A Dose-Range Finding Study for ALX-0061 Combination Therapy in Subjects With Rheumatoid Arthritis
Sponsor
Ablynx (Industry)
Overall Status
Completed
CT.gov ID
NCT02309359
Collaborator
(none)
345
94
5
19
3.7
0.2
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy and safety of dose regimens of ALX-0061 administered subcutaneously (s.c.) in combination with methotrexate (MTX) to subjects with active rheumatoid arthritis (RA) despite MTX therapy, compared with placebo.
To assess the effects of ALX-0061 on quality of life, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061, and to define the optimal dose regimen for ALX-0061, based on safety and efficacy, for further clinical development.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Subjects who completed the 24-week assessment period and achieved at least 20% improvement in swollen joint count (SJC) and/or tender joint count (TJC) at Week 24 of study ALX0061-C201 were invited to participate in an open-label extension (OLE) study ALX0061-C203 (NCT02518620), if the study was approved in their country and selection criteria were met.
Study Design
Study Type:
Interventional
Actual Enrollment
:
345 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase IIb Multicenter, Randomized, Double-blind, Placebo-Controlled Dose-Range Finding Study of ALX-0061 Administered Subcutaneously in Combination With Methotrexate, in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
Study Start Date
:
Jan 1, 2015
Actual Primary Completion Date
:
Aug 1, 2016
Actual Study Completion Date
:
Aug 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: 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. |
Other: Placebo
Drug: Methotrexate
Stable background dose of commercially available methotrexate (not provided by the Sponsor).
|
| Experimental: ALX-0061 75 mg q4w + MTX 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. |
Biological: ALX-0061
Other: Placebo
Drug: Methotrexate
Stable background dose of commercially available methotrexate (not provided by the Sponsor).
|
| Experimental: 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. |
Biological: ALX-0061
Other: Placebo
Drug: Methotrexate
Stable background dose of commercially available methotrexate (not provided by the Sponsor).
|
| Experimental: 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. |
Biological: ALX-0061
Other: Placebo
Drug: Methotrexate
Stable background dose of commercially available methotrexate (not provided by the Sponsor).
|
| Experimental: 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. |
Biological: ALX-0061
Drug: Methotrexate
Stable background dose of commercially available methotrexate (not provided by the Sponsor).
|
Outcome Measures
Primary Outcome Measures
- Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12 [Week 12]
ACR 20 response is defined as: 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND 20% improvement in 3 of the following 5 areas relative to Week 0: Subject's Assessment of Pain (100 mm - visual analogue scale [VAS]) Subject's Global Assessment of Disease Activity (VASPA) Physician's Global Assessment of Disease Activity (VASPHA) Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non responders.
Secondary Outcome Measures
- Number and Percentage of Subjects With ACR20 Response at Week 24 [24 weeks]
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.
- Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 [24 weeks]
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.
- Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 [24 weeks]
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.
- 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 [24 weeks]
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.
- Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 [24 weeks]
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.
- Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 [24 weeks]
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.
- Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 [24 weeks]
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.
- Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 [24 weeks]
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.
- Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 [24 weeks]
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.
- Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 [24 weeks]
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.
- Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 [24 weeks]
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.
- Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 [24 weeks]
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.
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 [from baseline till Week 24]
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.
- Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 [from baseline till Week 24]
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.
- Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 [from baseline till Week 24]
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.
- Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 [from baseline till Week 24]
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.
- Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 [at Week 12 and Week 24 visits]
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.
- Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 [from baseline till Week 24]
Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).
- Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response [from baseline till follow-up (FU) (i.e., 12 weeks after last study drug dosing at Week 22 or after early treatment discontinuation)]
- Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity [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]
- Number of Treatment-emergent Adverse Events by Severity [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]
- Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events [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]
- Number of Treatment-related Treatment-emergent Adverse Events [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]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 74 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of RA for at least 6 months prior to screening, and American College of Rheumatology (ACR) functional class I-III
-
Subjects treated with and tolerating MTX
-
Active RA
-
Others as defined in the protocol
Exclusion Criteria:
-
Have been treated with disease-modifying antirheumatic drugs (DMARDs)/systemic immunosuppressives other than MTX.
-
Have received approved or investigational biological or targeted synthetic DMARD therapies for RA less than 6 months prior to screening.
-
Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs, for RA.
-
Have received prior therapy blocking the interleukin-6 (IL-6) pathway, at any time.
-
Others as defined in the protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigator Site | Birmingham | Alabama | United States | 35216 |
| 2 | Investigator Site | Hemet | California | United States | 92543 |
| 3 | Investigator Site | La Palma | California | United States | 90712 |
| 4 | Investigator Site | Los Angeles | California | United States | 90017 |
| 5 | Investigator site | Los Angeles | California | United States | 90036 |
| 6 | Investigator Site | Ventura | California | United States | 93003 |
| 7 | Investigator Sites | Hialeah | Florida | United States | 33016 |
| 8 | Investigator Site | Homestead | Florida | United States | 33030 |
| 9 | Investigator Site | Miami Lakes | Florida | United States | 33016 |
| 10 | Investigator Site | Miami | Florida | United States | 33135 |
| 11 | Investigator Site | Orlando | Florida | United States | 32804 |
| 12 | Investigator Site | Stockbridge | Georgia | United States | 30281 |
| 13 | Investigator Site | Overland Park | Kansas | United States | 66209 |
| 14 | Investigator Site | Monroe | Louisiana | United States | 71203 |
| 15 | Investigator Site | Worcester | Massachusetts | United States | 01605 |
| 16 | Investigator Site | Albuquerque | New Mexico | United States | 87102 |
| 17 | Investigator Site | Brooklyn | New York | United States | 11201 |
| 18 | Investigator Site | New York | New York | United States | 10018 |
| 19 | Investigator Sie | Charleston | South Carolina | United States | 29406 |
| 20 | Investigator Site | Myrtle Beach | South Carolina | United States | 29572 |
| 21 | Investigator Site | Memphis | Tennessee | United States | 38119 |
| 22 | Investigator Site | Mesquite | Texas | United States | 75150 |
| 23 | Investigator Site | Brussels | Belgium | 1070 | |
| 24 | Investigator Site | Brussels | Belgium | 1200 | |
| 25 | Investigator Site | Ghent | Belgium | 9000 | |
| 26 | Investigator Site | Liège | Belgium | 4000 | |
| 27 | Investigator Site | Pleven | Bulgaria | 5800 | |
| 28 | Investigator Site | Plovdiv | Bulgaria | 4001 | |
| 29 | Investigator Site 1 | Ruse | Bulgaria | 7000 | |
| 30 | Investigator Site 2 | Ruse | Bulgaria | 7000 | |
| 31 | Investigator Site | Sofia | Bulgaria | 1233 | |
| 32 | Investigator Site | Sofia | Bulgaria | 1612 | |
| 33 | Investigator Site | Varna | Bulgaria | 9000 | |
| 34 | Investigator Site | Brno | Czechia | 60200 | |
| 35 | Investigator Site | Olomouc | Czechia | 77900 | |
| 36 | Investigator Site | Prague | Czechia | 12850 | |
| 37 | Investigator Site | Prague | Czechia | ||
| 38 | Investigator Site | Zlin | Czechia | 76001 | |
| 39 | Investigator Site | Tbilisi | Georgia | 0102 | |
| 40 | Investigator Site 1 | Tbilisi | Georgia | 0159 | |
| 41 | Investigator Site 2 | Tbilisi | Georgia | 0159 | |
| 42 | Investigator Site | Tbilisi | Georgia | 0160 | |
| 43 | Investigator Site | Tbilisi | Georgia | 0179 | |
| 44 | Investigator Site | Bad Nauheim | Germany | 61231 | |
| 45 | Investigator Site | Berlin | Germany | 10117 | |
| 46 | Investigator Site | Berlin | Germany | ||
| 47 | Investigator Site | Cologne | Germany | 50973 | |
| 48 | Investigator Site | Frankfurt | Germany | ||
| 49 | Investigator Site | Hamburg | Germany | 22081 | |
| 50 | Investigator Site | Baja | Hungary | 6500 | |
| 51 | Investigator Site | Balatonfüred | Hungary | 8230 | |
| 52 | Investigator Site | Budapest | Hungary | 1038 | |
| 53 | Investigator Site | Békéscsaba | Hungary | 5600 | |
| 54 | Investigator Site | Gyula | Hungary | 5700 | |
| 55 | Investigator Site | Szikszó | Hungary | 3800 | |
| 56 | Investigator Site | Székesfehérvar | Hungary | 8000 | |
| 57 | Investigator Site | Veszprém | Hungary | 8200 | |
| 58 | Investigator Site | Culiacan | Mexico | 80000 | |
| 59 | Investigator Site | Leon | Mexico | 37000 | |
| 60 | Investigator Site | Merida | Mexico | 97070 | |
| 61 | Investigator Site 1 | Mexico City | Mexico | 03100 | |
| 62 | Investigator Site 2 | Mexico City | Mexico | 06700 | |
| 63 | Investigator Site | Monclova | Mexico | 25714 | |
| 64 | Investigator Site | Monterey | Mexico | 64000 | |
| 65 | Investigator Site | Monterey | Mexico | 64460 | |
| 66 | Investigator Site | Chisinau | Moldova, Republic of | 2025 | |
| 67 | Investigator Site 1 | Skopje | North Macedonia | 1000 | |
| 68 | Investigator Site 2 | Skopje | North Macedonia | 1000 | |
| 69 | Investigator Site | Bydgoszcz | Poland | 85168 | |
| 70 | Investigator Site | Elblag | Poland | 82300 | |
| 71 | Investigator Site | Elblag | Poland | ||
| 72 | Investigator Site | Gdynia | Poland | 81338 | |
| 73 | Investigator Site | Grodzisk Mazowiecki | Poland | 05825 | |
| 74 | Investigator Site | Katowice | Poland | 40954 | |
| 75 | Investigator Site | Lublin | Poland | 20582 | |
| 76 | Investigator Site | Poznan | Poland | 60773 | |
| 77 | Investigator Site | Sochaczew | Poland | 96500 | |
| 78 | Investigator Site | Torun | Poland | 87100 | |
| 79 | Investigator Site | Warszawa | Poland | 02653 | |
| 80 | Investigator Site | Braila | Romania | 800578 | |
| 81 | Investigator Site | Bucharest | Romania | 010976 | |
| 82 | Investigator Site | Bucharest | Romania | 020475 | |
| 83 | Investigator Site | Oradea | Romania | 410028 | |
| 84 | Investigator Site | Targu Mures | Romania | 540142 | |
| 85 | Investigator Site | Timisoara | Romania | 300057 | |
| 86 | Investigator Site 1 | Belgrade | Serbia | 11000 | |
| 87 | Investigator Site 2 | Belgrade | Serbia | 11000 | |
| 88 | Investigator Site 3 | Belgrade | Serbia | 11000 | |
| 89 | Investigator Site | Niska Banja | Serbia | 18205 | |
| 90 | Investigator Site | Novi Sad | Serbia | 21112 | |
| 91 | Investigator Site | Madrid | Spain | 28007 | |
| 92 | Investigator Site | Madrid | Spain | 28041 | |
| 93 | Investigator Site | Salamanca | Spain | 37007 | |
| 94 | Investigator Site | Santiago de Compostela | Spain | 15702 |
Sponsors and Collaborators
- Ablynx
Investigators
- Study Director: Ablynx Clinical Department, Ablynx
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Ablynx
ClinicalTrials.gov Identifier:
NCT02309359
Other Study ID Numbers:
- ALX0061-C201
- 2014-003033-26
First Posted:
Dec 5, 2014
Last Update Posted:
Aug 21, 2019
Last Verified:
Aug 1, 2019
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Period Title: Overall Study | |||||
| STARTED | 69 | 70 | 68 | 69 | 69 |
| COMPLETED | 57 | 62 | 57 | 57 | 60 |
| NOT COMPLETED | 12 | 8 | 11 | 12 | 9 |
Baseline Characteristics
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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 of all reporting groups |
| Overall Participants | 69 | 70 | 68 | 69 | 69 | 345 |
| Age (Count of Participants) | ||||||
| <=18 years |
0
0%
|
1
1.4%
|
0
0%
|
0
0%
|
0
0%
|
1
0.3%
|
| Between 18 and 65 years |
59
85.5%
|
58
82.9%
|
56
82.4%
|
55
79.7%
|
56
81.2%
|
284
82.3%
|
| >=65 years |
10
14.5%
|
11
15.7%
|
12
17.6%
|
14
20.3%
|
13
18.8%
|
60
17.4%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
53.3
(10.35)
|
52
(13.16)
|
51.9
(11.93)
|
52.3
(13.36)
|
52.8
(11.92)
|
52.4
(12.14)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
58
84.1%
|
62
88.6%
|
59
86.8%
|
55
79.7%
|
55
79.7%
|
289
83.8%
|
| Male |
11
15.9%
|
8
11.4%
|
9
13.2%
|
14
20.3%
|
14
20.3%
|
56
16.2%
|
Outcome Measures
| Title | Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12 |
|---|---|
| Description | ACR 20 response is defined as: 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND 20% improvement in 3 of the following 5 areas relative to Week 0: Subject's Assessment of Pain (100 mm - visual analogue scale [VAS]) Subject's Global Assessment of Disease Activity (VASPA) Physician's Global Assessment of Disease Activity (VASPHA) Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non responders. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Count of Participants [Participants] |
52
75.4%
|
57
81.4%
|
53
77.9%
|
50
72.5%
|
43
62.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ALX-0061 75 mg q4w + MTX, ALX-0061 150 mg q4w + MTX, ALX-0061 150 mg q2w + MTX, ALX-0061 225 mg q2w + MTX, Placebo q2w + MTX |
|---|---|---|
| Comments | The null hypothesis of this test was that there is no difference in the percentage of subjects achieving ACR20 response between the treatment groups and the alternative hypothesis was that the percentage of subjects achieving ACR20 response increases with increasing dose level. | |
| Type of Statistical Test | Other | |
| Comments | Under the assumption of monotonicity, a Cochran-Armitage trend test was performed as the primary efficacy analysis. Data were analyzed according to the intent-to-treat (ITT) principle; thus, subjects were analyzed according to the treatment to which they were assigned. Subjects with missing ACR20 response at Week 12 were treated as non responders (non responder imputation approach). | |
| Statistical Test of Hypothesis | p-Value | 0.172 |
| Comments | ||
| Method | Cochran-Armitage trend test | |
| Comments | ||
| Title | Number and Percentage of Subjects With ACR20 Response at Week 24 |
|---|---|
| Description | ACR 20 response is defined as: 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND 20% improvement in 3 of the following 5 areas relative to Week 0: Subject's Assessment of Pain (100 mm - visual analogue scale [VAS]) Subject's Global Assessment of Disease Activity (VASPA) Physician's Global Assessment of Disease Activity (VASPHA) Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) C-reactive protein (CRP) level This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 24 were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Count of Participants [Participants] |
51
73.9%
|
55
78.6%
|
49
72.1%
|
52
75.4%
|
51
73.9%
|
| Title | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 |
|---|---|
| Description | 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. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
20
29%
|
31
44.3%
|
28
41.2%
|
31
44.9%
|
19
27.5%
|
| Week 24 |
33
47.8%
|
39
55.7%
|
37
54.4%
|
42
60.9%
|
27
39.1%
|
| Title | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 |
|---|---|
| Description | 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. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
10
14.5%
|
15
21.4%
|
13
19.1%
|
12
17.4%
|
6
8.7%
|
| Week 24 |
16
23.2%
|
23
32.9%
|
15
22.1%
|
31
44.9%
|
12
17.4%
|
| Title | 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 |
|---|---|
| Description | DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln[CRP+1]) + (0.014 × VASPA) + 0.96 Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
16
23.2%
|
37
52.9%
|
32
47.1%
|
40
58%
|
16
23.2%
|
| Week 24 |
26
37.7%
|
40
57.1%
|
41
60.3%
|
48
69.6%
|
20
29%
|
| Title | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 |
|---|---|
| Description | DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln[ESR]) +(0.014 × VASPA) Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
13
18.8%
|
36
51.4%
|
29
42.6%
|
33
47.8%
|
11
15.9%
|
| Week 24 |
24
34.8%
|
38
54.3%
|
33
48.5%
|
46
66.7%
|
13
18.8%
|
| Title | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 |
|---|---|
| Description | 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. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
49
71%
|
34
48.6%
|
29
42.6%
|
25
36.2%
|
17
24.6%
|
| Week 24 |
29
42%
|
34
48.6%
|
35
51.5%
|
46
66.7%
|
22
31.9%
|
| Title | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 |
|---|---|
| Description | CDAI = TJC28 + SJC28 + VASPA + VASPHA Low disease activity: 2.8 < CDAI ≤ 10 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
22
31.9%
|
31
44.3%
|
26
38.2%
|
23
33.3%
|
17
24.6%
|
| Week 24 |
29
42%
|
33
47.1%
|
29
42.6%
|
43
62.3%
|
23
33.3%
|
| Title | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 |
|---|---|
| Description | EULAR good response is defined as an improvement of >1.2 in DAS28 (CRP) relative to baseline. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
15
21.7%
|
36
51.4%
|
30
44.1%
|
39
56.5%
|
15
21.7%
|
| Week 24 |
26
37.7%
|
39
55.7%
|
39
57.4%
|
47
68.1%
|
19
27.5%
|
| Title | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 |
|---|---|
| Description | DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln[ESR]) +(0.014 × VASPA) Remission = DAS28(ESR) < 2.6 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
3
4.3%
|
26
37.1%
|
15
22.1%
|
21
30.4%
|
6
8.7%
|
| Week 24 |
17
24.6%
|
26
37.1%
|
23
33.8%
|
37
53.6%
|
8
11.6%
|
| Title | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 |
|---|---|
| Description | SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL) Remission: SDAI ≤ 3.3 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
2
2.9%
|
8
11.4%
|
6
8.8%
|
5
7.2%
|
3
4.3%
|
| Week 24 |
7
10.1%
|
13
18.6%
|
10
14.7%
|
14
20.3%
|
6
8.7%
|
| Title | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 |
|---|---|
| Description | CDAI = TJC28 + SJC28 + VASPA + VASPHA Remission: CDAI ≤ 2.8 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat Population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
3
4.3%
|
7
10%
|
4
5.9%
|
5
7.2%
|
3
4.3%
|
| Week 24 |
10
14.5%
|
13
18.6%
|
8
11.8%
|
13
18.8%
|
7
10.1%
|
| Title | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 |
|---|---|
| Description | Boolean remission: tender joint count (TJC)28 ≤ 1 and swollen joint count (SJC)28 ≤ 1 and VASPA (cm) ≤ 1 and CRP (mg/dL) ≤ 1 This endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing response at the concerned visit were treated as non responders. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
0
0%
|
5
7.1%
|
2
2.9%
|
4
5.8%
|
3
4.3%
|
| Week 24 |
6
8.7%
|
9
12.9%
|
6
8.8%
|
13
18.8%
|
6
8.7%
|
| Title | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 |
|---|---|
| Description | The HAQ-DI is a 20-question instrument which assesses the degree of difficulty the subject had in accomplishing tasks in 8 functional areas over the previous week. The 8 areas are: dressing and grooming, hygiene, arising, reach, eating, grip, walking, common daily activities. Within each area, subjects report the amount of difficulty they have in performing the specific items. There are 4 response options ranging from: 0 = No Difficulty, 1 = With Some Difficulty, 2 = With Much Difficulty, 3 = Unable to Do. The 8 areas are each given a single score equal to the maximum value of their component activities (0, 1, 2, or 3). The sum of the area scores is then divided by the number of areas answered to obtain the final HAQ score (rounded to the nearest value evenly divisible by 0.125). The final HAQ-DI score ranges from 0 to 3. A high score means a high degree of disability (=worse outcome). Missing values were imputed with the last non-missing observation. |
| Time Frame | from baseline till Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
-0.696
(0.0857)
|
-0.619
(0.0657)
|
-0.771
(0.0763)
|
-0.615
(0.0858)
|
-0.613
(0.0718)
|
| Week 24 |
-0.82
(0.0913)
|
-0.665
(0.0682)
|
-0.876
(0.0802)
|
-0.772
(0.0926)
|
-0.662
(0.0798)
|
| Title | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 |
|---|---|
| Description | The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. |
| Time Frame | from baseline till Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population; "Number Analyzed" reflect the number of non-missing, non-imputed observations at that specific timepoint. |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
7.372
(0.9136)
|
7.100
(0.7477)
|
6.534
(0.8878)
|
7.778
(0.994)
|
5.413
(0.7813)
|
| Week 24 |
10.412
(1.0642)
|
8.725
(0.9194)
|
8.835
(1.009)
|
10.762
(1.1497)
|
7.255
(0.9483)
|
| Title | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 |
|---|---|
| Description | The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. |
| Time Frame | from baseline till Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population; "Number Analyzed" reflect the number of non-missing, non-imputed observations at that specific timepoint. |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
9.096
(1.4966)
|
7.249
(1.1237)
|
9.749
(1.4177)
|
5.686
(1.6485)
|
5.569
(1.6467)
|
| Week 24 |
9.857
(1.5326)
|
7.962
(1.3932)
|
11.739
(1.4159)
|
8.981
(1.6876)
|
6.198
(1.696)
|
| Title | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 |
|---|---|
| Description | The FACIT Measurement System is a collection of health-related quality of life questionnaires that assess multidimensional health status in people with various chronic illnesses. The FACIT Fatigue Scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue. |
| Time Frame | from baseline till Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population; "Number Analyzed" reflect the number of non-missing, non-imputed observations at that specific timepoint. |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Week 12 |
11.014
(1.3593)
|
8.63
(1.0465)
|
10.884
(1.5424)
|
9.389
(1.3706)
|
6.381
(1.2026)
|
| Week 24 |
12.446
(1.5687)
|
10.439
(1.2157)
|
13.374
(1.5621)
|
12.381
(1.5193)
|
6.712
(1.4651)
|
| Title | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 |
|---|---|
| Description | 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. |
| Time Frame | at Week 12 and Week 24 visits |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX |
|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 |
| Week 12 |
0.163
(3.7)
|
1.79
(3.08)
|
19.9
(1.56)
|
32.1
(1.43)
|
| Week 24 |
0.122
(2.56)
|
1.64
(3.11)
|
20.9
(1.5)
|
35.2
(1.37)
|
| Title | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 |
|---|---|
| Description | Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ). |
| Time Frame | from baseline till Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population; "Number Analyzed" reflect the number of subjects with data available at that specific timepoint. |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Baseline |
26.9
(0.995)
|
29.2
(1.04)
|
27.7
(0.78)
|
28.9
(1.05)
|
28.9
(1.1)
|
| Week 12 |
166
(16.7)
|
420
(21)
|
519
(16.8)
|
488
(16.8)
|
52.9
(14.1)
|
| Week 24 |
150
(12.9)
|
422
(17.8)
|
484
(16.3)
|
487
(14.3)
|
35.4
(6.6)
|
| Title | Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response |
|---|---|
| Description | |
| Time Frame | from baseline till follow-up (FU) (i.e., 12 weeks after last study drug dosing at Week 22 or after early treatment discontinuation) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX | ALX-0061 Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). | All participants who received ALX-0061 |
| Measure Participants | 69 | 70 | 68 | 69 | 69 | 276 |
| Count of Participants [Participants] |
9
13%
|
16
22.9%
|
31
45.6%
|
33
47.8%
|
13
18.8%
|
89
25.8%
|
| Title | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Mild |
21
30.4%
|
28
40%
|
23
33.8%
|
20
29%
|
20
29%
|
| Moderate |
15
21.7%
|
12
17.1%
|
19
27.9%
|
20
29%
|
14
20.3%
|
| Severe |
6
8.7%
|
4
5.7%
|
2
2.9%
|
4
5.8%
|
2
2.9%
|
| Title | Number of Treatment-emergent Adverse Events by Severity |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Mild |
66
|
78
|
66
|
56
|
49
|
| Moderate |
34
|
24
|
26
|
40
|
22
|
| Severe |
6
|
5
|
4
|
5
|
2
|
| Title | Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Count of Participants [Participants] |
26
37.7%
|
25
35.7%
|
26
38.2%
|
25
36.2%
|
18
26.1%
|
| Title | Number of Treatment-related Treatment-emergent Adverse Events |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX |
|---|---|---|---|---|---|
| Arm/Group Description | 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 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 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 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 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). |
| Measure Participants | 69 | 70 | 68 | 69 | 69 |
| Number [Adverse events] |
55
|
52
|
46
|
47
|
21
|
Adverse Events
| Time Frame | 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). | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX | |||||
| Arm/Group Description | 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 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 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 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 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). | |||||
All Cause Mortality |
||||||||||
| ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/69 (1.4%) | 0/70 (0%) | 0/68 (0%) | 0/69 (0%) | 0/69 (0%) | |||||
Serious Adverse Events |
||||||||||
| ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/69 (7.2%) | 5/70 (7.1%) | 0/68 (0%) | 2/69 (2.9%) | 4/69 (5.8%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Cytopenia | 0/69 (0%) | 0 | 1/70 (1.4%) | 1 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Cardiac disorders | ||||||||||
| Cardiac arrest | 1/69 (1.4%) | 1 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Gastritis | 1/69 (1.4%) | 1 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Large intestine perforation | 0/69 (0%) | 0 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 1/69 (1.4%) | 1 | 0/69 (0%) | 0 |
| Infections and infestations | ||||||||||
| Arthritis bacterial | 0/69 (0%) | 0 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 1/69 (1.4%) | 1 | 0/69 (0%) | 0 |
| Cellulitis | 0/69 (0%) | 0 | 1/70 (1.4%) | 1 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Ear infection | 1/69 (1.4%) | 1 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Herpes Zoster | 0/69 (0%) | 0 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 1/69 (1.4%) | 1 |
| Pneumonia | 0/69 (0%) | 0 | 2/70 (2.9%) | 2 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 1/69 (1.4%) | 1 |
| Sepsis | 0/69 (0%) | 0 | 1/70 (1.4%) | 1 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Pharyngitis | 0/69 (0%) | 0 | 1/70 (1.4%) | 1 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Staphylococcal sepsis | 0/69 (0%) | 0 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 1/69 (1.4%) | 1 | 0/69 (0%) | 0 |
| Intervertebral discitis | 0/69 (0%) | 0 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 1/69 (1.4%) | 1 | 0/69 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Tendon rupture | 0/69 (0%) | 0 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 2/69 (2.9%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Rheumatoid arthritis | 0/69 (0%) | 0 | 1/70 (1.4%) | 1 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Ovarian adenoma | 1/69 (1.4%) | 1 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Angioedema | 1/69 (1.4%) | 1 | 0/70 (0%) | 0 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||
| ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 29/69 (42%) | 34/70 (48.6%) | 27/68 (39.7%) | 38/69 (55.1%) | 17/69 (24.6%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Neutropenia | 4/69 (5.8%) | 7 | 2/70 (2.9%) | 2 | 0/68 (0%) | 0 | 0/69 (0%) | 0 | 0/69 (0%) | 0 |
| General disorders | ||||||||||
| Injection site erythema | 4/69 (5.8%) | 5 | 5/70 (7.1%) | 7 | 7/68 (10.3%) | 8 | 3/69 (4.3%) | 3 | 0/69 (0%) | 0 |
| Infections and infestations | ||||||||||
| Bronchitis | 6/69 (8.7%) | 7 | 2/70 (2.9%) | 2 | 3/68 (4.4%) | 3 | 3/69 (4.3%) | 3 | 3/69 (4.3%) | 3 |
| Nasopharyngitis | 4/69 (5.8%) | 4 | 5/70 (7.1%) | 5 | 2/68 (2.9%) | 2 | 4/69 (5.8%) | 4 | 6/69 (8.7%) | 6 |
| Pharyngitis | 2/69 (2.9%) | 2 | 6/70 (8.6%) | 6 | 3/68 (4.4%) | 4 | 1/69 (1.4%) | 1 | 0/69 (0%) | 0 |
| Upper respiratory tract infection | 0/69 (0%) | 0 | 1/70 (1.4%) | 1 | 2/68 (2.9%) | 2 | 7/69 (10.1%) | 7 | 3/69 (4.3%) | 3 |
| Investigations | ||||||||||
| Alanine aminotransferase increased | 2/69 (2.9%) | 3 | 2/70 (2.9%) | 2 | 2/68 (2.9%) | 2 | 6/69 (8.7%) | 7 | 0/69 (0%) | 0 |
| Aspartate aminotransferase increased | 2/69 (2.9%) | 2 | 2/70 (2.9%) | 2 | 1/68 (1.5%) | 1 | 5/69 (7.2%) | 6 | 0/69 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Hypercholesterolaemia | 2/69 (2.9%) | 2 | 7/70 (10%) | 7 | 4/68 (5.9%) | 6 | 5/69 (7.2%) | 6 | 4/69 (5.8%) | 4 |
| Vascular disorders | ||||||||||
| Hypertension | 3/69 (4.3%) | 3 | 2/70 (2.9%) | 2 | 3/68 (4.4%) | 3 | 4/69 (5.8%) | 5 | 1/69 (1.4%) | 1 |
Limitations/Caveats
None reported
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Publication of any results from this study will be according to the principles of the Declaration of Helsinki, and will require prior review and written agreement of the Sponsor.
Results Point of Contact
| Name/Title | Medical Monitor |
|---|---|
| Organization | Ablynx NV |
| Phone | +32 (0)9 262 00 00 |
| clinicaltrials@ablynx.com |
Responsible Party:
Ablynx
ClinicalTrials.gov Identifier:
NCT02309359
Other Study ID Numbers:
- ALX0061-C201
- 2014-003033-26
First Posted:
Dec 5, 2014
Last Update Posted:
Aug 21, 2019
Last Verified:
Aug 1, 2019