Trial Outcomes & Findings for MSB11022 in Moderate to Severe Rheumatoid Arthritis (NCT NCT03052322)
NCT ID: NCT03052322
Last Updated: 2019-12-20
Results Overview
Adverse event (AE) was defined as any untoward medical occurrence in participants, which does not necessarily have causal relationship with treatment. Term Treatment-emergent Adverse Events (TEAE) is defined as AEs starting/worsening after first intake of the study drug. Hypersensitivity was the pre-defined TEAE of special Interest for this study. The percentage of participants with treatment emergent AESIs (hypersensitivity) were reported.
COMPLETED
PHASE3
288 participants
Up to Week 52
2019-12-20
Participant Flow
Participants were randomized in 1:1 ratio to receive either MSB11022 or EU-Humira for 48 weeks.
Participant milestones
| Measure |
MSB11022
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Overall Study
STARTED
|
143
|
145
|
|
Overall Study
COMPLETED
|
122
|
113
|
|
Overall Study
NOT COMPLETED
|
21
|
32
|
Reasons for withdrawal
| Measure |
MSB11022
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Overall Study
Other un-specified
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
10
|
9
|
|
Overall Study
Death
|
0
|
2
|
|
Overall Study
Lack of Efficacy
|
1
|
2
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
4
|
|
Overall Study
Adverse Event
|
6
|
13
|
Baseline Characteristics
MSB11022 in Moderate to Severe Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
Total
n=288 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.9 Years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
54.0 Years
STANDARD_DEVIATION 11.0 • n=7 Participants
|
53.9 Years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
108 Participants
n=5 Participants
|
119 Participants
n=7 Participants
|
227 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
140 Participants
n=5 Participants
|
144 Participants
n=7 Participants
|
284 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
142 Participants
n=5 Participants
|
143 Participants
n=7 Participants
|
285 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment.
Adverse event (AE) was defined as any untoward medical occurrence in participants, which does not necessarily have causal relationship with treatment. Term Treatment-emergent Adverse Events (TEAE) is defined as AEs starting/worsening after first intake of the study drug. Hypersensitivity was the pre-defined TEAE of special Interest for this study. The percentage of participants with treatment emergent AESIs (hypersensitivity) were reported.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)
|
4.2 Percentage of Participants
Interval 1.6 to 8.9
|
5.5 Percentage of Participants
Interval 2.4 to 10.6
|
SECONDARY outcome
Timeframe: Week 12Population: Intent-To-Treat (ITT) Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: participant's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), participant's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Outcome measures
| Measure |
MSB11022
n=142 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=141 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 12
|
79.6 Percentage of Participants
Interval 72.0 to 85.9
|
80.9 Percentage of Participants
Interval 73.4 to 86.9
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 4, 12, 24, 36 and 52Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment. Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Percentage of participants with positive anti-Drug antibodies (ADAs) status to Adalimumab were reported.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Week 52
|
60.8 Percentage of Participants
|
62.2 Percentage of Participants
|
|
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Baseline
|
7.7 Percentage of Participants
|
4.2 Percentage of Participants
|
|
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Week 2
|
20.3 Percentage of Participants
|
15.2 Percentage of Participants
|
|
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Week 4
|
29.8 Percentage of Participants
|
21.3 Percentage of Participants
|
|
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Week 12
|
54.2 Percentage of Participants
|
48.6 Percentage of Participants
|
|
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Week 24
|
71.9 Percentage of Participants
|
61.7 Percentage of Participants
|
|
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Week 36
|
66.9 Percentage of Participants
|
65.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 4, 12, 24, 36 and 52Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment. Here "Number of participants analyzed" signifies those who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at specified time points.
Titer was defined as the degree to which the antibody-serum sample could be diluted and still contained detectable amounts of antibody. Anti-Drug Antibodies (ADAs) titers for adalimumab was reported. Data was collected using validated bioanalytical method.
Outcome measures
| Measure |
MSB11022
n=115 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=104 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Week 4
|
6.0 Titer
Interval 1.0 to 16384.0
|
6.0 Titer
Interval 1.0 to 512.0
|
|
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Week 12
|
16.0 Titer
Interval 1.0 to 4096.0
|
16.0 Titer
Interval 1.0 to 16384.0
|
|
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Baseline
|
4.0 Titer
Interval 1.0 to 512.0
|
1.5 Titer
Interval 1.0 to 8.0
|
|
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Week 2
|
4.0 Titer
Interval 1.0 to 32768.0
|
12.0 Titer
Interval 1.0 to 1024.0
|
|
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Week 24
|
16.0 Titer
Interval 1.0 to 32768.0
|
24.0 Titer
Interval 1.0 to 131072.0
|
|
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Week 36
|
16.0 Titer
Interval 1.0 to 32768.0
|
16.0 Titer
Interval 1.0 to 131072.0
|
|
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Week 52
|
16.0 Titer
Interval 1.0 to 16384.0
|
12.0 Titer
Interval 1.0 to 32768.0
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 4, 12, 24, 36 and 52Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment. Here "Number of participants analyzed" signifies those who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at specified time points.
Percentage of participants with confirmed neutralizing antibodies status to Adalimumab were reported.
Outcome measures
| Measure |
MSB11022
n=115 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=104 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Week 36
|
24.1 Percentage of Participants
|
29.1 Percentage of Participants
|
|
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Week 52
|
32.9 Percentage of Participants
|
39.2 Percentage of Participants
|
|
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Baseline
|
45.5 Percentage of Participants
|
50.0 Percentage of Participants
|
|
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Week 2
|
31.0 Percentage of Participants
|
40.9 Percentage of Participants
|
|
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Week 4
|
33.3 Percentage of Participants
|
30.0 Percentage of Participants
|
|
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Week 12
|
33.8 Percentage of Participants
|
38.2 Percentage of Participants
|
|
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Week 24
|
27.0 Percentage of Participants
|
29.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 2, 4, 8, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52
Week 2
|
30.0 Percentage of Participants
Interval 22.55 to 38.32
|
29.7 Percentage of Participants
Interval 22.36 to 37.8
|
|
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52
Week 4
|
52.1 Percentage of Participants
Interval 43.58 to 60.56
|
52.8 Percentage of Participants
Interval 44.29 to 61.15
|
|
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52
Week 8
|
71.1 Percentage of Participants
Interval 62.93 to 78.42
|
72.9 Percentage of Participants
Interval 64.89 to 79.98
|
|
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52
Week 24
|
88.5 Percentage of Participants
Interval 81.98 to 93.28
|
83.3 Percentage of Participants
Interval 75.86 to 89.25
|
|
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52
Week 52
|
81.8 Percentage of Participants
Interval 73.78 to 88.24
|
86.4 Percentage of Participants
Interval 78.92 to 92.05
|
SECONDARY outcome
Timeframe: Week 2, 4, 8, 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
The ACR 50 Response is defined as greater than or equal to (\>=) 50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=50 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
Week 12
|
54.2 Percentage of Participants
Interval 45.7 to 62.6
|
51.1 Percentage of Participants
Interval 42.5 to 59.6
|
|
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
Week 24
|
65.5 Percentage of Participants
Interval 56.9 to 73.3
|
60.6 Percentage of Participants
Interval 51.7 to 68.9
|
|
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
Week 52
|
64.5 Percentage of Participants
Interval 55.3 to 72.9
|
66.1 Percentage of Participants
Interval 56.8 to 74.6
|
|
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
Week 2
|
6.4 Percentage of Participants
Interval 2.9 to 11.9
|
6.2 Percentage of Participants
Interval 2.9 to 11.5
|
|
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
Week 4
|
17.6 Percentage of Participants
Interval 11.7 to 24.9
|
19.4 Percentage of Participants
Interval 13.3 to 26.9
|
|
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
Week 8
|
40.8 Percentage of Participants
Interval 32.7 to 49.4
|
34.7 Percentage of Participants
Interval 26.9 to 43.1
|
SECONDARY outcome
Timeframe: Week 2, 4, 8, 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
The ACR 70 Response is defined as greater than or equal to (\>=) 70 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=70 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
Week 2
|
0.7 Percentage of Participants
Interval 0.0 to 3.9
|
0.7 Percentage of Participants
Interval 0.0 to 3.8
|
|
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
Week 4
|
4.9 Percentage of Participants
Interval 2.0 to 9.9
|
2.8 Percentage of Participants
Interval 0.8 to 6.9
|
|
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
Week 8
|
14.8 Percentage of Participants
Interval 9.4 to 21.7
|
12.5 Percentage of Participants
Interval 7.6 to 19.0
|
|
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
Week 12
|
26.8 Percentage of Participants
Interval 19.7 to 34.8
|
19.9 Percentage of Participants
Interval 13.6 to 27.4
|
|
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
Week 24
|
33.8 Percentage of Participants
Interval 26.0 to 42.3
|
35.6 Percentage of Participants
Interval 27.5 to 44.4
|
|
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
Week 52
|
39.7 Percentage of Participants
Interval 30.9 to 48.9
|
42.4 Percentage of Participants
Interval 33.3 to 51.8
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 4, 8, 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
DAS calculated on 28 joints is composite score derived from 4 measures: number of swollen joints (out of 28), number of tender joints (out of 28), Erythrocyte sedimentation rate (ESR), Patient's Global Assessment of Disease Activity on visual analog scale (VAS). Overall disease activity score DAS28 was derived using following formulas from DAS28:DAS28=0.56\*√(TJC28)+0.28\*√(SJC28) + 0.014\*GH+0.70\*ln(ESR). Where: TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, ln(ESR) = natural log of ESR, GH = general health component of DAS (ie, Patient's Global Assessment of Disease Activity, assessed using scale of 1-100 where 100 is maximal activity); For analyses, GH divided by 10 \& converted to 0.5 scale, i.e, 0, 0.5, 1, 1.5. DAS28-ESR of \>5.1 implies active disease, \<3.2 low disease activity, \& \<2.6 remission. Change of 1.2(twice measurement error)=significant change of disease activity state. Overall score ranges from 0-10 where higher score means more severe disease.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Change From Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 2
|
-0.9 Units on a scale
Standard Deviation 0.9
|
-0.7 Units on a scale
Standard Deviation 0.9
|
|
Change From Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 4
|
-1.4 Units on a scale
Standard Deviation 1.1
|
-1.2 Units on a scale
Standard Deviation 1.0
|
|
Change From Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 8
|
-1.9 Units on a scale
Standard Deviation 0.9
|
-1.7 Units on a scale
Standard Deviation 1.1
|
|
Change From Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 12
|
-2.4 Units on a scale
Standard Deviation 1.1
|
-2.1 Units on a scale
Standard Deviation 1.2
|
|
Change From Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 24
|
-2.7 Units on a scale
Standard Deviation 1.0
|
-2.3 Units on a scale
Standard Deviation 1.2
|
|
Change From Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 52
|
-2.8 Units on a scale
Standard Deviation 1.1
|
-2.5 Units on a scale
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: Week 2, 4, 8, 12, 24, and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Disease Activity Score calculated on 28 joints is composite score derived from 4 measures: number of swollen joints (out of 28), -number of tender joints (out of 28), -Erythrocyte sedimentation rate (ESR), -Patient's Global Assessment of Disease Activity on visual analog scale (VAS). Overall disease activity score DAS28 was derived using following formulas from DAS28: DAS28=0.56\*√(TJC28)+0.28\*√(SJC28) + 0.014\*GH+0.70\*ln(ESR). Where: -TJC28 = 28 joint count for tenderness, -SJC28 = 28 joint count for swelling, -ln(ESR) = natural logarithm of ESR, -GH = general health component of DAS (ie, Patient's Global Assessment of Disease Activity, assessed using scale of 1 to 100 where 100 is maximal activity); For analyses, GH was divided by 10 and converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5. DAS28-ESR of \>5.1 implies active disease, \<3.2 low disease activity, and \<2.6 remission.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Low Disease Activity: Week 2
|
10.0 Percentage of Participants
Interval 5.6 to 16.2
|
8.3 Percentage of Participants
Interval 4.4 to 14.0
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Low Disease Activity: Week 4
|
20.6 Percentage of Participants
Interval 14.2 to 28.2
|
16.0 Percentage of Participants
Interval 10.4 to 23.0
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Low Disease Activity: Week 8
|
33.1 Percentage of Participants
Interval 25.4 to 41.5
|
33.3 Percentage of Participants
Interval 25.7 to 41.7
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Low Disease Activity: Week 12
|
46.5 Percentage of Participants
Interval 38.1 to 55.0
|
42.6 Percentage of Participants
Interval 34.3 to 51.2
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Low Disease Activity: Week 24
|
55.1 Percentage of Participants
Interval 46.4 to 63.5
|
53.8 Percentage of Participants
Interval 44.9 to 62.5
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Low Disease Activity: Week 52
|
57.0 Percentage of Participants
Interval 47.7 to 65.9
|
56.8 Percentage of Participants
Interval 47.3 to 65.9
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Remission: Week 2
|
3.6 Percentage of Participants
Interval 1.2 to 8.1
|
2.1 Percentage of Participants
Interval 0.4 to 5.9
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Remission: Week 4
|
7.8 Percentage of Participants
Interval 3.9 to 13.5
|
6.9 Percentage of Participants
Interval 3.4 to 12.4
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Remission: Week 8
|
18.3 Percentage of Participants
Interval 12.3 to 25.7
|
16.0 Percentage of Participants
Interval 10.4 to 23.0
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Remission: Week 12
|
29.6 Percentage of Participants
Interval 22.2 to 37.8
|
24.1 Percentage of Participants
Interval 17.3 to 32.0
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Remission: Week 24
|
31.2 Percentage of Participants
Interval 23.6 to 39.6
|
34.1 Percentage of Participants
Interval 26.0 to 42.8
|
|
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Remission: Week 52
|
40.5 Percentage of Participants
Interval 31.7 to 49.8
|
36.4 Percentage of Participants
Interval 27.8 to 45.8
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 4, 8, 12, 24, and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
SDAI is numerical sum of 5 outcome parameters: tender \& swollen joint count (based on 28-joint assessment), Patient's \& Physician's Global Assessment of Disease Activity (VAS) \& level of C-reactive protein (CRP)(milligram per deciliter (mg/dL), normal\<1 mg/dL). SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28)+GH+PGA+CRP Where: -GH =general health component of DAS (i.e. Patient's Global Assessment of Disease Activity, assessed using scale of 1 to 100 where 100 is maximal activity; For analyses, GH was divided by 10 \& converted to 0.5 scale (0, 0.5, 1, 1.5).-PGA = Physician's Global Assessment of Disease Activity assessed using scale of 1 to 100 where 100 is maximal activity. For analyses, PGA will be divided by 10 \& converted to 0.5 scale (0, 0.5, 1, 1.5). where \[0-0.25\] = 0, \[0.25-0.75\] = 0.5, \[0.76-1.25\] = 1, etc. The total score range is 0-86 \& lower score indicates less disease activity.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Change From Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
Change at Week 2
|
-11.5 Units on a scale
Standard Deviation 10.6
|
-9.1 Units on a scale
Standard Deviation 10.0
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
Change at Week 4
|
-18.0 Units on a scale
Standard Deviation 11.3
|
-16.0 Units on a scale
Standard Deviation 10.9
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
Change at Week 8
|
-24.0 Units on a scale
Standard Deviation 10.6
|
-21.4 Units on a scale
Standard Deviation 11.0
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
Change at Week 12
|
-27.9 Units on a scale
Standard Deviation 10.8
|
-24.7 Units on a scale
Standard Deviation 10.9
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
Change at Week 24
|
-31.4 Units on a scale
Standard Deviation 11.2
|
-27.8 Units on a scale
Standard Deviation 10.6
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
Change at Week 52
|
-31.5 Units on a scale
Standard Deviation 11.6
|
-29.1 Units on a scale
Standard Deviation 10.8
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 4, 8, 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Clinical Disease Activity Index (CDAI) is a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA. Where, -GH = general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity, assessed using a scale of 1 to 100 where 100 is maximal activity; for analyses, GH was divided by 10 and converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5 etc. where \[0-0.25\] = 0, \[0.25-0.75\] = 0.5, \[0.76-1.25\] = 1, etc.). -PGA = Physician's Global Assessment of Disease Activity assessed using a scale of 1 to 100 where 100 is maximal activity. For analyses, PGA was divided by 10 and converted to a 0.5 scale, ie, 0, 0.5, 1, 1.5 etc. where \[0-0.25\] = 0, \[0.25-0.75\] = 0.5, \[0.76-1.25\] = 1, etc. The CDAI ranges from 0 to 76. Lower score indicates less disease activity.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 2
|
-10.8 Units on a scale
Standard Deviation 10.3
|
-8.5 Units on a scale
Standard Deviation 9.9
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 4
|
-17.4 Units on a scale
Standard Deviation 11.2
|
-15.2 Units on a scale
Standard Deviation 10.7
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 8
|
-23.5 Units on a scale
Standard Deviation 10.6
|
-20.6 Units on a scale
Standard Deviation 10.9
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 12
|
-27.4 Units on a scale
Standard Deviation 10.5
|
-24.1 Units on a scale
Standard Deviation 10.7
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 24
|
-30.8 Units on a scale
Standard Deviation 10.9
|
-27.1 Units on a scale
Standard Deviation 10.7
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
Change at Week 52
|
-31.1 Units on a scale
Standard Deviation 11.2
|
-28.5 Units on a scale
Standard Deviation 10.6
|
SECONDARY outcome
Timeframe: Week 2, 4, 8, 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
According to Boolean-based definition of remission of ACR/EULAR, a participant must satisfy all of the following: tender joint count \<= 1, swollen joint count \<= 1, CRP \<= 1 mg/dL, and Patient's Global Assessment of Disease Activity \<= 1 (0 to 10 VAS). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
Week 2
|
0.7 Percentage of Participants
Interval 0.0 to 3.9
|
0.0 Percentage of Participants
Interval 0.0 to 2.5
|
|
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
Week 4
|
0.7 Percentage of Participants
Interval 0.0 to 3.9
|
1.4 Percentage of Participants
Interval 0.2 to 5.1
|
|
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
Week 8
|
3.5 Percentage of Participants
Interval 1.2 to 8.0
|
4.2 Percentage of Participants
Interval 1.5 to 8.9
|
|
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
Week 12
|
5.7 Percentage of Participants
Interval 2.5 to 10.9
|
12.1 Percentage of Participants
Interval 7.2 to 18.6
|
|
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
Week 24
|
11.7 Percentage of Participants
Interval 6.8 to 18.3
|
8.4 Percentage of Participants
Interval 4.3 to 14.5
|
|
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
Week 52
|
21.0 Percentage of Participants
Interval 14.1 to 29.4
|
13.6 Percentage of Participants
Interval 7.9 to 21.1
|
SECONDARY outcome
Timeframe: Baseline up to Week 69Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment.
Adverse event(AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. All abnormal physical examinations occurring during the study have been reported as Adverse events. TEAEs included both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
TEAEs
|
58.0 Percentage of Participants
|
64.1 Percentage of Participants
|
|
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
Serious TEAEs
|
4.9 Percentage of Participants
|
9.7 Percentage of Participants
|
|
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
TEAEs Leading to Death
|
0 Percentage of Participants
|
0.7 Percentage of Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment.
Vital signs including body temperature, respiratory rate, and heart rate (after 5-minute rest) were measured. Percentage of participants with clinically meaningful abnormalities in vital signs were reported. Clinical meaningful was determined by the investigator.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Clinically Meaningful Differences in Vital Signs
|
0 Percentage of Participants
|
0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment.
Laboratory parameters including hematology, urinalysis, and biochemistry analysis were analyzed.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Clinically Meaningful Differences in Laboratory Values
|
0 Percentage of Participants
|
0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 12, 24, and 52Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment. Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Percentage of participants with clinically significant abnormal values for 12-lead electrocardiogram (ECG) at week 12, 24, and 52 were reported.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Clinically Significant Abnormal Values for 12-lead Electrocardiogram (ECG) at Week 12, 24, and 52
Week 24
|
0 Percentage of Participants
|
1.5 Percentage of Participants
|
|
Percentage of Participants With Clinically Significant Abnormal Values for 12-lead Electrocardiogram (ECG) at Week 12, 24, and 52
Week 52
|
0 Percentage of Participants
|
0.8 Percentage of Participants
|
|
Percentage of Participants With Clinically Significant Abnormal Values for 12-lead Electrocardiogram (ECG) at Week 12, 24, and 52
Week 12
|
0 Percentage of Participants
|
0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24 and 52Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment.
For ANA, positivity is defined as any participant with ANA titer greater than (\>) 1:160 and negativity is defined as ANA titer less than (\<) 1:160. For anti-ds DNA, positivity is defined as any participant with adsDNA \> 15 units per milliliter (U/mL), intermediate category is defined as value between 10 U/mL to 15 U/mL and negativity is defined as adsDNA \< 10 U/mL. Percentage of participants with anti-nuclear antibody (ANA) and anti double-stranded deoxyribonucleic acid (Anti-dsDNA) at baseline, week 24 and 52 were reported.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 52: Anti-dsDNA: Negative
|
95.0 Percentage of Participants
|
97.5 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 52: Anti-dsDNA: Intermediate
|
0.8 Percentage of Participants
|
1.7 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 52: Anti-dsDNA: Positive
|
4.1 Percentage of Participants
|
0.8 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 24: ANA: Negative
|
92.0 Percentage of Participants
|
91.6 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 24: ANA: Positive
|
8.0 Percentage of Participants
|
8.4 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 52: ANA: Negative
|
78.8 Percentage of Participants
|
84.7 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 52: ANA: Positive
|
21.2 Percentage of Participants
|
15.3 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Baseline: Anti-dsDNA: Negative
|
97.9 Percentage of Participants
|
98.6 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Baseline: Anti-dsDNA: Intermediate
|
1.4 Percentage of Participants
|
0.7 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Baseline: Anti-dsDNA: Positive
|
0.7 Percentage of Participants
|
0.7 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 24: Anti-dsDNA: Negative
|
95.7 Percentage of Participants
|
96.2 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 24: Anti-dsDNA: Intermediate
|
2.2 Percentage of Participants
|
3.0 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Week 24: Anti-dsDNA: Positive
|
2.2 Percentage of Participants
|
0.8 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Baseline: ANA: Negative
|
97.2 Percentage of Participants
|
95.1 Percentage of Participants
|
|
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Baseline: ANA: Positive
|
2.8 Percentage of Participants
|
4.9 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
The HAQ-DI is a participant-reported questionnaire that is commonly used in RA to measure disease associated disability (assessment of physical function). It consists of several questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. HAQ-DI scores range from 0 to 3. The disability section of the questionnaire scores the participant's self-perception on the degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do).
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 12, 24 and 52
Week 52
|
0.9 Units on a scale
Standard Deviation 0.7
|
0.9 Units on a scale
Standard Deviation 0.6
|
|
Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 12, 24 and 52
Baseline
|
1.6 Units on a scale
Standard Deviation 0.6
|
1.6 Units on a scale
Standard Deviation 0.6
|
|
Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 12, 24 and 52
Week 12
|
1.1 Units on a scale
Standard Deviation 0.6
|
1.1 Units on a scale
Standard Deviation 0.6
|
|
Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 12, 24 and 52
Week 24
|
1.0 Units on a scale
Standard Deviation 0.6
|
1.0 Units on a scale
Standard Deviation 0.6
|
SECONDARY outcome
Timeframe: Baseline, Week 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
The Short Form Health Survey (SF-36) is a validated 36-item, patient-reported indication of overall health status not specific to any age, disease or Treatment group. The SF-36 questionnaire contains 36 questions pertaining to eight subscales of health status. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) is based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning).
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
PCS: Baseline
|
30.3 Units on a scale
Standard Deviation 7.6
|
30.6 Units on a scale
Standard Deviation 7.8
|
|
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
PCS: Week 12
|
39.0 Units on a scale
Standard Deviation 7.9
|
38.6 Units on a scale
Standard Deviation 8.6
|
|
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
PCS: Week 24
|
40.5 Units on a scale
Standard Deviation 8.8
|
40.8 Units on a scale
Standard Deviation 9.1
|
|
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
PCS: Week 52
|
41.8 Units on a scale
Standard Deviation 9.5
|
41.6 Units on a scale
Standard Deviation 9.3
|
|
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
MCS: Baseline
|
40.9 Units on a scale
Standard Deviation 13.2
|
43.4 Units on a scale
Standard Deviation 11.7
|
|
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
MCS: Week 12
|
47.4 Units on a scale
Standard Deviation 11.3
|
48.2 Units on a scale
Standard Deviation 11.3
|
|
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
MCS: Week 24
|
49.8 Units on a scale
Standard Deviation 10.8
|
48.8 Units on a scale
Standard Deviation 10.9
|
|
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
MCS: Week 52
|
48.0 Units on a scale
Standard Deviation 10.4
|
49.3 Units on a scale
Standard Deviation 11.5
|
SECONDARY outcome
Timeframe: Baseline, Week 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L descriptive system provides a profile of the participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual based on the UK scoring algorithm.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Utility Index Score at Baseline, Week 12, 24 and 52
Baseline
|
0.6 Units on a scale
Standard Deviation 0.2
|
0.6 Units on a scale
Standard Deviation 0.2
|
|
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Utility Index Score at Baseline, Week 12, 24 and 52
Week 12
|
0.8 Units on a scale
Standard Deviation 0.1
|
0.8 Units on a scale
Standard Deviation 0.1
|
|
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Utility Index Score at Baseline, Week 12, 24 and 52
Week 24
|
0.8 Units on a scale
Standard Deviation 0.1
|
0.8 Units on a scale
Standard Deviation 0.1
|
|
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Utility Index Score at Baseline, Week 12, 24 and 52
Week 52
|
0.8 Units on a scale
Standard Deviation 0.2
|
0.8 Units on a scale
Standard Deviation 0.1
|
SECONDARY outcome
Timeframe: Baseline, Week 12, 24 and 52Population: ITT Analysis Set included all participants randomly allocated to a treatment, based on intent to treat "as randomized" principle (planned treatment regimen rather than actual treatment given in case of any difference). Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
EQ-5D-5L: Standardized, participant-rated questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L Visual Analog Scale. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. Responses to 5 dimension scores were combined and converted into single preference-weighted health utility index score 0 (worst health state) to 1 (better health state). EQ-VAS: Self-rated health status using a vertical VAS. EQ-VAS records participant's perceptions of their own current overall health in range from 0 (worst imaginable health) to 100 (best imaginable health).
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Baseline, Week 12, 24 and 52
Baseline
|
42.4 Units on a scale
Standard Deviation 18.5
|
45.4 Units on a scale
Standard Deviation 20.4
|
|
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Baseline, Week 12, 24 and 52
Week 12
|
64.6 Units on a scale
Standard Deviation 19.6
|
63.2 Units on a scale
Standard Deviation 20.9
|
|
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Baseline, Week 12, 24 and 52
Week 24
|
66.2 Units on a scale
Standard Deviation 22.2
|
65.6 Units on a scale
Standard Deviation 24.3
|
|
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Baseline, Week 12, 24 and 52
Week 52
|
68.8 Units on a scale
Standard Deviation 21.7
|
69.0 Units on a scale
Standard Deviation 22.7
|
SECONDARY outcome
Timeframe: Immediately, 15 minutes and 1 hour post-injection on Baseline (Week 4), Week 6 and 8Population: The Safety Analysis Set included all randomized participants who received at least one dose of study treatment. Here "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
The participant's reported perception of pain was measured on a VAS where the slash drawn by the participant represents pain of increasing intensity. VAS score ranges from 0-10 millimeter \[mm\], where; 0 mm=no pain and 10 mm=worst possible pain. The first 2 injections was administered by qualified personnel. The next three doses of IMP (3-5) will be self-administered by the participant and injection site pain was assessed. Pain was recorded immediately after, 15 minutes after, and 1 hour after the injections received by the participants.
Outcome measures
| Measure |
MSB11022
n=143 Participants
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 Participants
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
Change at Week 6: Immediately post-injection
|
-1.4 Millimeter (mm)
Standard Deviation 5.12
|
-1.3 Millimeter (mm)
Standard Deviation 10.16
|
|
Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
Change at Week 6: 15 min post-injection
|
-0.2 Millimeter (mm)
Standard Deviation 2.67
|
0.4 Millimeter (mm)
Standard Deviation 3.29
|
|
Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
Change at Week 6: 1 hour post-injection
|
0.0 Millimeter (mm)
Standard Deviation 0.66
|
0.0 Millimeter (mm)
Standard Deviation 2.67
|
|
Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
Change at Week 8: Immediately post-injection
|
-1.7 Millimeter (mm)
Standard Deviation 6.48
|
-2.3 Millimeter (mm)
Standard Deviation 10.35
|
|
Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
Change at Week 8: 15 min post-injection
|
-0.3 Millimeter (mm)
Standard Deviation 2.25
|
-0.7 Millimeter (mm)
Standard Deviation 4.12
|
|
Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
Change at Week 8: 1 hour post-injection
|
-0.1 Millimeter (mm)
Standard Deviation 0.57
|
-0.7 Millimeter (mm)
Standard Deviation 5.43
|
Adverse Events
MSB11022
EU-Humira
Serious adverse events
| Measure |
MSB11022
n=143 participants at risk
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 participants at risk
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Immune system disorders
Anaphylactic reaction
|
0.70%
1/143 • Up to Week 69
|
0.00%
0/145 • Up to Week 69
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Infections and infestations
Tracheobronchitis
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Investigations
Mycobacterium tuberculosis complex test positive
|
0.70%
1/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.70%
1/143 • Up to Week 69
|
1.4%
2/145 • Up to Week 69
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.70%
1/143 • Up to Week 69
|
1.4%
2/145 • Up to Week 69
|
|
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
|
0.70%
1/143 • Up to Week 69
|
0.00%
0/145 • Up to Week 69
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
0.70%
1/143 • Up to Week 69
|
0.00%
0/145 • Up to Week 69
|
|
Nervous system disorders
Transient global amnesia
|
0.70%
1/143 • Up to Week 69
|
0.00%
0/145 • Up to Week 69
|
|
Product Issues
Device dislocation
|
0.70%
1/143 • Up to Week 69
|
0.00%
0/145 • Up to Week 69
|
|
Respiratory, thoracic and mediastinal disorders
Rheumatoid lung
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
General disorders
Death
|
0.00%
0/143 • Up to Week 69
|
0.69%
1/145 • Up to Week 69
|
|
Infections and infestations
Arthritis bacterial
|
0.70%
1/143 • Up to Week 69
|
0.00%
0/145 • Up to Week 69
|
Other adverse events
| Measure |
MSB11022
n=143 participants at risk
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
|
EU-Humira
n=145 participants at risk
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
|
|---|---|---|
|
General disorders
Injection site erythema
|
2.8%
4/143 • Up to Week 69
|
8.3%
12/145 • Up to Week 69
|
|
General disorders
Injection site pain
|
1.4%
2/143 • Up to Week 69
|
6.9%
10/145 • Up to Week 69
|
|
General disorders
Injection site pruritus
|
0.70%
1/143 • Up to Week 69
|
5.5%
8/145 • Up to Week 69
|
|
Infections and infestations
Nasopharyngitis
|
4.2%
6/143 • Up to Week 69
|
9.0%
13/145 • Up to Week 69
|
|
Skin and subcutaneous tissue disorders
Erythema
|
1.4%
2/143 • Up to Week 69
|
5.5%
8/145 • Up to Week 69
|
Additional Information
Eugenia Kunina, senior clinical development manager
Fresenius Kabi Swiss BioSim GmbH
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER