Trial Outcomes & Findings for A Dose-Range Finding Study for ALX-0061 Combination Therapy in Subjects With Rheumatoid Arthritis (NCT NCT02309359)

NCT ID: NCT02309359

Last Updated: 2019-08-21

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 345 participants
• Primary outcome timeframe: Week 12
• Results posted on: 2019-08-21

Participant Flow

A total of 345 subjects were recruited at 63 sites located in Europe (46 sites; 259 subjects), Latin America (7 sites; 59 subjects) and North America (10 sites; 27 subjects). Consent was obtained from the first subject on 30 Jan 2015; the last subject completed the final visit on 8 Aug 2016.

Of the 712 subjects screened, 367 were screen failures and 345 were randomly assigned to treatment (Intent-to-treat population). All subjects enrolled received study drug and were included in the safety population. All subjects who received at least one dose of ALX-0061 (i.e., 276 subjects) were included in the pharmacokinetic (PK) population.

Participant milestones

Measure	ALX-0061 75 mg q4w + MTX ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + Methotrexate (MTX; at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).
Overall Study STARTED	69	70	68	69	69
Overall Study COMPLETED	57	62	57	57	60
Overall Study NOT COMPLETED	12	8	11	12	9

Reasons for withdrawal

Measure	ALX-0061 75 mg q4w + MTX ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + Methotrexate (MTX; at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).
Overall Study Adverse Event	4	5	5	4	4
Overall Study Death	1	0	0	0	0
Overall Study Withdrawal by Subject	2	2	4	4	0
Overall Study Lack of Efficacy	3	1	0	0	3
Overall Study Lost to Follow-up	0	0	0	1	0
Overall Study Other	2	0	2	3	2

Baseline Characteristics

A Dose-Range Finding Study for ALX-0061 Combination Therapy in Subjects With Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Total n=345 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	59 Participants n=5 Participants	58 Participants n=7 Participants	56 Participants n=5 Participants	55 Participants n=4 Participants	56 Participants n=21 Participants	284 Participants n=10 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	14 Participants n=4 Participants	13 Participants n=21 Participants	60 Participants n=10 Participants
Age, Continuous	53.3 years STANDARD_DEVIATION 10.35 • n=5 Participants	52 years STANDARD_DEVIATION 13.16 • n=7 Participants	51.9 years STANDARD_DEVIATION 11.93 • n=5 Participants	52.3 years STANDARD_DEVIATION 13.36 • n=4 Participants	52.8 years STANDARD_DEVIATION 11.92 • n=21 Participants	52.4 years STANDARD_DEVIATION 12.14 • n=10 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	62 Participants n=7 Participants	59 Participants n=5 Participants	55 Participants n=4 Participants	55 Participants n=21 Participants	289 Participants n=10 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	14 Participants n=4 Participants	14 Participants n=21 Participants	56 Participants n=10 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Intent-to-treat population

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12	52 Participants	57 Participants	53 Participants	50 Participants	43 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

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

This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 24 were treated as non responders.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With ACR20 Response at Week 24	51 Participants	55 Participants	49 Participants	52 Participants	51 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

ACR50 response is defined as:

• 50% improvement in TJC (68 joints) relative to Week 0 AND
• 50% improvement in SJC (66 joints) relative to Week 0 AND
• 50% 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 the concerned visit were treated as non responders.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 Week 12	20 Participants	31 Participants	28 Participants	31 Participants	19 Participants	—
Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 Week 24	33 Participants	39 Participants	37 Participants	42 Participants	27 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

ACR70 response is defined as:

• 70% improvement in TJC (68 joints) relative to Week 0 AND
• 70% improvement in SJC (66 joints) relative to Week 0 AND
• 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 the concerned visit were treated as non responders.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 Week 12	10 Participants	15 Participants	13 Participants	12 Participants	6 Participants	—
Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 Week 24	16 Participants	23 Participants	15 Participants	31 Participants	12 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

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

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

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 Week 12	16 Participants	37 Participants	32 Participants	40 Participants	16 Participants	—
Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 Week 24	26 Participants	40 Participants	41 Participants	48 Participants	20 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 Week 12	13 Participants	36 Participants	29 Participants	33 Participants	11 Participants	—
Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 Week 24	24 Participants	38 Participants	33 Participants	46 Participants	13 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

SDAI = TJC28 + SJC28 + Patient's Global Assessment of Disease Activity (VASPA) + Physician's Global Assessment of Disease Activity (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 NRI, i.e., subjects with missing response at the concerned visit were treated as non responders.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 Week 12	49 Participants	34 Participants	29 Participants	25 Participants	17 Participants	—
Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 Week 24	29 Participants	34 Participants	35 Participants	46 Participants	22 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 Week 12	22 Participants	31 Participants	26 Participants	23 Participants	17 Participants	—
Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 Week 24	29 Participants	33 Participants	29 Participants	43 Participants	23 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 Week 12	15 Participants	36 Participants	30 Participants	39 Participants	15 Participants	—
Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 Week 24	26 Participants	39 Participants	39 Participants	47 Participants	19 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 Week 12	3 Participants	26 Participants	15 Participants	21 Participants	6 Participants	—
Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 Week 24	17 Participants	26 Participants	23 Participants	37 Participants	8 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 Week 12	2 Participants	8 Participants	6 Participants	5 Participants	3 Participants	—
Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 Week 24	7 Participants	13 Participants	10 Participants	14 Participants	6 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat Population

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 Week 12	3 Participants	7 Participants	4 Participants	5 Participants	3 Participants	—
Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 Week 24	10 Participants	13 Participants	8 Participants	13 Participants	7 Participants	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent-to-treat population

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 non-responder imputation (NRI), i.e., subjects with missing response at the concerned visit were treated as non responders.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 Week 12	0 Participants	5 Participants	2 Participants	4 Participants	3 Participants	—
Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 Week 24	6 Participants	9 Participants	6 Participants	13 Participants	6 Participants	—

SECONDARY outcome

Timeframe: from baseline till Week 24

Population: Intent-to-treat population

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 Week 12	-0.696 score on a scale Standard Error 0.0857	-0.619 score on a scale Standard Error 0.0657	-0.771 score on a scale Standard Error 0.0763	-0.615 score on a scale Standard Error 0.0858	-0.613 score on a scale Standard Error 0.0718	—
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 Week 24	-0.82 score on a scale Standard Error 0.0913	-0.665 score on a scale Standard Error 0.0682	-0.876 score on a scale Standard Error 0.0802	-0.772 score on a scale Standard Error 0.0926	-0.662 score on a scale Standard Error 0.0798	—

SECONDARY outcome

Timeframe: from baseline till Week 24

Population: Intent-to-treat population; "Number Analyzed" reflect the number of non-missing, non-imputed observations at that specific timepoint.

The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 Week 12	7.372 score on a scale Standard Error 0.9136	7.100 score on a scale Standard Error 0.7477	6.534 score on a scale Standard Error 0.8878	7.778 score on a scale Standard Error 0.994	5.413 score on a scale Standard Error 0.7813	—
Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 Week 24	10.412 score on a scale Standard Error 1.0642	8.725 score on a scale Standard Error 0.9194	8.835 score on a scale Standard Error 1.009	10.762 score on a scale Standard Error 1.1497	7.255 score on a scale Standard Error 0.9483	—

SECONDARY outcome

Timeframe: from baseline till Week 24

Population: Intent-to-treat population; "Number Analyzed" reflect the number of non-missing, non-imputed observations at that specific timepoint.

The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 Week 12	9.096 score on a scale Standard Error 1.4966	7.249 score on a scale Standard Error 1.1237	9.749 score on a scale Standard Error 1.4177	5.686 score on a scale Standard Error 1.6485	5.569 score on a scale Standard Error 1.6467	—
Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 Week 24	9.857 score on a scale Standard Error 1.5326	7.962 score on a scale Standard Error 1.3932	11.739 score on a scale Standard Error 1.4159	8.981 score on a scale Standard Error 1.6876	6.198 score on a scale Standard Error 1.696	—

SECONDARY outcome

Timeframe: from baseline till Week 24

Population: Intent-to-treat population; "Number Analyzed" reflect the number of non-missing, non-imputed observations at that specific timepoint.

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.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 Week 12	11.014 score on a scale Standard Error 1.3593	8.63 score on a scale Standard Error 1.0465	10.884 score on a scale Standard Error 1.5424	9.389 score on a scale Standard Error 1.3706	6.381 score on a scale Standard Error 1.2026	—
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 Week 24	12.446 score on a scale Standard Error 1.5687	10.439 score on a scale Standard Error 1.2157	13.374 score on a scale Standard Error 1.5621	12.381 score on a scale Standard Error 1.5193	6.712 score on a scale Standard Error 1.4651	—

SECONDARY outcome

Timeframe: at Week 12 and Week 24 visits

Population: PK population

ALX-0061 concentrations were only measured in samples of subjects randomized to any of the ALX-0061 treatment arms. Samples were taken predose at the concerned visits.

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 Week 12	0.163 micrograms/milliliter Standard Deviation 3.7	1.79 micrograms/milliliter Standard Deviation 3.08	19.9 micrograms/milliliter Standard Deviation 1.56	32.1 micrograms/milliliter Standard Deviation 1.43	—	—
Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 Week 24	0.122 micrograms/milliliter Standard Deviation 2.56	1.64 micrograms/milliliter Standard Deviation 3.11	20.9 micrograms/milliliter Standard Deviation 1.5	35.2 micrograms/milliliter Standard Deviation 1.37	—	—

SECONDARY outcome

Timeframe: from baseline till Week 24

Population: Safety Population; "Number Analyzed" reflect the number of subjects with data available at that specific timepoint.

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

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 Baseline	26.9 ng/mL Standard Error 0.995	29.2 ng/mL Standard Error 1.04	27.7 ng/mL Standard Error 0.78	28.9 ng/mL Standard Error 1.05	28.9 ng/mL Standard Error 1.1	—
Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 Week 12	166 ng/mL Standard Error 16.7	420 ng/mL Standard Error 21	519 ng/mL Standard Error 16.8	488 ng/mL Standard Error 16.8	52.9 ng/mL Standard Error 14.1	—
Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 Week 24	150 ng/mL Standard Error 12.9	422 ng/mL Standard Error 17.8	484 ng/mL Standard Error 16.3	487 ng/mL Standard Error 14.3	35.4 ng/mL Standard Error 6.6	—

SECONDARY outcome

Timeframe: from baseline till follow-up (FU) (i.e., 12 weeks after last study drug dosing at Week 22 or after early treatment discontinuation)

Population: Safety population

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total n=276 Participants All participants who received ALX-0061
Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response	9 Participants	16 Participants	31 Participants	33 Participants	13 Participants	89 Participants

SECONDARY outcome

Timeframe: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit

Population: Safety population

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity Mild	21 Participants	28 Participants	23 Participants	20 Participants	20 Participants	—
Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity Moderate	15 Participants	12 Participants	19 Participants	20 Participants	14 Participants	—
Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity Severe	6 Participants	4 Participants	2 Participants	4 Participants	2 Participants	—

SECONDARY outcome

Timeframe: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit

Population: Safety population

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number of Treatment-emergent Adverse Events by Severity Moderate	34 Adverse events	24 Adverse events	26 Adverse events	40 Adverse events	22 Adverse events	—
Number of Treatment-emergent Adverse Events by Severity Mild	66 Adverse events	78 Adverse events	66 Adverse events	56 Adverse events	49 Adverse events	—
Number of Treatment-emergent Adverse Events by Severity Severe	6 Adverse events	5 Adverse events	4 Adverse events	5 Adverse events	2 Adverse events	—

SECONDARY outcome

Timeframe: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit

Population: Safety population

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events	26 Participants	25 Participants	26 Participants	25 Participants	18 Participants	—

SECONDARY outcome

Timeframe: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit

Population: Safety population

Outcome measures

Measure	ALX-0061 75 mg q4w + MTX n=69 Participants ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 Participants ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 Participants ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 Participants ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 Participants Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 Total All participants who received ALX-0061
Number of Treatment-related Treatment-emergent Adverse Events	55 Adverse events	52 Adverse events	46 Adverse events	47 Adverse events	21 Adverse events	—

Adverse Events

ALX-0061 75 mg q4w + MTX

Serious events: 5 serious events

Other events: 29 other events

Deaths: 1 deaths

ALX-0061 150 mg q4w + MTX

Serious events: 5 serious events

Other events: 34 other events

Deaths: 0 deaths

ALX-0061 150 mg q2w + MTX

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

ALX-0061 225 mg q2w + MTX

Serious events: 2 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo q2w + MTX

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	ALX-0061 75 mg q4w + MTX n=69 participants at risk ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 participants at risk ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 participants at risk ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 participants at risk ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 participants at risk Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/69 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Cardiac disorders Cardiac arrest	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Blood and lymphatic system disorders Cytopenia	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/70 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Gastrointestinal disorders Gastritis	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Skin and subcutaneous tissue disorders Angioedema	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/70 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Arthritis bacterial	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Cellulitis	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/70 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Ear infection	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Herpes Zoster	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Pneumonia	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/70 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Sepsis	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/70 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Gastrointestinal disorders Large intestine perforation	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Pharyngitis	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/70 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Staphylococcal sepsis	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Intervertebral discitis	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/70 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).

Other adverse events

Measure	ALX-0061 75 mg q4w + MTX n=69 participants at risk ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q4w + MTX n=70 participants at risk ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 150 mg q2w + MTX n=68 participants at risk ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	ALX-0061 225 mg q2w + MTX n=69 participants at risk ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. ALX-0061 Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).	Placebo q2w + MTX n=69 participants at risk Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. Placebo Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor).
Vascular disorders Hypertension	4.3% 3/69 • Number of events 3 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/70 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	4.4% 3/68 • Number of events 3 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	5.8% 4/69 • Number of events 5 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Investigations Alanine aminotransferase increased	2.9% 2/69 • Number of events 3 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/70 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/68 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	8.7% 6/69 • Number of events 7 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Investigations Aspartate aminotransferase increased	2.9% 2/69 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/70 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.5% 1/68 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	7.2% 5/69 • Number of events 6 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Blood and lymphatic system disorders Neutropenia	5.8% 4/69 • Number of events 7 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/70 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/68 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
General disorders Injection site erythema	5.8% 4/69 • Number of events 5 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	7.1% 5/70 • Number of events 7 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	10.3% 7/68 • Number of events 8 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	4.3% 3/69 • Number of events 3 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Metabolism and nutrition disorders Hypercholesterolaemia	2.9% 2/69 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	10.0% 7/70 • Number of events 7 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	5.9% 4/68 • Number of events 6 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	7.2% 5/69 • Number of events 6 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	5.8% 4/69 • Number of events 4 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Bronchitis	8.7% 6/69 • Number of events 7 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/70 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	4.4% 3/68 • Number of events 3 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	4.3% 3/69 • Number of events 3 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	4.3% 3/69 • Number of events 3 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Nasopharyngitis	5.8% 4/69 • Number of events 4 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	7.1% 5/70 • Number of events 5 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/68 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	5.8% 4/69 • Number of events 4 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	8.7% 6/69 • Number of events 6 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Pharyngitis	2.9% 2/69 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	8.6% 6/70 • Number of events 6 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	4.4% 3/68 • Number of events 4 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/69 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).
Infections and infestations Upper respiratory tract infection	0.00% 0/69 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	1.4% 1/70 • Number of events 1 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	2.9% 2/68 • Number of events 2 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	10.1% 7/69 • Number of events 7 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).	4.3% 3/69 • Number of events 3 • From first study drug intake up to and including follow-up, i.e., maximum of 34 weeks (22 weeks of treatment + 12 weeks of follow-up).

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Publication of any results from this study will be according to the principles of the Declaration of Helsinki, and will require prior review and written agreement of the Sponsor.
• Publication restrictions are in place

Restriction type: OTHER