Trial Outcomes & Findings for A Phase II Study to Evaluate Safety and Efficacy of ALX-0061 in Subjects With Systemic Lupus Erythematosus (NCT NCT02437890)
NCT ID: NCT02437890
Last Updated: 2019-02-26
Results Overview
The primary endpoint was evaluated by determining if there was a dose-response relationship between the mBICLA response rate at Week 24 and the dose administered, using the Multiple Comparison Procedure - Modelling (MCP-Mod) methodology. The existence of several candidate parametric models was assumed and multiple comparison techniques were used to choose the model(s) most likely to represent the true underlying dose-response curve. The selected model could further be used to guide the choice of adequate doses. mBICLA responders were defined as subjects who met all of the following criteria: 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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
312 participants
Primary outcome timeframe
At Week 24 visit
Results posted on
2019-02-26
Participant Flow
A total of 312 subjects were randomized at 91 sites located in Europe (37 sites; 155 subjects), Asia-Pacific (19 sites, 53 subjects), North America (21 sites; 52 subjects), and Latin America (14 sites, 52 subjects). Consent was obtained from the first subject on 02 July 2015; the last subject completed the final visit on 25 January 2018.
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.
Participant milestones
| Measure |
Placebo
Two s.c. injections with placebo every 2 weeks (q2w).
\*\*\*
Placebo was supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to the placebo group received 2 s.c. injections q2w:
Syringe A with placebo (1 mL) q2w starting at Day 1, up to and including Week 46.
Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.
|
ALX-0061 75 mg q4w
ALX-0061 75 mg every 4 weeks (q4w).
\*\*\*
Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 75 mg q4w received 2 s.c. injections q2w:
Syringe A with placebo (1 mL) q2w starting at Day 1, up to and including Week 46.
Syringe B with ALX-0061 (0.5 mL) q4w at Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44, and syringe B with placebo (0.5 mL) q4w at Weeks 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46.
|
ALX-0061 150 mg q4w
ALX-0061 150 mg every 4 weeks (q4w).
\*\*\*
Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 150 mg q4w received 2 s.c. injections q2w:
Syringe A with ALX-0061 (1 mL) q4w at Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44, and syringe A with placebo (1 mL) q4w at Weeks 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46.
Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.
|
ALX-0061 150 mg q2w
ALX-0061 150 mg every 2 weeks (q2w).
\*\*\*
Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 150 mg q2w received 2 s.c. injections q2w:
Syringe A with ALX-0061 (1 mL) q2w starting at Day 1, up to and including Week 46.
Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.
|
ALX-0061 225 mg q2w
ALX-0061 225 mg every 2 weeks (q2w).
\*\*\*
Vobarilizumab (ALX-0061) was supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 225 mg q2w received 2 s.c. injections q2w:
Syringe A with ALX-0061 (1 mL) q2w starting at Day 1, up to and including Week 46.
Syringe B with ALX-0061 (0.5 mL) q2w starting at Day 1, up to and including Week 46.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
62
|
64
|
62
|
62
|
62
|
|
Overall Study
COMPLETED
|
54
|
48
|
47
|
40
|
46
|
|
Overall Study
NOT COMPLETED
|
8
|
16
|
15
|
22
|
16
|
Reasons for withdrawal
| Measure |
Placebo
Two s.c. injections with placebo every 2 weeks (q2w).
\*\*\*
Placebo was supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to the placebo group received 2 s.c. injections q2w:
Syringe A with placebo (1 mL) q2w starting at Day 1, up to and including Week 46.
Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.
|
ALX-0061 75 mg q4w
ALX-0061 75 mg every 4 weeks (q4w).
\*\*\*
Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 75 mg q4w received 2 s.c. injections q2w:
Syringe A with placebo (1 mL) q2w starting at Day 1, up to and including Week 46.
Syringe B with ALX-0061 (0.5 mL) q4w at Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44, and syringe B with placebo (0.5 mL) q4w at Weeks 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46.
|
ALX-0061 150 mg q4w
ALX-0061 150 mg every 4 weeks (q4w).
\*\*\*
Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 150 mg q4w received 2 s.c. injections q2w:
Syringe A with ALX-0061 (1 mL) q4w at Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44, and syringe A with placebo (1 mL) q4w at Weeks 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46.
Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.
|
ALX-0061 150 mg q2w
ALX-0061 150 mg every 2 weeks (q2w).
\*\*\*
Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 150 mg q2w received 2 s.c. injections q2w:
Syringe A with ALX-0061 (1 mL) q2w starting at Day 1, up to and including Week 46.
Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46.
|
ALX-0061 225 mg q2w
ALX-0061 225 mg every 2 weeks (q2w).
\*\*\*
Vobarilizumab (ALX-0061) was supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 225 mg q2w received 2 s.c. injections q2w:
Syringe A with ALX-0061 (1 mL) q2w starting at Day 1, up to and including Week 46.
Syringe B with ALX-0061 (0.5 mL) q2w starting at Day 1, up to and including Week 46.
|
|---|---|---|---|---|---|
|
Overall Study
Non-compliance to study drug
|
0
|
1
|
0
|
0
|
1
|
|
Overall Study
Sponsor's decision
|
1
|
1
|
4
|
0
|
2
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Unable to attend visit(s)
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
3
|
0
|
3
|
1
|
|
Overall Study
Adverse Event
|
4
|
9
|
5
|
11
|
7
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
6
|
5
|
5
|
|
Overall Study
Death
|
0
|
0
|
0
|
2
|
0
|
Baseline Characteristics
A Phase II Study to Evaluate Safety and Efficacy of ALX-0061 in Subjects With Systemic Lupus Erythematosus
Baseline characteristics by cohort
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every two weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every two weeks (q2w)
|
Total
n=312 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
62 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
62 Participants
n=4 Participants
|
62 Participants
n=21 Participants
|
312 Participants
n=10 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Age, Continuous
|
42.3 years
STANDARD_DEVIATION 10.11 • n=5 Participants
|
42.0 years
STANDARD_DEVIATION 11.00 • n=7 Participants
|
41.8 years
STANDARD_DEVIATION 10.79 • n=5 Participants
|
39.2 years
STANDARD_DEVIATION 11.58 • n=4 Participants
|
42.0 years
STANDARD_DEVIATION 10.44 • n=21 Participants
|
41.4 years
STANDARD_DEVIATION 10.79 • n=10 Participants
|
|
Sex: Female, Male
Female
|
60 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
57 Participants
n=21 Participants
|
300 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
12 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
66 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
49 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
49 Participants
n=21 Participants
|
246 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Region of Enrollment
Argentina
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
4 participants
n=21 Participants
|
18 participants
n=10 Participants
|
|
Region of Enrollment
Hungary
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=4 Participants
|
4 participants
n=21 Participants
|
14 participants
n=10 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
11 participants
n=7 Participants
|
10 participants
n=5 Participants
|
11 participants
n=4 Participants
|
10 participants
n=21 Participants
|
52 participants
n=10 Participants
|
|
Region of Enrollment
Czechia
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
3 participants
n=21 Participants
|
6 participants
n=10 Participants
|
|
Region of Enrollment
Philippines
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
3 participants
n=4 Participants
|
2 participants
n=21 Participants
|
13 participants
n=10 Participants
|
|
Region of Enrollment
Ukraine
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
7 participants
n=5 Participants
|
8 participants
n=4 Participants
|
7 participants
n=21 Participants
|
33 participants
n=10 Participants
|
|
Region of Enrollment
Portugal
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
6 participants
n=10 Participants
|
|
Region of Enrollment
Russia
|
3 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
8 participants
n=4 Participants
|
6 participants
n=21 Participants
|
28 participants
n=10 Participants
|
|
Region of Enrollment
Spain
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
0 participants
n=21 Participants
|
8 participants
n=10 Participants
|
|
Region of Enrollment
South Korea
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
1 participants
n=21 Participants
|
5 participants
n=10 Participants
|
|
Region of Enrollment
Taiwan
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
7 participants
n=10 Participants
|
|
Region of Enrollment
Poland
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
3 participants
n=5 Participants
|
6 participants
n=4 Participants
|
5 participants
n=21 Participants
|
23 participants
n=10 Participants
|
|
Region of Enrollment
Mexico
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
5 participants
n=4 Participants
|
5 participants
n=21 Participants
|
26 participants
n=10 Participants
|
|
Region of Enrollment
Chile
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
2 participants
n=10 Participants
|
|
Region of Enrollment
Serbia
|
14 participants
n=5 Participants
|
11 participants
n=7 Participants
|
17 participants
n=5 Participants
|
11 participants
n=4 Participants
|
10 participants
n=21 Participants
|
63 participants
n=10 Participants
|
|
Region of Enrollment
Peru
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
6 participants
n=10 Participants
|
|
Region of Enrollment
Germany
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
2 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: At Week 24 visitPopulation: mITT Population - Non-response imputation (NRI)
The primary endpoint was evaluated by determining if there was a dose-response relationship between the mBICLA response rate at Week 24 and the dose administered, using the Multiple Comparison Procedure - Modelling (MCP-Mod) methodology. The existence of several candidate parametric models was assumed and multiple comparison techniques were used to choose the model(s) most likely to represent the true underlying dose-response curve. The selected model could further be used to guide the choice of adequate doses. mBICLA responders were defined as subjects who met all of the following criteria: 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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects Who Achieved a Response at Week 24 According to the Modified British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (mBICLA) Score
|
29 Participants
|
28 Participants
|
24 Participants
|
24 Participants
|
23 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
Number and percentage of mBICLA responders at Week 24 and Week 48
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With mBICLA Response at Week 24 and Week 48
Week 24
|
28 Participants
|
28 Participants
|
22 Participants
|
24 Participants
|
22 Participants
|
|
Number and Percentage of Subjects With mBICLA Response at Week 24 and Week 48
Week 48
|
28 Participants
|
32 Participants
|
22 Participants
|
19 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The composite index mSRI-4 enables quantification of decrease and increase in disease activity in a broad spectrum of manifestations thereby offering a comprehensive assessment of SLE disease status. mSRI combines advantages from 3 validated measurement tools. The mSRI-4 criteria for response are: 1. modified SLE disease activity index 2000 (mSLEDAI-2K): ≥ 4 point reduction (covers global disease improvement), 2. British Isles Lupus Assessment Group 2004 (BILAG-2004): no new A domain score and no more than 1 new increase to B (covers organ-specific disease improvement), 3. Physician's Global Assessment (PGA) (is used as validity and safety net for items that were not addressed by the other two indices): \< 10% increase from Baseline (no worsening) When all 3 criteria are met, the subject is a mSRI-4 responder at that time point. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With Modified Systemic Lupus Erythematosus Responder Index (mSRI-4) Response at Week 24 and Week 48
Week 24
|
37 Participants
|
39 Participants
|
30 Participants
|
33 Participants
|
29 Participants
|
|
Number and Percentage of Subjects With Modified Systemic Lupus Erythematosus Responder Index (mSRI-4) Response at Week 24 and Week 48
Week 48
|
34 Participants
|
36 Participants
|
29 Participants
|
26 Participants
|
33 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The mSRI-5 criteria for response are: 1. mSLEDAI-2K: ≥ 5 point reduction 2. BILAG-2004: no new A domain score and no more than 1 new increase to B domain score 3. PGA: no worsening (\< 10% increase from Baseline) Only subjects with Baseline mSLEDAI-2K ≥ 5 were considered for the derivation of that endpoint. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With mSRI-5 Response at Week 24 and Week 48
Week 24
|
17 Participants
|
24 Participants
|
19 Participants
|
20 Participants
|
16 Participants
|
|
Number and Percentage of Subjects With mSRI-5 Response at Week 24 and Week 48
Week 48
|
20 Participants
|
28 Participants
|
18 Participants
|
16 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The mSRI-6 criteria for response are: 1. mSLEDAI-2K: ≥ 6 point reduction 2. BILAG-2004: no new A domain score and no more than 1 new increase to B domain score 3. PGA: no worsening (\< 10% increase from Baseline) Only subjects with Baseline mSLEDAI-2K ≥ 6 were considered for the derivation of that endpoint. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With mSRI-6 Response at Week 24 and Week 48
Week 24
|
16 Participants
|
23 Participants
|
19 Participants
|
19 Participants
|
15 Participants
|
|
Number and Percentage of Subjects With mSRI-6 Response at Week 24 and Week 48
Week 48
|
20 Participants
|
28 Participants
|
16 Participants
|
16 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The mSRI-7 criteria for response are: 1. mSLEDAI-2K: ≥ 7 point reduction 2. BILAG-2004: no new A domain score and no more than 1 new increase to B domain score 3. PGA: no worsening (\< 10% increase from Baseline) Only subjects with Baseline mSLEDAI-2K ≥ 7 were considered for the derivation of that endpoint. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With mSRI-7 Response at Week 24 and Week 48
Week 24
|
9 Participants
|
8 Participants
|
8 Participants
|
12 Participants
|
7 Participants
|
|
Number and Percentage of Subjects With mSRI-7 Response at Week 24 and Week 48
Week 48
|
12 Participants
|
14 Participants
|
7 Participants
|
8 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The mSRI-8 criteria for response are: 1. mSLEDAI-2K: ≥ 8 point reduction 2. BILAG-2004: no new A domain score and no more than 1 new increase to B domain score 3. PGA: no worsening (\< 10% increase from Baseline) Only subjects with Baseline mSLEDAI-2K ≥ 8 were considered for the derivation of that endpoint. Subjects who were treatment failures or discontinued from treatment were considered non-responder after treatment failure/discontinuation.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With mSRI-8 Response at Week 24 and Week 48.
Week 24
|
9 Participants
|
7 Participants
|
8 Participants
|
10 Participants
|
7 Participants
|
|
Number and Percentage of Subjects With mSRI-8 Response at Week 24 and Week 48.
Week 48
|
11 Participants
|
14 Participants
|
7 Participants
|
7 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The Systemic Lupus Erythematosus Disease Activity Index 2000 is a 1-page weighted score for 24 items (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, etc). The manifestations felt to be most commonly contributing to disease activity are included and scored based on the presence (= 1 multiplied by weight) or absence (= 0) within 30 days prior to the evaluation. The total score ranges from 0-105 (= sum of individual scores), with 105 being higher disease activity. mSLEDAI-2K derives from the standard index by omitting low complement. Mean changes from baseline were derived from an ANCOVA model with treatment as factor and baseline mSLEDAI-2K Score and geographic region as covariates. A negative change from baseline reflects an improvement.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) Score at Week 24 and Week 48
Week 24
|
-4.0 score
Standard Error 0.42
|
-4.6 score
Standard Error 0.43
|
-3.8 score
Standard Error 0.43
|
-4.3 score
Standard Error 0.44
|
-3.6 score
Standard Error 0.44
|
|
Change From Baseline in Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) Score at Week 24 and Week 48
Week 48
|
-4.5 score
Standard Error 0.40
|
-5.2 score
Standard Error 0.43
|
-4.3 score
Standard Error 0.42
|
-4.9 score
Standard Error 0.48
|
-4.9 score
Standard Error 0.44
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With BILAG-2004 Normal Improvement at Week 24 and Week 48
Week 24
|
31 Participants
|
29 Participants
|
28 Participants
|
25 Participants
|
24 Participants
|
|
Number and Percentage of Subjects With BILAG-2004 Normal Improvement at Week 24 and Week 48
Week 48
|
34 Participants
|
34 Participants
|
29 Participants
|
22 Participants
|
25 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With BILAG-2004 Enhanced Improvement at Week 24 and Week 48
Week 24
|
7 Participants
|
16 Participants
|
11 Participants
|
6 Participants
|
13 Participants
|
|
Number and Percentage of Subjects With BILAG-2004 Enhanced Improvement at Week 24 and Week 48
Week 48
|
5 Participants
|
10 Participants
|
7 Participants
|
6 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: At Baseline, Week 24 and Week 48Population: mITT Population
The British Isles Lupus Assessment Group 2004 (BILAG-2004) is a comprehensive composite clinical index that has been developed based on the principle of a physician's intention to treat using a nominal consensus approach. In the index, the nine systems (not organs) considered are: constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, renal, ophthalmic and hematological. Disease activity in each of the nine systems is categorized into five levels: grades A (= severe disease activity requiring systemic high dose oral corticosteroids, i.v. pulse corticosteroids, etc.) to E (= system never involved). BILAG total score is derived by assigning the following value to each grade and summing the sores over all organ systems: A = 12, B = 8, C = 1, D/E = 0. The total score ranges from 0-108, with 108 representing high disease activity in all 9 systems requiring high doses of corticosteroids, starting/increasing immunosuppressive drugs, etc.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
BILAG-2004 Total Score at Baseline, Week 24 and Week 48
Baseline
|
17.4 score
Standard Error 0.78
|
17.9 score
Standard Error 0.69
|
15.2 score
Standard Error 0.68
|
17.4 score
Standard Error 0.71
|
17.3 score
Standard Error 0.82
|
|
BILAG-2004 Total Score at Baseline, Week 24 and Week 48
Week 24
|
6.8 score
Standard Error 0.78
|
5.7 score
Standard Error 0.79
|
7.0 score
Standard Error 0.76
|
7.2 score
Standard Error 0.94
|
7.4 score
Standard Error 0.84
|
|
BILAG-2004 Total Score at Baseline, Week 24 and Week 48
Week 48
|
6.0 score
Standard Error 0.73
|
4.0 score
Standard Error 0.72
|
5.2 score
Standard Error 0.74
|
6.0 score
Standard Error 0.92
|
6.2 score
Standard Error 0.91
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Mucocutaneous System at Week 24 and Week 48
Week 24
|
25 Participants
|
24 Participants
|
18 Participants
|
21 Participants
|
25 Participants
|
|
Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Mucocutaneous System at Week 24 and Week 48
Week 48
|
26 Participants
|
27 Participants
|
18 Participants
|
18 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Musculoskeletal System at Week 24 and Week 48
Week 24
|
41 Participants
|
39 Participants
|
36 Participants
|
36 Participants
|
33 Participants
|
|
Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Musculoskeletal System at Week 24 and Week 48
Week 48
|
40 Participants
|
38 Participants
|
35 Participants
|
33 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects With Persistent Minimal or no Activity in 9 Organ Systems According to BILAG-2004 Systems Tally at Week 24 and Week 48
Week 48
|
20 Participants
|
27 Participants
|
23 Participants
|
16 Participants
|
19 Participants
|
|
Number and Percentage of Subjects With Persistent Minimal or no Activity in 9 Organ Systems According to BILAG-2004 Systems Tally at Week 24 and Week 48
Week 24
|
15 Participants
|
24 Participants
|
19 Participants
|
16 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The physician makes a mark between 0 ("no disease") and 100 mm ("severe disease") on the visual analogue scale (VAS) to indicate disease activity (independent of the subject's self-assessment). Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline PGA score and geographic region as covariates. A negative change from baseline reflects an improvement.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48
Week 24
|
-25.2 score on a scale
Standard Error 2.03
|
-28.4 score on a scale
Standard Error 2.09
|
-26.2 score on a scale
Standard Error 2.04
|
-23.5 score on a scale
Standard Error 2.16
|
-22.7 score on a scale
Standard Error 2.08
|
|
Change From Baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48
Week 48
|
-28.3 score on a scale
Standard Error 1.73
|
-32.9 score on a scale
Standard Error 1.82
|
-30.2 score on a scale
Standard Error 1.82
|
-30.1 score on a scale
Standard Error 2.00
|
-30.5 score on a scale
Standard Error 1.87
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The subject makes a mark between 0 ("very good") and 100 mm ("very bad") on the VAS to indicate how the subject is doing, while considering all the ways SLE affects him/her. Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline Patient's Global Assessment and geographic region as covariates. A negative change from baseline reflects an improvement.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Patient's Global Assessment at Week 24 and Week 48
Week 24
|
-12.4 score on a scale
Standard Error 2.87
|
-13.5 score on a scale
Standard Error 2.96
|
-14.9 score on a scale
Standard Error 2.87
|
-20.1 score on a scale
Standard Error 3.05
|
-16.0 score on a scale
Standard Error 2.98
|
|
Change From Baseline in Patient's Global Assessment at Week 24 and Week 48
Week 48
|
-15.1 score on a scale
Standard Error 2.70
|
-21.5 score on a scale
Standard Error 2.87
|
-22.1 score on a scale
Standard Error 2.82
|
-27.2 score on a scale
Standard Error 3.12
|
-25.9 score on a scale
Standard Error 2.94
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Proteinuria at Week 24 and Week 48
Week 24
|
6.17 g/mol
Standard Error 3.730
|
1.77 g/mol
Standard Error 3.847
|
1.03 g/mol
Standard Error 3.735
|
-3.02 g/mol
Standard Error 3.876
|
0.16 g/mol
Standard Error 3.962
|
|
Change From Baseline in Proteinuria at Week 24 and Week 48
Week 48
|
4.89 g/mol
Standard Error 5.732
|
3.83 g/mol
Standard Error 6.152
|
-1.62 g/mol
Standard Error 5.761
|
-0.49 g/mol
Standard Error 6.582
|
-1.21 g/mol
Standard Error 6.191
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number of Subjects Who Were Treatment-emergent Urine Sediment Positive at Week 24 and Week 48
Week 24
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Subjects Who Were Treatment-emergent Urine Sediment Positive at Week 24 and Week 48
Week 48
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Serum Creatinine at Week 24 and Week 48
Week 24
|
-1.25 umol/L
Standard Error 2.172
|
-3.29 umol/L
Standard Error 2.237
|
-1.50 umol/L
Standard Error 2.182
|
-3.98 umol/L
Standard Error 2.309
|
-0.86 umol/L
Standard Error 2.276
|
|
Change From Baseline in Serum Creatinine at Week 24 and Week 48
Week 48
|
1.19 umol/L
Standard Error 2.016
|
-1.87 umol/L
Standard Error 2.152
|
-6.26 umol/L
Standard Error 2.085
|
-4.04 umol/L
Standard Error 2.359
|
-1.24 umol/L
Standard Error 2.199
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48
Week 24
|
-1.63 mL/min/1.73m2
Standard Error 2.869
|
4.83 mL/min/1.73m2
Standard Error 2.931
|
-1.72 mL/min/1.73m2
Standard Error 2.854
|
-0.90 mL/min/1.73m2
Standard Error 3.044
|
-8.91 mL/min/1.73m2
Standard Error 3.014
|
|
Change From Baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48
Week 48
|
-6.00 mL/min/1.73m2
Standard Error 3.052
|
2.47 mL/min/1.73m2
Standard Error 3.231
|
4.66 mL/min/1.73m2
Standard Error 3.125
|
-1.47 mL/min/1.73m2
Standard Error 3.562
|
-8.08 mL/min/1.73m2
Standard Error 3.326
|
SECONDARY outcome
Timeframe: From Baseline to Week 24 and Week 48Population: mITT Population
Defined as non-protocol allowed increase in steroid dose, start i.v. or i.m. steroids, or start or increase of immunosuppressant
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number of and Percentage Treatment Failures From Baseline to Week 24 and Week 48
Baseline to Week 24
|
2 Participants
|
0 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
|
Number of and Percentage Treatment Failures From Baseline to Week 24 and Week 48
Baseline to Week 48
|
5 Participants
|
1 Participants
|
9 Participants
|
6 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: From Baseline to Week 24 and Week 48Population: mITT Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects Experiencing Severe Flares According to BILAG-2004 Flare Index From Baseline to Week 24 and Week 48
Baseline to Week 24
|
8 Participants
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
|
Number and Percentage of Subjects Experiencing Severe Flares According to BILAG-2004 Flare Index From Baseline to Week 24 and Week 48
Baseline to Week 48
|
8 Participants
|
6 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: From Baseline to Week 24 and Week 48Population: mITT Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects Experiencing Severe Flares According to mSLEDAI-2K Flare Index (mSFI) From Baseline to Week 24 and Week 48
Baseline to Week 24
|
1 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Number and Percentage of Subjects Experiencing Severe Flares According to mSLEDAI-2K Flare Index (mSFI) From Baseline to Week 24 and Week 48
Baseline to Week 48
|
4 Participants
|
0 Participants
|
4 Participants
|
4 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
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
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Daily Dose of Steroids at Week 24 and Week 48
Week 24
|
3.87 percentage
Standard Error 2.781
|
-0.80 percentage
Standard Error 2.922
|
0.25 percentage
Standard Error 2.689
|
-1.40 percentage
Standard Error 2.940
|
-3.46 percentage
Standard Error 2.831
|
|
Percent Change From Baseline in Daily Dose of Steroids at Week 24 and Week 48
Week 48
|
6.93 percentage
Standard Error 5.047
|
-3.22 percentage
Standard Error 5.397
|
-1.03 percentage
Standard Error 5.050
|
-2.32 percentage
Standard Error 5.758
|
-1.73 percentage
Standard Error 5.521
|
SECONDARY outcome
Timeframe: Between Week 40 and Week 48Population: mITT Population
Number and percentage of subjects whose prednisone equivalent dose was \>7.5 mg/day at baseline and reduced to ≤7.5 mg/day during Weeks 40-48 without experiencing a BILAG-2004-defined or mSFI-defined severe flare after the first prednisone equivalent dose decrease.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects Whose Daily Dose of Steroids Was Reduced Without Severe Flares During Weeks 40-48
BILAG-2004-defined Flare
|
3 Participants
|
2 Participants
|
5 Participants
|
1 Participants
|
3 Participants
|
|
Number and Percentage of Subjects Whose Daily Dose of Steroids Was Reduced Without Severe Flares During Weeks 40-48
mSFI-defined Flare
|
3 Participants
|
2 Participants
|
4 Participants
|
1 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Up to and including Week 48Population: mITT Population
Number and percentage of subjects who discontinued Prednisone (or equivalent) by Week 48 without experiencing a BILAG-2004-defined or mSFI-defined severe flare
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects Who Discontinued Prednisone (or Equivalent) by Week 48 Without Experiencing a Severe Flare
mSFI-defined Flare
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number and Percentage of Subjects Who Discontinued Prednisone (or Equivalent) by Week 48 Without Experiencing a Severe Flare
BILAG-2004-defined Flare
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline SF-36 Score and geographic region as covariates. A positive change denotes an improvement.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Physical Component Scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48
Week 24
|
4.71 score
Standard Error 1.241
|
4.56 score
Standard Error 1.286
|
6.77 score
Standard Error 1.242
|
4.67 score
Standard Error 1.321
|
5.01 score
Standard Error 1.292
|
|
Change From Baseline in Physical Component Scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48
Week 48
|
3.73 score
Standard Error 1.414
|
6.97 score
Standard Error 1.510
|
8.67 score
Standard Error 1.460
|
8.62 score
Standard Error 1.633
|
8.85 score
Standard Error 1.535
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline SF-36 Score and geographic region as covariates. A positive change denotes an improvement.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Mental Component Scores of SF-36 at Week 24 and Week 48
Week 24
|
0.08 score
Standard Error 0.703
|
-0.99 score
Standard Error 0.724
|
-0.56 score
Standard Error 0.703
|
0.45 score
Standard Error 0.749
|
-1.18 score
Standard Error 0.732
|
|
Change From Baseline in Mental Component Scores of SF-36 at Week 24 and Week 48
Week 48
|
1.50 score
Standard Error 0.716
|
-0.58 score
Standard Error 0.756
|
-0.07 score
Standard Error 0.737
|
-1.07 score
Standard Error 0.827
|
-2.02 score
Standard Error 0.777
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
Twenty-eight joints are assessed for swollenness (a score of 1 for a joint denotes a presence of swollenness). The sum is derived to create a total score (ranging from 0 to 28; where the highest score indicate all 28 joints are swollen). Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline SJC28 Score and geographic region as covariates. A negative change denotes an improvement.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in 28 Joint Count Swollenness (SJC28) Score at Week 24 and Week 48
Week 24
|
-4.8 score
Standard Error 0.31
|
-5.0 score
Standard Error 0.32
|
-4.9 score
Standard Error 0.31
|
-4.8 score
Standard Error 0.33
|
-4.5 score
Standard Error 0.32
|
|
Change From Baseline in 28 Joint Count Swollenness (SJC28) Score at Week 24 and Week 48
Week 48
|
-5.0 score
Standard Error 0.28
|
-5.4 score
Standard Error 0.30
|
-4.7 score
Standard Error 0.29
|
-5.1 score
Standard Error 0.32
|
-4.5 score
Standard Error 0.30
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: mITT Population
Twenty-eight joints are assessed for tenderness (a score of 1 for a joint denotes a presence of tenderness). The sum is derived to create a total score (ranging from 0 to 28; where the highest score indicate all 28 joints are tender). Mean changes from baseline were derived from an analysis of covariance (ANCOVA) model with treatment as factor and baseline TJC28 Score and geographic region as covariates. A negative change denotes and improvement.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in 28 Joint Count Tenderness (TJC28) Score at Week 24 and Week 48
Week 24
|
-6.8 score
Standard Error 0.49
|
-6.8 score
Standard Error 0.50
|
-6.4 score
Standard Error 0.49
|
-5.8 score
Standard Error 0.52
|
-5.5 score
Standard Error 0.50
|
|
Change From Baseline in 28 Joint Count Tenderness (TJC28) Score at Week 24 and Week 48
Week 48
|
-6.6 score
Standard Error 0.43
|
-7.4 score
Standard Error 0.46
|
-6.4 score
Standard Error 0.45
|
-6.6 score
Standard Error 0.50
|
-6.5 score
Standard Error 0.47
|
SECONDARY outcome
Timeframe: At Week 12, Week 24 and Week 48Population: mITT Population
CLASI Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and nonscarring alopecia. Evaluation of erythema and scale/hyperkeratosis is based on a table: rows represent anatomical areas and columns represent major clinical symptoms. The extent of involvement for each of the skin symptoms is documented for each anatomic area (erythema: 0=absent, 1=pink, 2=red, 3=dark red; scale: 0=absent, 1=scale, 2=verrucous/hypertrophic). Mucous membrane involvement and acute hair loss are scored based on the presence (=1) or absence (=0). Nonscarring alopecia is scored as 0=absent, 1=diffuse/non-inflammatory, 2=focal or patchy in 1 quadrant, 3=focal or patchy in \>1 quadrant. The total score ranges from 0-70, with higher scores indicating more severe skin disease. Mean changes from baseline were derived from an ANCOVA model with treatment as factor and baseline CLASI Activity Score and geographic region as covariates. Negative change = improvement
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48
Week 12
|
-2.4 score
Standard Error 0.53
|
-1.9 score
Standard Error 0.57
|
-1.4 score
Standard Error 0.65
|
-1.6 score
Standard Error 0.63
|
-1.3 score
Standard Error 0.57
|
|
Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48
Week 24
|
-1.1 score
Standard Error 0.53
|
-2.1 score
Standard Error 0.60
|
-1.6 score
Standard Error 0.66
|
-1.3 score
Standard Error 0.65
|
-1.8 score
Standard Error 0.57
|
|
Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48
Week 48
|
-1.3 score
Standard Error 0.59
|
-3.0 score
Standard Error 0.70
|
-2.5 score
Standard Error 0.73
|
-2.1 score
Standard Error 0.80
|
-3.0 score
Standard Error 0.64
|
SECONDARY outcome
Timeframe: At Week 12, Week 24 and Week 48Population: mITT Population
CLASI Damage is scored based on dyspigmentation and scarring. Evaluation of dyspigmentation and scarring is based on a table: rows represent anatomical areas and columns represent major clinical symptoms. The extent of involvement for each of the skin symptoms is documented for each anatomic area (dyspigmentation: 0=absent, 1=present; scarring: 0=absent, 1=scarring, 2=severely atrophic scarring or panniculitis). Subjects are also asked whether dyspigmentation due to SLE lesions usually remains visible for \>12 months, which is considered permanent and results in doubling of the dyspigmentation score. Scarring alopecia is scored as follows: 0=absent, 3=1 quadrant, 4=2 quadrants, 5=3 quadrants, 6=affects the whole skull. Total score ranges from 0-56, with higher scores indicating more damaged skin. Mean changes from baseline were derived from an ANCOVA model with treatment as factor and baseline CLASI Damage Score and geographic region as covariates. Negative change = improvement.
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Change From Baseline in CLASI Damage Score at Week 12, Week 24 and Week 48
Week 12
|
0.1 score
Standard Error 0.49
|
0.1 score
Standard Error 0.47
|
-0.1 score
Standard Error 0.59
|
-0.3 score
Standard Error 0.52
|
-0.4 score
Standard Error 0.52
|
|
Change From Baseline in CLASI Damage Score at Week 12, Week 24 and Week 48
Week 24
|
0.4 score
Standard Error 0.61
|
-0.4 score
Standard Error 0.61
|
-0.4 score
Standard Error 0.73
|
0.3 score
Standard Error 0.67
|
-0.1 score
Standard Error 0.66
|
|
Change From Baseline in CLASI Damage Score at Week 12, Week 24 and Week 48
Week 48
|
0.0 score
Standard Error 0.57
|
-0.1 score
Standard Error 0.60
|
-0.3 score
Standard Error 0.68
|
0.4 score
Standard Error 0.68
|
-0.7 score
Standard Error 0.63
|
SECONDARY outcome
Timeframe: At Week 24 and Week 48Population: Safety Population
Outcome measures
| Measure |
Placebo
n=64 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=62 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
ALX-0061 Serum Concentrations at Week 24 and Week 48
Week 24
|
0.118 µg/mL
Standard Deviation 2.29
|
2.05 µg/mL
Standard Deviation 3.89
|
18.1 µg/mL
Standard Deviation 1.60
|
30.7 µg/mL
Standard Deviation 1.62
|
—
|
|
ALX-0061 Serum Concentrations at Week 24 and Week 48
Week 48
|
0.155 µg/mL
Standard Deviation 3.28
|
2.17 µg/mL
Standard Deviation 3.45
|
17.9 µg/mL
Standard Deviation 1.71
|
36.1 µg/mL
Standard Deviation 1.46
|
—
|
SECONDARY outcome
Timeframe: At Baseline, Week 24, and Week 48Population: Safety Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Actual Values of Soluble Interleukin 6 Receptor (sIL-6R) Concentrations at Baseline, Week 24, and Week 48
Baseline
|
42.22 ng/mL
Standard Error 2.496
|
37.63 ng/mL
Standard Error 1.933
|
38.10 ng/mL
Standard Error 1.895
|
42.14 ng/mL
Standard Error 3.366
|
36.92 ng/mL
Standard Error 1.810
|
|
Actual Values of Soluble Interleukin 6 Receptor (sIL-6R) Concentrations at Baseline, Week 24, and Week 48
Week 24
|
39.70 ng/mL
Standard Error 1.934
|
198.26 ng/mL
Standard Error 18.856
|
603.51 ng/mL
Standard Error 31.678
|
668.57 ng/mL
Standard Error 25.568
|
634.49 ng/mL
Standard Error 23.638
|
|
Actual Values of Soluble Interleukin 6 Receptor (sIL-6R) Concentrations at Baseline, Week 24, and Week 48
Week 48
|
39.41 ng/mL
Standard Error 2.270
|
224.66 ng/mL
Standard Error 25.515
|
610.86 ng/mL
Standard Error 29.445
|
650.73 ng/mL
Standard Error 38.516
|
659.79 ng/mL
Standard Error 32.862
|
SECONDARY outcome
Timeframe: At Baseline, Week 24, and Week 48Population: Safety Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Actual Values of C-reactive Protein (CRP) Concentrations at Baseline, Week 24, and Week 48
Baseline
|
43.58 nmol/L
Standard Error 9.527
|
49.05 nmol/L
Standard Error 12.924
|
38.89 nmol/L
Standard Error 8.394
|
66.32 nmol/L
Standard Error 17.221
|
32.23 nmol/L
Standard Error 4.957
|
|
Actual Values of C-reactive Protein (CRP) Concentrations at Baseline, Week 24, and Week 48
Week 24
|
59.43 nmol/L
Standard Error 11.277
|
47.22 nmol/L
Standard Error 9.607
|
26.08 nmol/L
Standard Error 9.995
|
3.83 nmol/L
Standard Error 0.668
|
3.20 nmol/L
Standard Error 0.357
|
|
Actual Values of C-reactive Protein (CRP) Concentrations at Baseline, Week 24, and Week 48
Week 48
|
30.70 nmol/L
Standard Error 4.709
|
37.65 nmol/L
Standard Error 8.647
|
23.20 nmol/L
Standard Error 6.705
|
4.41 nmol/L
Standard Error 0.988
|
4.02 nmol/L
Standard Error 0.962
|
SECONDARY outcome
Timeframe: At Baseline, Week 24, and Week 48Population: Safety Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Actual Values of Fibrinogen Concentrations at Baseline, Week 24, and Week 48
Baseline
|
3.2 g/L
Standard Error 0.09
|
3.2 g/L
Standard Error 0.08
|
3.2 g/L
Standard Error 0.09
|
3.2 g/L
Standard Error 0.10
|
3.1 g/L
Standard Error 0.09
|
|
Actual Values of Fibrinogen Concentrations at Baseline, Week 24, and Week 48
Week 24
|
3.3 g/L
Standard Error 0.08
|
3.3 g/L
Standard Error 0.10
|
2.3 g/L
Standard Error 0.12
|
1.9 g/L
Standard Error 0.05
|
1.9 g/L
Standard Error 0.05
|
|
Actual Values of Fibrinogen Concentrations at Baseline, Week 24, and Week 48
Week 48
|
3.3 g/L
Standard Error 0.09
|
3.3 g/L
Standard Error 0.12
|
2.3 g/L
Standard Error 0.11
|
1.9 g/L
Standard Error 0.06
|
1.9 g/L
Standard Error 0.05
|
SECONDARY outcome
Timeframe: at Baseline, Week 24, and Week 48Population: Safety Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Actual Values of Anti-double-stranded (ds) DNA Concentrations at Baseline, Week 24, and Week 48
Baseline
|
132.90 IU/mL
Standard Error 54.467
|
145.87 IU/mL
Standard Error 113.907
|
52.88 IU/mL
Standard Error 17.283
|
68.92 IU/mL
Standard Error 23.226
|
73.34 IU/mL
Standard Error 25.940
|
|
Actual Values of Anti-double-stranded (ds) DNA Concentrations at Baseline, Week 24, and Week 48
Week 24
|
81.36 IU/mL
Standard Error 30.376
|
68.27 IU/mL
Standard Error 35.053
|
46.99 IU/mL
Standard Error 33.534
|
14.98 IU/mL
Standard Error 4.499
|
23.25 IU/mL
Standard Error 6.417
|
|
Actual Values of Anti-double-stranded (ds) DNA Concentrations at Baseline, Week 24, and Week 48
Week 48
|
81.80 IU/mL
Standard Error 24.143
|
59.48 IU/mL
Standard Error 32.190
|
74.21 IU/mL
Standard Error 48.030
|
9.13 IU/mL
Standard Error 2.108
|
15.53 IU/mL
Standard Error 6.069
|
SECONDARY outcome
Timeframe: At Baseline, Week 24, and Week 48Population: Safety Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Actual Values of Complement C3 Concentrations at Baseline, Week 24, and Week 48
Baseline
|
102.3 mg/dL
Standard Error 3.82
|
100.2 mg/dL
Standard Error 4.12
|
101.9 mg/dL
Standard Error 3.79
|
105.8 mg/dL
Standard Error 4.38
|
98.6 mg/dL
Standard Error 3.98
|
|
Actual Values of Complement C3 Concentrations at Baseline, Week 24, and Week 48
Week 24
|
101.7 mg/dL
Standard Error 4.30
|
95.7 mg/dL
Standard Error 3.81
|
82.0 mg/dL
Standard Error 3.68
|
75.3 mg/dL
Standard Error 2.90
|
71.8 mg/dL
Standard Error 2.82
|
|
Actual Values of Complement C3 Concentrations at Baseline, Week 24, and Week 48
Week 48
|
95.8 mg/dL
Standard Error 4.25
|
93.2 mg/dL
Standard Error 4.20
|
79.0 mg/dL
Standard Error 3.25
|
83.2 mg/dL
Standard Error 3.18
|
72.3 mg/dL
Standard Error 2.61
|
SECONDARY outcome
Timeframe: At Baseline, Week 24, and Week 48Population: Safety Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Actual Values of Complement C4 Concentrations at Baseline, Week 24, and Week 48
Baseline
|
17.3 mg/dL
Standard Error 1.08
|
17.8 mg/dL
Standard Error 1.07
|
15.9 mg/dL
Standard Error 0.96
|
18.7 mg/dL
Standard Error 1.19
|
16.3 mg/dL
Standard Error 1.04
|
|
Actual Values of Complement C4 Concentrations at Baseline, Week 24, and Week 48
Week 24
|
17.5 mg/dL
Standard Error 1.09
|
17.4 mg/dL
Standard Error 1.10
|
10.6 mg/dL
Standard Error 0.85
|
8.7 mg/dL
Standard Error 0.40
|
7.9 mg/dL
Standard Error 0.37
|
|
Actual Values of Complement C4 Concentrations at Baseline, Week 24, and Week 48
Week 48
|
16.3 mg/dL
Standard Error 1.15
|
17.3 mg/dL
Standard Error 1.27
|
10.5 mg/dL
Standard Error 0.84
|
9.8 mg/dL
Standard Error 0.89
|
8.1 mg/dL
Standard Error 0.41
|
SECONDARY outcome
Timeframe: At Baseline, Week 24, and Week 48Population: Safety Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Actual Values for Hemolytic Complement Component 50 (CH50) at Baseline, Week 24, and Week 48
Week 48
|
102.2 unit(s)
Standard Error 8.38
|
113.1 unit(s)
Standard Error 8.63
|
73.5 unit(s)
Standard Error 8.26
|
68.4 unit(s)
Standard Error 6.95
|
41.9 unit(s)
Standard Error 3.32
|
|
Actual Values for Hemolytic Complement Component 50 (CH50) at Baseline, Week 24, and Week 48
Baseline
|
101.1 unit(s)
Standard Error 7.46
|
109.6 unit(s)
Standard Error 8.83
|
98.9 unit(s)
Standard Error 6.95
|
103.0 unit(s)
Standard Error 7.47
|
82.4 unit(s)
Standard Error 7.09
|
|
Actual Values for Hemolytic Complement Component 50 (CH50) at Baseline, Week 24, and Week 48
Week 24
|
95.8 unit(s)
Standard Error 7.94
|
107.0 unit(s)
Standard Error 7.08
|
73.6 unit(s)
Standard Error 6.94
|
56.7 unit(s)
Standard Error 4.91
|
41.1 unit(s)
Standard Error 3.63
|
SECONDARY outcome
Timeframe: From first administration of ALX-0061 up to and including follow-upPopulation: Safety Population
Outcome measures
| Measure |
Placebo
n=62 Participants
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 Participants
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 Participants
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 Participants
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 Participants
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Number and Percentage of Subjects Who Were Treatment-emergent (TE) Anti-drug Antibody (ADA) Positive
|
32 Participants
|
16 Participants
|
18 Participants
|
31 Participants
|
38 Participants
|
Adverse Events
Placebo
Serious events: 7 serious events
Other events: 40 other events
Deaths: 0 deaths
ALX-0061 75 mg q4w
Serious events: 2 serious events
Other events: 40 other events
Deaths: 0 deaths
ALX-0061 150 mg q4w
Serious events: 4 serious events
Other events: 31 other events
Deaths: 0 deaths
ALX-0061 150 mg q2w
Serious events: 5 serious events
Other events: 47 other events
Deaths: 2 deaths
ALX-0061 225 mg q2w
Serious events: 5 serious events
Other events: 44 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=62 participants at risk
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 participants at risk
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 participants at risk
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 participants at risk
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 participants at risk
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Infections and infestations
Cellulitis
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.2%
2/62 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Pneumonia
|
3.2%
2/62 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Sinusitis
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Cytomegalovirus infection
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Erysipelas
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Meningitis
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/64 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Peritonsillar abscess
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Pulmonary tuberculoma
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Tuberculous pleurisy
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Blood and lymphatic system disorders
Anemia of chronic disease
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Gastrointestinal disorders
Gastric ulcer
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Gastrointestinal disorders
Pancreatitis chronic
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Nervous system disorders
Generalized tonic-clonic seizure
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/64 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Nervous system disorders
Hypoxic-ischemic encephalopathy
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Nervous system disorders
Seizure
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Psychiatric disorders
Depression
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Vascular disorders
Vasculitis
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Eye disorders
Open angle glaucoma
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
General disorders
Pyrexia
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Immune system disorders
Allergy to arthropod sting
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
Other adverse events
| Measure |
Placebo
n=62 participants at risk
Two s.c. injections with placebo every 2 weeks (q2w)
|
ALX-0061 75 mg q4w
n=64 participants at risk
ALX-0061 75 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q4w
n=62 participants at risk
ALX-0061 150 mg every 4 weeks (q4w)
|
ALX-0061 150 mg q2w
n=62 participants at risk
ALX-0061 150 mg every 2 weeks (q2w)
|
ALX-0061 225 mg q2w
n=62 participants at risk
ALX-0061 225 mg every 2 weeks (q2w)
|
|---|---|---|---|---|---|
|
Infections and infestations
Urinary tract infection
|
12.9%
8/62 • Number of events 11 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
7.8%
5/64 • Number of events 10 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
11.3%
7/62 • Number of events 10 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.8%
3/62 • Number of events 5 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
12.9%
8/62 • Number of events 12 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Upper respiratory tract infection
|
8.1%
5/62 • Number of events 5 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
7.8%
5/64 • Number of events 7 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
8.1%
5/62 • Number of events 5 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
8.1%
5/62 • Number of events 8 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.8%
3/62 • Number of events 5 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Nasopharyngitis
|
9.7%
6/62 • Number of events 8 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
9.4%
6/64 • Number of events 7 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
8.1%
5/62 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.2%
2/62 • Number of events 3 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Bronchitis
|
3.2%
2/62 • Number of events 3 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.1%
2/64 • Number of events 3 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
6.5%
4/62 • Number of events 4 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.2%
2/62 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Infections and infestations
Sinusitis
|
3.2%
2/62 • Number of events 3 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.7%
3/64 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
6.5%
4/62 • Number of events 4 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Gastrointestinal disorders
Diarrhoea
|
9.7%
6/62 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/64 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.2%
2/62 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Gastrointestinal disorders
Nausea
|
6.5%
4/62 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/64 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.2%
2/62 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.2%
2/62 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
General disorders
Injection site erythema
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.1%
2/64 • Number of events 3 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.2%
2/62 • Number of events 5 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
8.1%
5/62 • Number of events 17 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
8.1%
5/62 • Number of events 11 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
General disorders
Injection site rash
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.7%
3/64 • Number of events 3 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
6.5%
4/62 • Number of events 17 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.8%
3/62 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
General disorders
Injection site reaction
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
6.5%
4/62 • Number of events 5 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 5 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.5%
4/62 • Number of events 5 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.1%
2/64 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Nervous system disorders
Headache
|
21.0%
13/62 • Number of events 16 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
6.2%
4/64 • Number of events 27 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.8%
3/62 • Number of events 4 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.8%
3/62 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
16.1%
10/62 • Number of events 10 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/64 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
6.5%
4/62 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.2%
2/62 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.2%
2/62 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.7%
3/64 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.8%
3/62 • Number of events 3 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
8.1%
5/62 • Number of events 9 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
9.7%
6/62 • Number of events 7 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/64 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
9.7%
6/62 • Number of events 6 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
0.00%
0/62 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
|
Vascular disorders
Hypertension
|
6.5%
4/62 • Number of events 4 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
3.1%
2/64 • Number of events 2 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.8%
3/62 • Number of events 4 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
4.8%
3/62 • Number of events 3 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
1.6%
1/62 • Number of events 1 • From time of first study drug administration until the subject's study completion/discontinuation date.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Publication of any results from this study will be according to the principles of the Declaration of Helsinki, in particular point 30, and will require prior review and written agreement of the Sponsor.
- Publication restrictions are in place
Restriction type: OTHER