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A Phase IIb Study for ALX-0061 Monotherapy in Subjects With Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02287922
Recruitment Status : Completed
First Posted : November 11, 2014
Results First Posted : August 21, 2019
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
Ablynx

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Biological: ALX-0061
Biological: Placebo
Biological: Tocilizumab
Enrollment 251
Recruitment Details A total of 251 subjects were recruited at 58 sites located in Europe (42 sites; 199 subjects), Latin America (6 sites; 36 subjects) and North America (10 sites; 16 subjects). Consent was obtained from the first subject on 18 Mar 2015; the last subject completed the final visit in on 19 Jul 2016.
Pre-assignment Details Of the 599 subjects screened, 348 were screen failures and 251 subjects were randomly assigned to treatment (Intent-to-treat population). All subjects enrolled received study treatment and were included in the safety population. All subjects who received at least one dose of ALX-0061 were included in the pharmacokinetic (PK) population.
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label tocilizumab (TCZ). Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Period Title: Overall Study
Started 62 62 63 64
Completed 59 60 56 57
Not Completed 3 2 7 7
Reason Not Completed
Adverse Event             1             1             3             4
Withdrawal by Subject             1             1             1             2
Lost to Follow-up             0             0             1             0
Sponsor's decision             0             0             0             1
Other             1             0             2             0
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w Total
Hide Arm/Group Description

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Total of all reporting groups
Overall Number of Baseline Participants 62 62 63 64 251
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 62 participants 63 participants 64 participants 251 participants
<=18 years
0
   0.0%
1
   1.6%
0
   0.0%
0
   0.0%
1
   0.4%
Between 18 and 65 years
50
  80.6%
53
  85.5%
56
  88.9%
58
  90.6%
217
  86.5%
>=65 years
12
  19.4%
8
  12.9%
7
  11.1%
6
   9.4%
33
  13.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 62 participants 62 participants 63 participants 64 participants 251 participants
53.0  (12.25) 51.2  (12.05) 51.3  (11.81) 50.0  (12.26) 51.4  (12.07)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 62 participants 63 participants 64 participants 251 participants
Female
49
  79.0%
53
  85.5%
54
  85.7%
56
  87.5%
212
  84.5%
Male
13
  21.0%
9
  14.5%
9
  14.3%
8
  12.5%
39
  15.5%
1.Primary Outcome
Title Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12
Hide Description

ACR 20 response is defined as:

  • 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND
  • 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND
  • 20% improvement in 3 of the following 5 areas relative to Week 0:

    • Subject's Assessment of Pain (100 mm - visual analogue scale [VAS])
    • Subject's Global Assessment of Disease Activity (VASPA)
    • Physician's Global Assessment of Disease Activity (VASPHA)
    • Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI)
    • C-reactive protein (CRP) level

The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
45
  72.6%
48
  77.4%
51
  81.0%
50
  78.1%
2.Secondary Outcome
Title Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12
Hide Description

ACR50/70 response is defined as:

  • 50/70% improvement in TJC (68 joints) relative to Week 0 AND
  • 50/70% improvement in SJC (66 joints) relative to Week 0 AND
  • 50/70% improvement in 3 of the following 5 areas relative to Week 0:

    • Subject's Assessment of Pain (100 mm - VAS)
    • Subject's Global Assessment of Disease Activity (VASPA)
    • Physician's Global Assessment of Disease Activity (VASPHA)
    • Subject's assessment of physical function as measured by HAQ-DI
    • CRP level

This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 12 were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
ACR50
27
  43.5%
23
  37.1%
31
  49.2%
29
  45.3%
ACR70
10
  16.1%
15
  24.2%
13
  20.6%
15
  23.4%
3.Secondary Outcome
Title Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12
Hide Description

DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln[CRP+1]) + (0.014 × VASPA) + 0.96

Low disease activity = 2.6 ≤ DAS28 ≤ 3.2

Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
26
  41.9%
35
  56.5%
38
  60.3%
28
  43.8%
4.Secondary Outcome
Title Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12
Hide Description

DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln[ESR]) +(0.014 × VASPA)

Low disease activity = 2.6 ≤ DAS28 ≤ 3.2

Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
26
  41.9%
32
  51.6%
34
  54.0%
20
  31.3%
5.Secondary Outcome
Title Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12
Hide Description

SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL)

Low disease activity: 3.3 < SDAI ≤ 11.0

Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
23
  37.1%
27
  43.5%
33
  52.4%
22
  34.4%
6.Secondary Outcome
Title Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12
Hide Description

CDAI = TJC28 + SJC28 + VASPA + VASPHA

Low disease activity: 2.8 < CDAI ≤ 10

Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
23
  37.1%
21
  33.9%
32
  50.8%
21
  32.8%
7.Secondary Outcome
Title Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12
Hide Description

EULAR good response is defined as an improvement of >1.2 in DAS28 (CRP) relative to baseline.

This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
25
  40.3%
34
  54.8%
38
  60.3%
28
  43.8%
8.Secondary Outcome
Title Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12
Hide Description

DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln[ESR]) +(0.014 × VASPA)

Remission = DAS28(ESR) < 2.6

This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
21
  33.9%
13
  21.0%
25
  39.7%
16
  25.0%
9.Secondary Outcome
Title Number and Percentage of Subjects in Remission Using SDAI at Week 12
Hide Description

SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL)

Remission: SDAI ≤ 3.3

This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
5
   8.1%
3
   4.8%
5
   7.9%
7
  10.9%
10.Secondary Outcome
Title Number and Percentage of Subjects in Remission Using CDAI at Week 12
Hide Description

CDAI = TJC28 + SJC28 + VASPA + VASPHA

Remission: CDAI ≤ 2.8

This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
6
   9.7%
3
   4.8%
4
   6.3%
6
   9.4%
11.Secondary Outcome
Title Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12
Hide Description

Boolean remission: tender joint count (TJC)28 ≤ 1 and swollen joint count (SJC)28 ≤ 1 and VASPA (cm) ≤ 1 and CRP (mg/dL) ≤ 1

This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
2
   3.2%
3
   4.8%
4
   6.3%
4
   6.3%
12.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
Hide Description

The HAQ-DI is a 20-question instrument which assesses the degree of difficulty the subject had in accomplishing tasks in 8 functional areas over the previous week. The 8 areas are: dressing and grooming, hygiene, arising, reach, eating, grip, walking, common daily activities. Within each area, subjects report the amount of difficulty they have in performing the specific items. There are 4 response options ranging from: 0 = No Difficulty, 1 = With Some Difficulty, 2 = With Much Difficulty, 3 = Unable to Do. The 8 areas are each given a single score equal to the maximum value of their component activities (0, 1, 2, or 3). The sum of the area scores is then divided by the number of areas answered to obtain the final HAQ score (rounded to the nearest value evenly divisible by 0.125). The final HAQ-DI score ranges from 0 to 3. A high score means a high degree of disability (=worse outcome).

Missing values were imputed with the last non-missing observation.

Time Frame From baseline until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, number of participants with data available
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 61 60 59 64
Mean (Standard Error)
Unit of Measure: score on a scale
-0.541  (0.0809) -0.746  (0.0935) -0.817  (0.0802) -0.689  (0.0811)
13.Secondary Outcome
Title Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12
Hide Description The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. Low score indicates greater disability.
Time Frame From baseline until week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Mean (Standard Error)
Unit of Measure: score on a scale
physical component Number Analyzed 58 participants 60 participants 56 participants 54 participants
7.808  (0.8533) 7.979  (1.1895) 8.861  (1.0818) 7.611  (0.9562)
mental component Number Analyzed 58 participants 60 participants 56 participants 55 participants
5.49  (1.221) 8.836  (1.5243) 8.913  (1.3903) 6.156  (1.3192)
14.Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12
Hide Description The FACIT Measurement System is a collection of health-related quality of life questionnaires that assess multidimensional health status in people with various chronic illnesses. The FACIT Fatigue Scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue.
Time Frame From baseline until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, number of subjects with data available
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 58 60 56 57
Mean (Standard Error)
Unit of Measure: score on a scale
7.832  (1.3438) 11.41  (1.53) 12.996  (1.3702) 8.971  (1.4461)
15.Secondary Outcome
Title Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R)
Hide Description Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).
Time Frame From baseline until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Mean (Standard Error)
Unit of Measure: ng/mL
Baseline Number Analyzed 62 participants 62 participants 63 participants 64 participants
33.0  (4.65) 42.3  (8.71) 30.9  (3.72) 31.0  (2.54)
Week 12 Number Analyzed 58 participants 59 participants 56 participants 56 participants
376  (21.6) 460  (19.9) 459  (18.8) 269  (11.1)
16.Secondary Outcome
Title Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12
Hide Description [Not Specified]
Time Frame From baseline until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population, participants with data available
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Overall Number of Participants Analyzed 54 55 52
Geometric Mean (Standard Deviation)
Unit of Measure: micrograms/milliliter
1.4  (3.61) 18.4  (2.95) 27.9  (2.53)
17.Secondary Outcome
Title Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response
Hide Description [Not Specified]
Time Frame From first study drug intake up to and including follow-up (FU), i.e., maximum of 22 weeks (10 weeks of treatment + 12 weeks of FU)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w ALX-0061 Total
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

This group includes all participants who received at least one dose of ALX-0061
Overall Number of Participants Analyzed 62 62 63 187
Measure Type: Count of Participants
Unit of Measure: Participants
7
  11.3%
25
  40.3%
26
  41.3%
58
  31.0%
18.Secondary Outcome
Title Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity
Hide Description [Not Specified]
Time Frame From baseline until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
Mild
22
  35.5%
18
  29.0%
21
  33.3%
19
  29.7%
Moderate
12
  19.4%
13
  21.0%
9
  14.3%
10
  15.6%
Severe
0
   0.0%
2
   3.2%
1
   1.6%
2
   3.1%
19.Secondary Outcome
Title Number of Treatment-emergent Adverse Event by Severity
Hide Description [Not Specified]
Time Frame From baseline until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Number
Unit of Measure: Treatment-emergent adverse events
Mild 46 75 84 47
Moderate 18 22 15 15
Severe 0 2 3 2
20.Secondary Outcome
Title Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event
Hide Description treatment related = considered at least possibly related to study drug by the Investigator
Time Frame From baseline until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Count of Participants
Unit of Measure: Participants
21
  33.9%
20
  32.3%
21
  33.3%
20
  31.3%
21.Secondary Outcome
Title Number of Treatment-related Treatment-emergent Adverse Event
Hide Description treatment related = considered at least possibly related to study drug by the Investigator
Time Frame From baseline until Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description:

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

Overall Number of Participants Analyzed 62 62 63 64
Measure Type: Number
Unit of Measure: treatment-emergent adverse events
46 53 64 32
Time Frame From first study drug intake up to and including follow-up, i.e., maximum of 22 weeks when assigned to the ALX-0061 or TCZ q2w treatment groups (10 weeks of treatment + 12 weeks of follow-up), or 23 weeks when assigned to the TCZ q1w treatment group (11 weeks of treatment + 12 weeks of follow-up)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Hide Arm/Group Description

ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Placebo

ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.

ALX-0061

Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).

Tocilizumab

All-Cause Mortality
ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/62 (0.00%)      0/62 (0.00%)      0/63 (0.00%)      0/64 (0.00%)    
Hide Serious Adverse Events
ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/62 (1.61%)      0/62 (0.00%)      2/63 (3.17%)      2/64 (3.13%)    
Infections and infestations         
Diverticulitis  1  0/62 (0.00%)  0 0/62 (0.00%)  0 0/63 (0.00%)  0 1/64 (1.56%)  1
Erysipelas  1  0/62 (0.00%)  0 0/62 (0.00%)  0 1/63 (1.59%)  1 0/64 (0.00%)  0
Nail bed infection bacterial  1  0/62 (0.00%)  0 0/62 (0.00%)  0 0/63 (0.00%)  0 1/64 (1.56%)  1
Metabolism and nutrition disorders         
Dehydration  1  0/62 (0.00%)  0 0/62 (0.00%)  0 1/63 (1.59%)  1 0/64 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease  1  1/62 (1.61%)  1 0/62 (0.00%)  0 0/63 (0.00%)  0 0/64 (0.00%)  0
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ALX-0061 150 mg q4w ALX-0061 150 mg q2w ALX-0061 225 mg q2w TCZ 162 mg q1w or q2w
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/62 (24.19%)      20/62 (32.26%)      17/63 (26.98%)      12/64 (18.75%)    
Blood and lymphatic system disorders         
Leukopenia  1  4/62 (6.45%)  5 1/62 (1.61%)  1 0/63 (0.00%)  0 2/64 (3.13%)  2
Neutropenia  1  4/62 (6.45%)  5 3/62 (4.84%)  3 0/63 (0.00%)  0 5/64 (7.81%)  5
Gastrointestinal disorders         
Abdominal pain  1  0/62 (0.00%)  0 4/62 (6.45%)  4 1/63 (1.59%)  1 0/64 (0.00%)  0
General disorders         
Injection site erythema  1  4/62 (6.45%)  7 7/62 (11.29%)  10 5/63 (7.94%)  20 2/64 (3.13%)  2
Infections and infestations         
Alanine aminotransferase increased  1  1/62 (1.61%)  1 0/62 (0.00%)  0 4/63 (6.35%)  5 1/64 (1.56%)  1
Metabolism and nutrition disorders         
Hypercholesterolaemia  1  2/62 (3.23%)  2 5/62 (8.06%)  5 7/63 (11.11%)  7 2/64 (3.13%)  2
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Publication of any results from this study will be according to the principles of the Declaration of Helsinki and will require prior review and written agreement of the Sponsor.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Monitor
Organization: Ablynx NV
Phone: +32 (0)9 262 00 00
EMail: clinicaltrials@ablynx.com
Layout table for additonal information
Responsible Party: Ablynx
ClinicalTrials.gov Identifier: NCT02287922    
Other Study ID Numbers: ALX0061-C202
2014-003012-36 ( EudraCT Number )
First Submitted: November 5, 2014
First Posted: November 11, 2014
Results First Submitted: June 25, 2019
Results First Posted: August 21, 2019
Last Update Posted: August 21, 2019