	46	34	33	30
Week 48	37	56	46	41	41

Notes
[66] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[67] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[68] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[69] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[70] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48

Top of page

End point title

Change from baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48

End point description

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.

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[71]	64 ^[72]	62 ^[73]	62 ^[74]	62 ^[75]
Units: not applicable
arithmetic mean (standard error)
Week 24	-25.2 ( 2.03 )	-28.4 ( 2.09 )	-26.2 ( 2.04 )	-23.5 ( 2.16 )	-22.7 ( 2.08 )
Week 48	-28.3 ( 1.73 )	-32.9 ( 1.82 )	-30.2 ( 1.82 )	-30.1 ( 2.00 )	-30.5 ( 1.87 )

Notes
[71] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[72] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[73] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 55 Week 48: n = 48
[74] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[75] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in Patient's Global Assessment at Week 24 and Week 48

Top of page

End point title

Change from baseline in Patient's Global Assessment at Week 24 and Week 48

End point description

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.

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[76]	64 ^[77]	62 ^[78]	62 ^[79]	62 ^[80]
Units: not applicable
arithmetic mean (standard error)
Week 24	-12.4 ( 2.87 )	-13.5 ( 2.96 )	-14.9 ( 2.87 )	-20.1 ( 3.05 )	-16.0 ( 2.98 )
Week 48	-15.1 ( 2.70 )	-21.5 ( 2.87 )	-22.1 ( 2.82 )	-27.2 ( 3.12 )	-25.9 ( 2.94 )

Notes
[76] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[77] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[78] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 49
[79] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[80] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in proteinuria at Week 24 and Week 48

Top of page

End point title

Change from baseline in proteinuria at Week 24 and Week 48

End point 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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[81]	64 ^[82]	62 ^[83]	62 ^[84]	62 ^[85]
Units: g/mol
arithmetic mean (standard error)
Week 24	6.17 ( 3.730 )	1.77 ( 3.847 )	1.03 ( 3.735 )	-3.02 ( 3.876 )	0.16 ( 3.962 )
Week 48	4.89 ( 5.732 )	3.83 ( 6.152 )	-1.62 ( 5.761 )	-0.49 ( 6.582 )	-1.21 ( 6.191 )

Notes
[81] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 48 Week 48: n = 43
[82] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 44 Week 48: n = 37
[83] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 48 Week 48: n = 42
[84] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 42 Week 48: n = 30
[85] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 42 Week 48: n = 36

No statistical analyses for this end point

Secondary: Number of subjects who were treatment-emergent urine sediment positive at Week 24 and Week 48

Top of page

End point title

Number of subjects who were treatment-emergent urine sediment positive at Week 24 and Week 48

End point 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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[86]	64 ^[87]	62 ^[88]	62 ^[89]	62 ^[90]
Units: Number of subjects
Week 24	1	0	0	0	0
Week 48	0	0	0	0	0

Notes
[86] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[87] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[88] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[89] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[90] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in serum creatinine at Week 24 and Week 48

Top of page

End point title

Change from baseline in serum creatinine at Week 24 and Week 48

End point 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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[91]	64 ^[92]	62 ^[93]	62 ^[94]	62 ^[95]
Units: umol/L
arithmetic mean (standard error)
Week 24	-1.25 ( 2.172 )	-3.29 ( 2.237 )	-1.50 ( 2.182 )	-3.98 ( 2.309 )	-0.86 ( 2.276 )
Week 48	1.19 ( 2.016 )	-1.87 ( 2.152 )	-6.26 ( 2.085 )	-4.04 ( 2.359 )	-1.24 ( 2.199 )

Notes
[91] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[92] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 47
[93] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[94] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 38
[95] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48

Top of page

End point title

Change from baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48

End point 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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[96]	64 ^[97]	62 ^[98]	62 ^[99]	62 ^[100]
Units: mL/min/1.73m2
arithmetic mean (standard error)
Week 24	-1.63 ( 2.869 )	4.83 ( 2.931 )	-1.72 ( 2.854 )	-0.90 ( 3.044 )	-8.91 ( 3.014 )
Week 48	-6.00 ( 3.052 )	2.47 ( 3.231 )	4.66 ( 3.125 )	-1.47 ( 3.562 )	-8.08 ( 3.326 )

Notes
[96] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 55 Week 48: n = 53
[97] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 47
[98] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[99] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 38
[100] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Percentage treatment failures from Baseline to Week 24 and Week 48

Top of page

End point title

Percentage treatment failures from Baseline to Week 24 and Week 48

End point description

Defined as non-protocol allowed increase in steroid dose, start i.v. or i.m. steroids, or start or increase of immunosuppressant

End point type

Secondary

End point timeframe

From Baseline to Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[101]	64 ^[102]	62 ^[103]	62 ^[104]	62 ^[105]
Units: Percent treatment failures
Baseline to Week 24	3	0	7	3	5
Baseline to Week 48	8	2	15	10	10

Notes
[101] - mITT Population
[102] - mITT Population
[103] - mITT Population
[104] - mITT Population
[105] - mITT Population

No statistical analyses for this end point

Secondary: Proportion of subjects experiencing severe flares according to BILAG-2004 Flare Index from Baseline to Week 24 and Week 48

Top of page

End point title

Proportion of subjects experiencing severe flares according to BILAG-2004 Flare Index from Baseline to Week 24 and Week 48

End point description

End point type

Secondary

End point timeframe

From Baseline to Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[106]	64 ^[107]	62 ^[108]	62 ^[109]	62 ^[110]
Units: Percent
Baseline to Week 24	13	9	10	11	10
Baseline to Week 48	13	9	16	15	15

Notes
[106] - mITT Population
[107] - mITT Population
[108] - mITT Population
[109] - mITT Population
[110] - mITT Population

No statistical analyses for this end point

Secondary: Proportion of subjects experiencing severe flares according to mSLEDAI-2K Flare Index (mSFI) from Baseline to Week 24 and Week 48

Top of page

End point title

Proportion of subjects experiencing severe flares according to mSLEDAI-2K Flare Index (mSFI) from Baseline to Week 24 and Week 48

End point description

End point type

Secondary

End point timeframe

From baseline to Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[111]	64 ^[112]	62 ^[113]	62 ^[114]	62 ^[115]
Units: Percent
Baseline to Week 24	2	0	3	3	2
Baseline to Week 48	6	0	6	6	3

Notes
[111] - mITT Population
[112] - mITT Population
[113] - mITT Population
[114] - mITT Population
[115] - mITT Population

No statistical analyses for this end point

Secondary: Percent change from baseline in daily dose of steroids at Week 24 and Week 48

Top of page

End point title

Percent change from baseline in daily dose of steroids at Week 24 and Week 48

End point 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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[116]	64 ^[117]	62 ^[118]	62 ^[119]	62 ^[120]
Units: percent
arithmetic mean (standard error)
Week 24	3.87 ( 2.781 )	-0.80 ( 2.922 )	0.25 ( 2.689 )	-1.40 ( 2.940 )	-3.46 ( 2.831 )
Week 48	6.93 ( 5.047 )	-3.22 ( 5.397 )	-1.03 ( 5.050 )	-2.32 ( 5.758 )	-1.73 ( 5.521 )

Notes
[116] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 48 Week 48: n = 46
[117] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 43 Week 48: n = 40
[118] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 51 Week 48: n = 45
[119] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 43 Week 48: n = 34
[120] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 48 Week 48: n = 40

No statistical analyses for this end point

Secondary: Proportion of subjects whose daily dose of steroids was reduced without severe flares during Weeks 40-48

Top of page

End point title

Proportion of subjects whose daily dose of steroids was reduced without severe flares during Weeks 40-48

End point description

Proportion 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.

End point type

Secondary

End point timeframe

Between Week 40 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	34 ^[121]	36 ^[122]	30 ^[123]	32 ^[124]	36 ^[125]
Units: Percent
BILAG-2004-defined Flare	9	6	17	3	8
mSFI-defined Flare	9	6	13	3	11

Notes
[121] - mITT Population
[122] - mITT Population
[123] - mITT Population
[124] - mITT Population
[125] - mITT Population

No statistical analyses for this end point

Secondary: Proportion of subjects who discontinued Prednisone (or equivalent) by Week 48 without experiencing a severe flare

Top of page

End point title

Proportion of subjects who discontinued Prednisone (or equivalent) by Week 48 without experiencing a severe flare

End point description

Proportion of subjects who discontinued Prednisone (or equivalent) by Week 48 without experiencing a BILAG-2004-defined or mSFI-defined severe flare

End point type

Secondary

End point timeframe

Up to and including Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	54 ^[126]	52 ^[127]	55 ^[128]	54 ^[129]	56 ^[130]
Units: Percent
BILAG-2004-defined flare	0	0	2	2	0
mSFI-defined flare	0	0	4	2	0

Notes
[126] - mITT Population
[127] - mITT Population
[128] - mITT Population
[129] - mITT Population
[130] - mITT Population

No statistical analyses for this end point

Secondary: Change from baseline in physical component scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48

Top of page

End point title

Change from baseline in physical component scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48

End point description

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.

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[131]	64 ^[132]	62 ^[133]	62 ^[134]	62 ^[135]
Units: not applicable
arithmetic mean (standard error)
Week 24	4.71 ( 1.241 )	4.56 ( 1.286 )	6.77 ( 1.242 )	4.67 ( 1.321 )	5.01 ( 1.292 )
Week 48	3.73 ( 1.414 )	6.97 ( 1.510 )	8.67 ( 1.460 )	8.62 ( 1.633 )	8.85 ( 1.535 )

Notes
[131] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[132] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[133] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[134] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[135] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in mental component scores of SF-36 at Week 24 and Week 48

Top of page

End point title

Change from baseline in mental component scores of SF-36 at Week 24 and Week 48

End point description

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[136]	64 ^[137]	62 ^[138]	62 ^[139]	62 ^[140]
Units: not applicable
arithmetic mean (standard error)
Week 24	0.08 ( 0.703 )	-0.99 ( 0.724 )	-0.56 ( 0.703 )	0.45 ( 0.749 )	-1.18 ( 0.732 )
Week 48	1.50 ( 0.716 )	-0.58 ( 0.756 )	-0.07 ( 0.737 )	-1.07 ( 0.827 )	-2.02 ( 0.777 )

Notes
[136] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[137] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[138] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[139] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[140] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in 28 joint count swollenness (SJC28) score at Week 24 and Week 48

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End point title

Change from baseline in 28 joint count swollenness (SJC28) score at Week 24 and Week 48

End point description

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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[141]	64 ^[142]	62 ^[143]	62 ^[144]	62 ^[145]
Units: not applicable
arithmetic mean (standard error)
Week 24	-4.8 ( 0.31 )	-5.0 ( 0.32 )	-4.9 ( 0.31 )	-4.8 ( 0.33 )	-4.5 ( 0.32 )
Week 48	-5.0 ( 0.28 )	-5.4 ( 0.30 )	-4.7 ( 0.29 )	-5.1 ( 0.32 )	-4.5 ( 0.30 )

Notes
[141] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[142] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[143] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[144] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[145] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in 28 joint count tenderness (TJC28) score at Week 24 and Week 48

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End point title

Change from baseline in 28 joint count tenderness (TJC28) score at Week 24 and Week 48

End point description

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

End point type

Secondary

End point timeframe

At Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[146]	64 ^[147]	62 ^[148]	62 ^[149]	62 ^[150]
Units: not applicable
arithmetic mean (standard error)
Week 24	-6.8 ( 0.49 )	-6.8 ( 0.50 )	-6.4 ( 0.49 )	-5.8 ( 0.52 )	-5.5 ( 0.50 )
Week 48	-6.6 ( 0.43 )	-7.4 ( 0.46 )	-6.4 ( 0.45 )	-6.6 ( 0.50 )	-6.5 ( 0.47 )

Notes
[146] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 54
[147] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 52 Week 48: n = 48
[148] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 56 Week 48: n = 50
[149] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 49 Week 48: n = 39
[150] - mITT Population Number of subjects (n) evaluated at the visit: Week 24: n = 54 Week 48: n = 46

No statistical analyses for this end point

Secondary: Change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48

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End point title

Change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48

End point description

Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline CLASI Activity Score and geographic region as covariates. A negative change denotes an improvement.

End point type

Secondary

End point timeframe

At Week 12, Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[151]	64 ^[152]	62 ^[153]	62 ^[154]	62 ^[155]
Units: not applicable
arithmetic mean (standard error)
Week 12	-2.4 ( 0.53 )	-1.9 ( 0.57 )	-1.4 ( 0.65 )	-1.6 ( 0.63 )	-1.3 ( 0.57 )
Week 24	-1.1 ( 0.53 )	-2.1 ( 0.60 )	-1.6 ( 0.66 )	-1.3 ( 0.65 )	-1.8 ( 0.57 )
Week 48	-1.3 ( 0.59 )	-3.0 ( 0.70 )	-2.5 ( 0.73 )	-2.1 ( 0.80 )	-3.0 ( 0.64 )

Notes
[151] - mITT Population Number of subjects at visit: Week 12: n = 26 Week 24: n = 25 Week 48: n = 24
[152] - mITT Population Number of subjects at visit: Week 12: n = 25 Week 24: n = 21 Week 48: n = 18
[153] - mITT Population Number of subjects at visit: Week 12: n = 18 Week 24: n = 17 Week 48: n = 16
[154] - mITT Population Number of subjects at visit: Week 12: n = 21 Week 24: n = 19 Week 48: n = 14
[155] - mITT Population Number of subjects at visit: Week 12: n = 24 Week 24: n = 23 Week 48: n = 21

No statistical analyses for this end point

Secondary: Change from baseline in CLASI Damage Score at Week 12, Week 24 and Week 48

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End point title

Change from baseline in CLASI Damage Score at Week 12, Week 24 and Week 48

End point description

Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline CLASI Damage Score and geographic region as covariates A negative change denotes an improvement

End point type

Secondary

End point timeframe

At Week 12, Week 24 and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[156]	64 ^[157]	62 ^[158]	62 ^[159]	62 ^[160]
Units: not applicable
arithmetic mean (standard error)
Week 12	0.1 ( 0.49 )	0.1 ( 0.47 )	-0.1 ( 0.59 )	-0.3 ( 0.52 )	-0.4 ( 0.52 )
Week 24	0.4 ( 0.61 )	-0.4 ( 0.61 )	-0.4 ( 0.73 )	0.3 ( 0.67 )	-0.1 ( 0.66 )
Week 48	0.0 ( 0.57 )	-0.1 ( 0.60 )	-0.3 ( 0.68 )	0.4 ( 0.68 )	-0.7 ( 0.63 )

Notes
[156] - mITT Population Number of subjects at visit: Week 12: n = 11 Week 24: n = 11 Week 48: n = 11
[157] - mITT Population Number of subjects at visit: Week 12: n = 14 Week 24: n = 11 Week 48: n = 9
[158] - mITT Population Number of subjects at visit: Week 12: n = 8 Week 24: n = 8 Week 48: n = 8
[159] - mITT Population Number of subjects at visit: Week 12: n = 13 Week 24: n = 11 Week 48: n = 8
[160] - mITT Population Number of subjects at visit: Week 12: n = 13 Week 24: n = 12 Week 48: n = 11

No statistical analyses for this end point

Secondary: ALX-0061 Serum Concentrations at Week 24 and Week 48

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End point title

ALX-0061 Serum Concentrations at Week 24 and Week 48 ^[161]

End point description

End point type

Secondary

End point timeframe

At Week 24 and Week 48

Notes
[161] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: PK was only measured in active treatment groups.

End point values	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	64 ^[162]	62 ^[163]	62 ^[164]	62 ^[165]
Units: µg/mL
geometric mean (geometric coefficient of variation)
Week 24	0.118 ( 2.29 )	2.05 ( 3.89 )	18.1 ( 1.60 )	30.7 ( 1.62 )
Week 48	0.155 ( 3.28 )	2.17 ( 3.45 )	17.9 ( 1.71 )	36.1 ( 1.46 )

Notes
[162] - Safety Population Number of subjects (n) evaluated at the visit: Week 24: n = 43 Week 48: n = 33
[163] - Safety Population Number of subjects (n) evaluated at the visit: Week 24: n = 53 Week 48: n = 43
[164] - Safety Population Number of subjects (n) evaluated at the visit: Week 24: n = 47 Week 48: n = 32
[165] - Safety Population Number of subjects (n) evaluated at the visit: Week 24: n = 50 Week 48: n = 42

No statistical analyses for this end point

Secondary: Actual values of soluble Interleukin 6 Receptor (sIL-6R) concentrations at Baseline, Week 24, and Week 48

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End point title

Actual values of soluble Interleukin 6 Receptor (sIL-6R) concentrations at Baseline, Week 24, and Week 48

End point description

End point type

Secondary

End point timeframe

At Baseline, Week 24, and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[166]	64 ^[167]	62 ^[168]	62 ^[169]	62 ^[170]
Units: ng/mL
arithmetic mean (standard error)
Baseline	42.22 ( 2.496 )	37.63 ( 1.933 )	38.10 ( 1.895 )	42.14 ( 3.366 )	36.92 ( 1.810 )
Week 24	39.70 ( 1.934 )	198.26 ( 18.856 )	603.51 ( 31.678 )	668.57 ( 25.568 )	634.49 ( 23.638 )
Week 48	39.41 ( 2.270 )	224.66 ( 25.515 )	610.86 ( 29.445 )	650.73 ( 38.516 )	659.79 ( 32.862 )

Notes
[166] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 55 Week 48: n = 53
[167] - Safety Population Number of subjects at visit: Baseline: n = 63 Week 24: n = 51 Week 48: n = 47
[168] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 54 Week 48: n = 50
[169] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 49 Week 48: n = 38
[170] - Safety Population Number of subjects at visit: Baseline: n = 60 Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Actual values of C-reactive protein (CRP) concentrations at Baseline, Week 24, and Week 48

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End point title

Actual values of C-reactive protein (CRP) concentrations at Baseline, Week 24, and Week 48

End point description

End point type

Secondary

End point timeframe

At Baseline, Week 24, and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[171]	64 ^[172]	62 ^[173]	62 ^[174]	62 ^[175]
Units: nmol/L
arithmetic mean (standard error)
Baseline	43.58 ( 9.527 )	49.05 ( 12.924 )	38.89 ( 8.394 )	66.32 ( 17.221 )	32.23 ( 4.957 )
Week 24	59.43 ( 11.277 )	47.22 ( 9.607 )	26.08 ( 9.995 )	3.83 ( 0.668 )	3.20 ( 0.357 )
Week 48	30.70 ( 4.709 )	37.65 ( 8.647 )	23.20 ( 6.705 )	4.41 ( 0.988 )	4.02 ( 0.962 )

Notes
[171] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 56 Week 48: n = 54
[172] - Safety Population Number of subjects at visit: Baseline: n = 64 Week 24: n = 52 Week 48: n = 46
[173] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 56 Week 48: n = 50
[174] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 49 Week 48: n = 38
[175] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Actual values of fibrinogen concentrations at Baseline, Week 24, and Week 48

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End point title

Actual values of fibrinogen concentrations at Baseline, Week 24, and Week 48

End point description

End point type

Secondary

End point timeframe

At Baseline, Week 24, and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[176]	64 ^[177]	62 ^[178]	62 ^[179]	62 ^[180]
Units: g/L
arithmetic mean (standard error)
Baseline	3.2 ( 0.09 )	3.2 ( 0.08 )	3.2 ( 0.09 )	3.2 ( 0.10 )	3.1 ( 0.09 )
Week 24	3.3 ( 0.08 )	3.3 ( 0.10 )	2.3 ( 0.12 )	1.9 ( 0.05 )	1.9 ( 0.05 )
Week 48	3.3 ( 0.09 )	3.3 ( 0.12 )	2.3 ( 0.11 )	1.9 ( 0.06 )	1.9 ( 0.05 )

Notes
[176] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 55 Week 48: n = 51
[177] - Safety Population Number of subjects at visit: Baseline: n = 64 Week 24: n = 52 Week 48: n = 48
[178] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 54 Week 48: n = 49
[179] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 49 Week 48: n = 36
[180] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 51 Week 48: n = 46

No statistical analyses for this end point

Secondary: Actual values of anti-double-stranded (ds) DNA concentrations at Baseline, Week 24, and Week 48

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End point title

Actual values of anti-double-stranded (ds) DNA concentrations at Baseline, Week 24, and Week 48

End point description

End point type

Secondary

End point timeframe

At Baseline, Week 24, and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[181]	64 ^[182]	62 ^[183]	62 ^[184]	62 ^[185]
Units: IU/mL
arithmetic mean (standard error)
Baseline	132.90 ( 54.467 )	145.87 ( 113.907 )	52.88 ( 17.283 )	68.92 ( 23.226 )	73.34 ( 25.940 )
Week 24	81.36 ( 30.376 )	68.27 ( 35.053 )	46.99 ( 33.534 )	14.98 ( 4.499 )	23.25 ( 6.417 )
Week 48	81.80 ( 24.143 )	59.48 ( 32.190 )	74.21 ( 48.030 )	9.13 ( 2.108 )	15.53 ( 6.069 )

Notes
[181] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 55 Week 48: n = 54
[182] - Safety Population Number of subjects at visit: Baseline: n = 64 Week 24: n = 52 Week 48: n = 48
[183] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 55 Week 48: n = 50
[184] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 49 Week 48: n = 39
[185] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Actual values of complement C3 concentrations at Baseline, Week 24, and Week 48

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End point title

Actual values of complement C3 concentrations at Baseline, Week 24, and Week 48

End point description

End point type

Secondary

End point timeframe

At Baseline, Week 24, and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[186]	64 ^[187]	62 ^[188]	62 ^[189]	62 ^[190]
Units: mg/dL
arithmetic mean (standard error)
Baseline	102.3 ( 3.82 )	100.2 ( 4.12 )	101.9 ( 3.79 )	105.8 ( 4.38 )	98.6 ( 3.98 )
Week 24	101.7 ( 4.30 )	95.7 ( 3.81 )	82.0 ( 3.68 )	75.3 ( 2.90 )	71.8 ( 2.82 )
Week 48	95.8 ( 4.25 )	93.2 ( 4.20 )	79.0 ( 3.25 )	83.2 ( 3.18 )	72.3 ( 2.61 )

Notes
[186] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 55 Week 48: n = 53
[187] - Safety Population Number of subjects at visit: Baseline: n = 64 Week 24: n = 52 Week 48: n = 48
[188] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 55 Week 48: n = 50
[189] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 47 Week 48: n = 38
[190] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 52 Week 48: n = 45

No statistical analyses for this end point

Secondary: Actual values of complement C4 concentrations at Baseline, Week 24, and Week 48

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End point title

Actual values of complement C4 concentrations at Baseline, Week 24, and Week 48

End point description

End point type

Secondary

End point timeframe

At Baseline, Week 24, and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[191]	64 ^[192]	62 ^[193]	62 ^[194]	62 ^[195]
Units: mg/dL
arithmetic mean (standard error)
Baseline	17.3 ( 1.08 )	17.8 ( 1.07 )	15.9 ( 0.96 )	18.7 ( 1.19 )	16.3 ( 1.04 )
Week 24	17.5 ( 1.09 )	17.4 ( 1.10 )	10.6 ( 0.85 )	8.7 ( 0.40 )	7.9 ( 0.37 )
Week 48	16.3 ( 1.15 )	17.3 ( 1.27 )	10.5 ( 0.84 )	9.8 ( 0.89 )	8.1 ( 0.41 )

Notes
[191] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 54 Week 48: n = 52
[192] - Safety Population Number of subjects at visit: Baseline: n = 64 Week 24: n = 52 Week 48: n = 47
[193] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 55 Week 48: n = 48
[194] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 47 Week 48: n = 38
[195] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 52 Week 48: n = 43

No statistical analyses for this end point

Secondary: Actual values for hemolytic complement component 50 (CH50) at Baseline, Week 24, and Week 48

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End point title

Actual values for hemolytic complement component 50 (CH50) at Baseline, Week 24, and Week 48

End point description

End point type

Secondary

End point timeframe

At Baseline, Week 24, and Week 48

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[196]	64 ^[197]	62 ^[198]	62 ^[199]	62 ^[200]
Units: unit(s)
arithmetic mean (standard error)
Baseline	101.1 ( 7.46 )	109.6 ( 8.83 )	98.9 ( 6.95 )	103.0 ( 7.47 )	82.4 ( 7.09 )
Week 24	95.8 ( 7.94 )	107.0 ( 7.08 )	73.6 ( 6.94 )	56.7 ( 4.91 )	41.1 ( 3.63 )
Week 48	102.2 ( 8.38 )	113.1 ( 8.63 )	73.5 ( 8.26 )	68.4 ( 6.95 )	41.9 ( 3.32 )

Notes
[196] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 56 Week 48: n = 54
[197] - Safety Population Number of subjects at visit: Baseline: n = 64 Week 24: n = 52 Week 48: n = 48
[198] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 56 Week 48: n = 50
[199] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 49 Week 48: n = 39
[200] - Safety Population Number of subjects at visit: Baseline: n = 62 Week 24: n = 53 Week 48: n = 46

No statistical analyses for this end point

Secondary: Proportion of subjects who were treatment-emergent (TE) anti-drug antibody (ADA) positive

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End point title

Proportion of subjects who were treatment-emergent (TE) anti-drug antibody (ADA) positive

End point description

End point type

Secondary

End point timeframe

From first administration of ALX-0061 up to and including follow-up

End point values	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Number of subjects analysed	62 ^[201]	64 ^[202]	62 ^[203]	62 ^[204]	62 ^[205]
Units: Percent	52	25	29	50	61

Notes
[201] - Safety Population
[202] - Safety Population
[203] - Safety Population
[204] - Safety Population
[205] - Safety Population

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From obtaining signed and dated informed consent form (ICF) until completion of the subject's last visit.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Placebo

Reporting group description

Two subcutaneous injections with placebo every two weeks

Reporting group title

ALX-0061 75 mg q4w

Reporting group description

ALX-0061 75 mg every 4 weeks

Reporting group title

ALX-0061 150 mg q4w

Reporting group description

ALX-0061 150 mg every 4 weeks

Reporting group title

ALX-0061 150 mg q2w

Reporting group description

ALX-0061 150 mg every 2 weeks

Reporting group title

ALX-0061 225 mg q2w

Reporting group description

ALX-0061 225 mg every 2 weeks

Serious adverse events	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 62 (11.29%)	2 / 64 (3.13%)	4 / 62 (6.45%)	5 / 62 (8.06%)	5 / 62 (8.06%)
number of deaths (all causes)	0	0	0	2	0
number of deaths resulting from adverse events	0	0	0	2	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vasculitis
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 62 (1.61%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Allergy to arthropod sting
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolismy
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 62 (1.61%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ligament rupture
subjects affected / exposed	1 / 62 (1.61%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament sprain
subjects affected / exposed	1 / 62 (1.61%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post-traumatic pain
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiopulmonary failure
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Nervous system disorders
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 62 (0.00%)	1 / 64 (1.56%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxic-ischaemic encephalopathy
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Blood and lymphatic system disorders
Anaemia of chronic disease
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombotic thrombocytopenic purpura
subjects affected / exposed	1 / 62 (1.61%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Open angle glaucoma
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastric ulcer
subjects affected / exposed	1 / 62 (1.61%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis chronic
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	2 / 62 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 62 (3.23%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	1 / 62 (1.61%)	0 / 64 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
subjects affected / exposed	1 / 62 (1.61%)	0 / 64 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis
subjects affected / exposed	0 / 62 (0.00%)	1 / 64 (1.56%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculoma
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tuberculous pleurisy
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	ALX-0061 75 mg q4w	ALX-0061 150 mg q4w	ALX-0061 150 mg q2w	ALX-0061 225 mg q2w
Total subjects affected by non serious adverse events
subjects affected / exposed	40 / 62 (64.52%)	41 / 64 (64.06%)	31 / 62 (50.00%)	47 / 62 (75.81%)	50 / 62 (80.65%)
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	1 / 62 (1.61%)	6 / 62 (9.68%)	0 / 62 (0.00%)
occurrences all number	0	0	1	6	0
Vascular disorders
Hypertension
subjects affected / exposed	4 / 62 (6.45%)	2 / 64 (3.13%)	3 / 62 (4.84%)	3 / 62 (4.84%)	1 / 62 (1.61%)
occurrences all number	4	2	4	3	1
Nervous system disorders
Headache
subjects affected / exposed	13 / 62 (20.97%)	4 / 64 (6.25%)	3 / 62 (4.84%)	3 / 62 (4.84%)	10 / 62 (16.13%)
occurrences all number	16	27	4	6	10
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	0 / 62 (0.00%)	2 / 64 (3.13%)	2 / 62 (3.23%)	5 / 62 (8.06%)	5 / 62 (8.06%)
occurrences all number	0	3	5	17	11
Injection site rash
subjects affected / exposed	0 / 62 (0.00%)	3 / 64 (4.69%)	1 / 62 (1.61%)	4 / 62 (6.45%)	3 / 62 (4.84%)
occurrences all number	0	3	1	17	6
Injection site reaction
subjects affected / exposed	0 / 62 (0.00%)	0 / 64 (0.00%)	0 / 62 (0.00%)	4 / 62 (6.45%)	1 / 62 (1.61%)
occurrences all number	0	0	0	5	5
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	2 / 62 (3.23%)	3 / 64 (4.69%)	3 / 62 (4.84%)	5 / 62 (8.06%)	6 / 62 (9.68%)
occurrences all number	2	6	3	9	7
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	6 / 62 (9.68%)	1 / 64 (1.56%)	0 / 62 (0.00%)	1 / 62 (1.61%)	2 / 62 (3.23%)
occurrences all number	6	1	0	1	2
Nausea
subjects affected / exposed	4 / 62 (6.45%)	1 / 64 (1.56%)	2 / 62 (3.23%)	2 / 62 (3.23%)	0 / 62 (0.00%)
occurrences all number	6	1	2	2	0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 62 (0.00%)	1 / 64 (1.56%)	4 / 62 (6.45%)	1 / 62 (1.61%)	2 / 62 (3.23%)
occurrences all number	0	1	6	1	2
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	4 / 62 (6.45%)	2 / 64 (3.13%)	1 / 62 (1.61%)	1 / 62 (1.61%)	0 / 62 (0.00%)
occurrences all number	5	2	1	1	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	8 / 62 (12.90%)	5 / 64 (7.81%)	7 / 62 (11.29%)	3 / 62 (4.84%)	8 / 62 (12.90%)
occurrences all number	11	10	10	5	12
Upper respiratory tract infection
subjects affected / exposed	5 / 62 (8.06%)	5 / 64 (7.81%)	5 / 62 (8.06%)	5 / 62 (8.06%)	3 / 62 (4.84%)
occurrences all number	5	7	5	8	5
Nasopharyngitis
subjects affected / exposed	6 / 62 (9.68%)	6 / 64 (9.38%)	5 / 62 (8.06%)	2 / 62 (3.23%)	1 / 62 (1.61%)
occurrences all number	8	7	6	3	1
Bronchitis
subjects affected / exposed	2 / 62 (3.23%)	2 / 64 (3.13%)	4 / 62 (6.45%)	2 / 62 (3.23%)	1 / 62 (1.61%)
occurrences all number	3	3	4	2	1
Sinusitis
subjects affected / exposed	2 / 62 (3.23%)	3 / 64 (4.69%)	0 / 62 (0.00%)	4 / 62 (6.45%)	1 / 62 (1.61%)
occurrences all number	3	6	0	4	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

07 May 2015

Protocol Version 2 The changes are summarized as follows: • Inclusion criterion 1 was updated to take into account differences in the definition of adult age between countries and regions. • Exclusion criterion 1 was updated to clarify which assessment result (screening) was to be considered for eligibility. • Wording regarding the terms background and rescue medication was changed to clarify that these referred to the standard of care medication as per local practice or a change of this medication. • A discontinuation criterion was updated to clarify that discontinuation of study drug administration was to be considered in cases where subjects experienced renal or CNS flare. • The schedule of assessments was updated to clarify that CLASI and exploratory biomarkers were also to be assessed at the time of early termination. • The assessment of ESR was removed from the protocol for the following reasons: 1) This was not an essential parameter needed for the planned analysis, 2) Other parameters (CRP, fibrinogen) that reflected the inflammation status of the subject were measured, and 3) Unblinding of the treatment when ESR was locally assessed and reported by study staff could be avoided. • For pregnancy testing, it was clarified that if local regulations required more frequent pregnancy testing, this was to be applied. • The wording on laboratory re-tests was updated to differentiate between re-test at screening and re-tests during the study. • The statement “SUSARs that are already present in the European Medicines Agency EudraVigilance database do not have to be once again reported to the Competent Authority because they have direct access to the EudraVigilance database” was deleted, as it only applied in European countries and this study was also conducted in non-EU countries. • The text in the section regarding follow-up of AEs was updated to clarify that all AEs were to be followed until satisfactory outcome.

03 May 2016

Protocol Version 3 The main changes are summarized as follows: • Inclusion criterion 2 was clarified to reflect that the diagnosis of SLE should have occurred at least 6 months prior to screening and that at screening the ACR and/or SLICC criteria needed to be fulfilled. • The dose of the allowed medication mycophenolate mofetil was updated from a maximum of 1.5 g/d to 2.0 g/d to allow the inclusion of subjects who were receiving the usual dose for SLE patients. The units of MTX and cyclosporine dosing regimens were corrected or further specified. • Wording was updated to specify that exclusion criterion 1: an A score on the revised BILAG-2004, not only applied to the screening assessment but also at baseline for the organ systems that could have been clinically assessed at that time point. Exclusion criterion 3 was updated to clarify that subjects with clinically non-significant infections could have been enrolled in the study, and exclusion criterion 7 was updated for clarification purposes. • The description of the analysis of the primary efficacy endpoint was expanded to specify that only subjects who discontinued before Week 24 were to be treated as non-responders for this endpoint at this time point. • Wording was added to clarify that after Week 24, the dose of NSAIDs could have been adjusted based on the Investigator’s discretion. • Wording was added to clarify that the Investigator may decide to interrupt study drug treatment for 1 dose according to his/her medical judgment because of an AE. • The laboratory parameter CPK was added to the list of biochemistry parameters being analyzed, and creatinine was added to the list of urinalysis parameters. Wording was added to accurately reflect what was to be tested when screening for hepatitis and to clarify that additional pregnancy testing could have been done. Clarifications were added to statements regarding the follow-up of unexplained or unexpected clinical laboratory tests.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase II Multicenter, Randomized, Double-blind, Placebo controlled, Dose-range Finding Study to Evaluate the Safety and Efficacy of ALX-0061 Administered Subcutaneously in Subjects with Moderate to Severe Active Systemic Lupus Erythematosus

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 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

Primary: 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

Secondary: Proportion of subjects with mBICLA response at Week 24 and Week 48

Secondary: Proportion of subjects with mBICLA response at Week 24 and Week 48

Secondary: Proportion of subjects with modified Systemic Lupus Erythematosus Responder Index (mSRI-4) response at Week 24 and Week 48

Secondary: Proportion of subjects with modified Systemic Lupus Erythematosus Responder Index (mSRI-4) response at Week 24 and Week 48

Secondary: Proportion of subjects with mSRI-5 response at Week 24 and Week 48

Secondary: Proportion of subjects with mSRI-5 response at Week 24 and Week 48

Secondary: Proportion of subjects with mSRI-6 response at Week 24 and Week 48

Secondary: Proportion of subjects with mSRI-6 response at Week 24 and Week 48

Secondary: Proportion of subjects with mSRI-7 response at Week 24 and Week 48

Secondary: Proportion of subjects with mSRI-7 response at Week 24 and Week 48

Secondary: Proportion of subjects with mSRI-8 response at Week 24 and Week 48

Secondary: Proportion of subjects with mSRI-8 response at Week 24 and Week 48

Secondary: Change from baseline in modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) score at Week 24 and Week 48

Secondary: Change from baseline in modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) score at Week 24 and Week 48

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement at Week 24 and Week 48

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement at Week 24 and Week 48

Secondary: Proportion of subjects with BILAG-2004 Enhanced Improvement at Week 24 and Week 48

Secondary: Proportion of subjects with BILAG-2004 Enhanced Improvement at Week 24 and Week 48

Secondary: BILAG-2004 Total Score at Baseline, Week 24 and Week 48

Secondary: BILAG-2004 Total Score at Baseline, Week 24 and Week 48

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement in mucocutaneous system at Week 24 and Week 48

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement in mucocutaneous system at Week 24 and Week 48

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement in musculoskeletal system at Week 24 and Week 48

Secondary: Proportion of subjects with BILAG-2004 Normal Improvement in musculoskeletal system at Week 24 and Week 48

Secondary: Proportion of subjects with persistent minimal or no activity in 9 organ systems according to BILAG-2004 Systems Tally at Week 24 and Week 48

Secondary: Proportion of subjects with persistent minimal or no activity in 9 organ systems according to BILAG-2004 Systems Tally at Week 24 and Week 48

Secondary: Change from baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48

Secondary: Change from baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48

Secondary: Change from baseline in Patient's Global Assessment at Week 24 and Week 48

Secondary: Change from baseline in Patient's Global Assessment at Week 24 and Week 48

Secondary: Change from baseline in proteinuria at Week 24 and Week 48

Secondary: Change from baseline in proteinuria at Week 24 and Week 48

Secondary: Number of subjects who were treatment-emergent urine sediment positive at Week 24 and Week 48

Secondary: Number of subjects who were treatment-emergent urine sediment positive at Week 24 and Week 48

Secondary: Change from baseline in serum creatinine at Week 24 and Week 48

Secondary: Change from baseline in serum creatinine at Week 24 and Week 48

Secondary: Change from baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48

Secondary: Change from baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48

Secondary: Percentage treatment failures from Baseline to Week 24 and Week 48

Secondary: Percentage treatment failures from Baseline to Week 24 and Week 48

Secondary: Proportion of subjects experiencing severe flares according to BILAG-2004 Flare Index from Baseline to Week 24 and Week 48

Secondary: Proportion of subjects experiencing severe flares according to BILAG-2004 Flare Index from Baseline to Week 24 and Week 48

Secondary: Proportion of subjects experiencing severe flares according to mSLEDAI-2K Flare Index (mSFI) from Baseline to Week 24 and Week 48

Secondary: Proportion of subjects experiencing severe flares according to mSLEDAI-2K Flare Index (mSFI) from Baseline to Week 24 and Week 48

Secondary: Percent change from baseline in daily dose of steroids at Week 24 and Week 48

Secondary: Percent change from baseline in daily dose of steroids at Week 24 and Week 48

Secondary: Proportion of subjects whose daily dose of steroids was reduced without severe flares during Weeks 40-48

Secondary: Proportion of subjects whose daily dose of steroids was reduced without severe flares during Weeks 40-48

Secondary: Proportion of subjects who discontinued Prednisone (or equivalent) by Week 48 without experiencing a severe flare

Secondary: Proportion of subjects who discontinued Prednisone (or equivalent) by Week 48 without experiencing a severe flare

Secondary: Change from baseline in physical component scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48

Secondary: Change from baseline in physical component scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48

Secondary: Change from baseline in mental component scores of SF-36 at Week 24 and Week 48

Secondary: Change from baseline in mental component scores of SF-36 at Week 24 and Week 48

Secondary: Change from baseline in 28 joint count swollenness (SJC28) score at Week 24 and Week 48

Secondary: Change from baseline in 28 joint count swollenness (SJC28) score at Week 24 and Week 48

Secondary: Change from baseline in 28 joint count tenderness (TJC28) score at Week 24 and Week 48

Secondary: Change from baseline in 28 joint count tenderness (TJC28) score at Week 24 and Week 48

Secondary: Change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48

Secondary: Change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48

Secondary: Change from baseline in CLASI Damage Score at Week 12, Week 24 and Week 48

Secondary: Change from baseline in CLASI Damage Score at Week 12, Week 24 and Week 48

Secondary: ALX-0061 Serum Concentrations at Week 24 and Week 48

Secondary: ALX-0061 Serum Concentrations at Week 24 and Week 48

Secondary: Actual values of soluble Interleukin 6 Receptor (sIL-6R) concentrations at Baseline, Week 24, and Week 48

Secondary: Actual values of soluble Interleukin 6 Receptor (sIL-6R) concentrations at Baseline, Week 24, and Week 48

Secondary: Actual values of C-reactive protein (CRP) concentrations at Baseline, Week 24, and Week 48

Secondary: Actual values of C-reactive protein (CRP) concentrations at Baseline, Week 24, and Week 48

Clinical Trial Results:
A Phase II Multicenter, Randomized, Double-blind, Placebo controlled, Dose-range Finding Study to Evaluate the Safety and Efficacy of ALX-0061 Administered Subcutaneously in Subjects with Moderate to Severe Active Systemic Lupus Erythematosus