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

• Sponsor: Ablynx (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02287922
• Collaborator: (none)
• Enrollment: 251
• Locations: 83
• Arms: 4
• Actual Duration (Months): 16
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is:

• To assess the efficacy and safety of dose regimens of ALX-0061 monotherapy administered subcutaneously (s.c.) to subjects with active rheumatoid arthritis (RA).

The secondary objectives of this study are:

• To assess the effects of ALX-0061 on quality of life, the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061 and to explore potential dose regimens for ALX-0061 monotherapy, based on safety and efficacy, for further clinical development.

• To obtain parallel descriptive information concerning the efficacy and safety of tocilizumab (TCZ) s.c. in the same clinical trial RA population.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: ALX-0061; Biological: Placebo; Biological: Tocilizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 251 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase IIb Multicenter, Randomized, Double-blind Study of ALX-0061 Administered Subcutaneously as Monotherapy, in Subjects With Moderate to Severe Rheumatoid Arthritis Who Are Intolerant to Methotrexate or for Whom Continued Methotrexate Treatment is Inappropriate
• Actual Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALX-0061 150 mg q4w 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.	Biological: ALX-0061; Biological: Placebo
Experimental: ALX-0061 150 mg q2w 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.	Biological: ALX-0061; Biological: Placebo
Experimental: ALX-0061 225 mg q2w 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.	Biological: ALX-0061
Active Comparator: TCZ 162 mg q1w or q2w 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).	Biological: Tocilizumab

Outcome Measures

Primary Outcome Measures

1. Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12 [Week 12]

   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.

Secondary Outcome Measures

1. Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 [Week 12]

   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.

2. 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 [Week 12]

   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.

3. Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12 [Week 12]

   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.

4. Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12 [Week 12]

   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.

5. Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12 [Week 12]

   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.

6. Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12 [Week 12]

   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.

7. Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12 [Week 12]

   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.

8. Number and Percentage of Subjects in Remission Using SDAI at Week 12 [Week 12]

   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.

9. Number and Percentage of Subjects in Remission Using CDAI at Week 12 [Week 12]

   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.

10. Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12 [Week 12]

    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.

11. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 [From baseline until Week 12]

    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.

12. Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 [From baseline until week 12]

    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.

13. Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12 [From baseline until Week 12]

    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.

14. Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) [From baseline until Week 12]

    Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).

15. Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12 [From baseline until Week 12]

16. Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response [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)]

17. Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity [From baseline until Week 12]

18. Number of Treatment-emergent Adverse Event by Severity [From baseline until Week 12]

19. Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event [From baseline until Week 12]

    treatment related = considered at least possibly related to study drug by the Investigator

20. Number of Treatment-related Treatment-emergent Adverse Event [From baseline until Week 12]

    treatment related = considered at least possibly related to study drug by the Investigator

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of RA (according to the 2010 EULAR/American College of Rheumatology (ACR) classification criteria) for at least 6 months prior to screening, and ACR functional class I-III.

• Received previous or current treatment with methotrexate (MTX), and is considered intolerant to MTX, or for whom continued treatment with MTX is inappropriate or has contraindications for MTX use.

• Subjects must not have received MTX for at least 4 weeks before first administration of the study drug.

• Have active RA with at least 6 swollen and 6 tender joints(66/68 joint count) at the time of screening and baseline

• Others as defined in the protocol

Exclusion Criteria:

• Have been treated with DMARDs (Disease Modifying Antirheumatic Drugs)/systemic immunosuppressive drugs during the 4 weeks, or 12 weeks for hydroxychloroquine, chloroquine, or leflunomide (except when an adequate wash-out procedure for leflunomide was completed), prior to first administration of study drug.

• Have received approved or investigational biological or targeted synthetic DMARD therapies for RA (including tumor necrosis factor alpha-inhibitors, abatacept, rituximab, or Janus kinase [JAK]-inhibitors) less than 6 months prior to screening.

• Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs (including JAK inhibitors), for RA.

• Have received prior therapy blocking the interleukin-6 (IL-6) pathway, at any time.

• Others as defined in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site	Birmingham	Alabama	United States	35216
2	Investigator Site	Hemet	California	United States	92543
3	Investigator Site	La Palma	California	United States	90712
4	Investigator site	Los Angeles	California	United States	90017
5	Investigator Site	Los Angeles	California	United States	90036
6	Investigator site	Ventura	California	United States	93003
7	Investigator site	Hialeah	Florida	United States	33016
8	Investigator Site	Homestead	Florida	United States	33030
9	Investigator Site	Orlando	Florida	United States	32804
10	Investigator Site	Stockbridge	Georgia	United States	30281
11	Investigator site	Overland Park	Kansas	United States	66209
12	Investigator Site	Worcester	Massachusetts	United States	01605
13	Investigator Site	Albuquerque	New Mexico	United States	87102
14	Investigator Site	New York	New York	United States	10018
15	Investigator Site	Charleston	South Carolina	United States	29406
16	Investigator Site	Memphis	Tennessee	United States	38119
17	Investigator Site	Mesquite	Texas	United States	75150
18	Investigator Site	Brussels		Belgium	1200
19	Investigator Site	Ghent		Belgium	9000
20	Investigator Site	Liège		Belgium	4000
21	Investigator Site	Burgas		Bulgaria
22	Investigator Site	Pleven		Bulgaria
23	Investigator Site 1	Plovdiv		Bulgaria
24	Investigator Site 2	Plovdiv		Bulgaria
25	Investigator Site 1	Ruse		Bulgaria
26	Investigator Site 2	Ruse		Bulgaria
27	Investigator Site	Sofia		Bulgaria
28	Investigator Site	Brno		Czechia	602000
29	Investigator Site	Olomouc		Czechia
30	Investigator Site	Ostrava		Czechia	70300
31	Investigator Site 1	Prague		Czechia
32	Investigator Site 2	Prague		Czechia
33	Investigator Site	Zlin		Czechia
34	Investigator Site	Tbilisi		Georgia	0102
35	Investigator Site 1	Tbilisi		Georgia	0159
36	Investigator Site 2	Tbilisi		Georgia	0159
37	Investigator Site	Tbilisi		Georgia	0160
38	Investigator Site	Tbilisi		Georgia	0179
39	Investigator Site	Berlin		Germany
40	Investigator Site	Frankfurt		Germany
41	Investigator Site	Hamburg		Germany
42	Investigator Site	Baja		Hungary	6500
43	Investigator Site	Budapest		Hungary
44	Investigator Site	Esztergom		Hungary
45	Investigator site	Gyula		Hungary	5700
46	Investigator Site	Szikszo		Hungary	3800
47	Investigator Site	Szombathely		Hungary	9700
48	Investigator Site	Székesfehérvar		Hungary	8000
49	Investigator Site	Veszprém		Hungary	8200
50	Investigator Site	Culiacan		Mexico
51	Investigator Site	Leon		Mexico
52	Investigator Site	Mexico City 1		Mexico
53	Investigator Site 1	Mexico City		Mexico
54	Investigator Site 2	Mexico City		Mexico
55	Investigator Site 1	Monterrey		Mexico
56	Investigator Site 2	Monterrey		Mexico
57	Investigator Site	Chisinau		Moldova, Republic of	2025
58	Investigator Site	Chisinau		Moldova, Republic of
59	Investigator Site 1	Skopje		North Macedonia	1000
60	Investigator Site 2	Skopje		North Macedonia	1000
61	Investigator Site	Bydgoszcz		Poland
62	Investigator Site 2	Elblag		Poland	82300
63	Investigator Site	Elblag		Poland
64	Investigator Site	Gdynia		Poland
65	Investigator Site	Grodzisk Mazowiecki		Poland	05825
66	Investigator Site	Lublin		Poland	20582
67	Investigator SIte	Poznan		Poland	60773
68	Investigator Site	Sochaczew		Poland	96500
69	Investigator Site	Torun		Poland	87100
70	Investigator Site	Warszawa		Poland	02653
71	Investigator Site	Bucharest		Romania
72	Investigator Site	Oradea		Romania
73	Investigator Site	Timisoara		Romania
74	Investigator Site 1	Belgrade		Serbia
75	Investigator Site 2	Belgrade		Serbia
76	Investigator Site 3	Belgrade		Serbia
77	Investigator Site	Niska Banja		Serbia
78	Investigator Site	Cordoba		Spain
79	Investigator Site	Madrid		Spain	28007
80	Investigator Site	Santander		Spain	39300
81	Investigator Site 2	Santander		Spain
82	Investigator Site 1	Santiago de Compostela		Spain
83	Investigator Site 2	Santiago de Compostela		Spain

Sponsors and Collaborators

• Ablynx

Investigators

• Study Director: Medical Monitor, MD, Ablynx

Study Documents (Full-Text)

• Study Protocol - Jul 9, 2015

More Information

Publications

None provided.

• Responsible Party: Ablynx
• ClinicalTrials.gov Identifier: NCT02287922
• Other Study ID Numbers: ALX0061-C202; 2014-003012-36
• First Posted: Nov 11, 2014
• Last Update Posted: Aug 21, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

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
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 Participants	62	62	63	64	251
Age (Count of Participants)
<=18 years	0 0%	1 1.6%	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 (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.0 (12.25)	51.2 (12.05)	51.3 (11.81)	50.0 (12.26)	51.4 (12.07)
Sex: Female, Male (Count of Participants)
Female	49 79%	53 85.5%	54 85.7%	56 87.5%	212 84.5%
Male	13 21%	9 14.5%	9 14.3%	8 12.5%	39 15.5%

Outcome Measures

1. Primary Outcome

Title	Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [Participants]	45 72.6%	48 77.4%	51 81%	50 78.1%

2. Secondary Outcome

Title	Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
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
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [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
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [Participants]	26 41.9%	32 51.6%	34 54%	20 31.3%

5. Secondary Outcome

Title	Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [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
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [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
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [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
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [Participants]	21 33.9%	13 21%	25 39.7%	16 25%

9. Secondary Outcome

Title	Number and Percentage of Subjects in Remission Using SDAI at Week 12
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [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
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [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
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [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
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

Outcome Measure Data

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
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
Measure Participants	61	60	59	64
Mean (Standard Error) [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
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

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
physical component	7.808 (0.8533)	7.979 (1.1895)	8.861 (1.0818)	7.611 (0.9562)
mental component	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
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

Outcome Measure Data

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
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
Measure Participants	58	60	56	57
Mean (Standard Error) [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)
Description	Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).
Time Frame	From baseline until Week 12

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Baseline	33.0 (4.65)	42.3 (8.71)	30.9 (3.72)	31.0 (2.54)
Week 12	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
Time Frame	From baseline until Week 12

Outcome Measure Data

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
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
Measure Participants	54	55	52
Geometric Mean (Standard Deviation) [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
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)

Outcome Measure Data

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
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
Measure Participants	62	62	63	187
Count of Participants [Participants]	7 11.3%	25 40.3%	26 41.3%	58 90.6%

18. Secondary Outcome

Title	Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity
Time Frame	From baseline until Week 12

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Mild	22 35.5%	18 29%	21 33.3%	19 29.7%
Moderate	12 19.4%	13 21%	9 14.3%	10 15.6%
Severe	0 0%	2 3.2%	1 1.6%	2 3.1%

19. Secondary Outcome

Title	Number of Treatment-emergent Adverse Event by Severity
Time Frame	From baseline until Week 12

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
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
Description	treatment related = considered at least possibly related to study drug by the Investigator
Time Frame	From baseline until Week 12

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Count of Participants [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
Description	treatment related = considered at least possibly related to study drug by the Investigator
Time Frame	From baseline until Week 12

Outcome Measure Data

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
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
Measure Participants	62	62	63	64
Number [treatment-emergent adverse events]	46	53	64	32

Adverse Events

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)
Arm/Group Title	ALX-0061 150 mg q4w		ALX-0061 150 mg q2w		ALX-0061 225 mg q2w		TCZ 162 mg q1w or q2w
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/62 (0%)		0/63 (0%)		0/64 (0%)
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 (1.6%)		0/62 (0%)		2/63 (3.2%)		2/64 (3.1%)
Infections and infestations
Diverticulitis	0/62 (0%)	0	0/62 (0%)	0	0/63 (0%)	0	1/64 (1.6%)	1
Erysipelas	0/62 (0%)	0	0/62 (0%)	0	1/63 (1.6%)	1	0/64 (0%)	0
Nail bed infection bacterial	0/62 (0%)	0	0/62 (0%)	0	0/63 (0%)	0	1/64 (1.6%)	1
Metabolism and nutrition disorders
Dehydration	0/62 (0%)	0	0/62 (0%)	0	1/63 (1.6%)	1	0/64 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/62 (1.6%)	1	0/62 (0%)	0	0/63 (0%)	0	0/64 (0%)	0
Other (Not Including 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	15/62 (24.2%)		20/62 (32.3%)		17/63 (27%)		12/64 (18.8%)
Blood and lymphatic system disorders
Leukopenia	4/62 (6.5%)	5	1/62 (1.6%)	1	0/63 (0%)	0	2/64 (3.1%)	2
Neutropenia	4/62 (6.5%)	5	3/62 (4.8%)	3	0/63 (0%)	0	5/64 (7.8%)	5
Gastrointestinal disorders
Abdominal pain	0/62 (0%)	0	4/62 (6.5%)	4	1/63 (1.6%)	1	0/64 (0%)	0
General disorders
Injection site erythema	4/62 (6.5%)	7	7/62 (11.3%)	10	5/63 (7.9%)	20	2/64 (3.1%)	2
Infections and infestations
Alanine aminotransferase increased	1/62 (1.6%)	1	0/62 (0%)	0	4/63 (6.3%)	5	1/64 (1.6%)	1
Metabolism and nutrition disorders
Hypercholesterolaemia	2/62 (3.2%)	2	5/62 (8.1%)	5	7/63 (11.1%)	7	2/64 (3.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.