Trial Outcomes & Findings for Phase IIb Study of Evobrutinib in Subjects With Rheumatoid Arthritis (NCT NCT03233230)
NCT ID: NCT03233230
Last Updated: 2020-09-28
Results Overview
ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants \* 100.
COMPLETED
PHASE2
390 participants
Week 12
2020-09-28
Participant Flow
A total of 933 participants with rheumatoid arthritis were screened. Out of which, 390 participants were randomized in ratio of 1:1:1:1 to 1 of the 4 treatment groups: Placebo; M2951 25 milligrams (mg) once daily (QD), M2951 75 mg QD and M2951 50 mg twice daily (BID).
Participant milestones
| Measure |
Placebo
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
97
|
98
|
96
|
99
|
|
Overall Study
COMPLETED
|
82
|
83
|
84
|
91
|
|
Overall Study
NOT COMPLETED
|
15
|
15
|
12
|
8
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
6
|
3
|
6
|
3
|
|
Overall Study
Protocol Violation
|
1
|
2
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
0
|
0
|
|
Overall Study
Other
|
5
|
5
|
5
|
3
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
3
|
0
|
0
|
Baseline Characteristics
Phase IIb Study of Evobrutinib in Subjects With Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
Total
n=390 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
52.9 years
STANDARD_DEVIATION 12.24 • n=5 Participants
|
50.9 years
STANDARD_DEVIATION 13.15 • n=7 Participants
|
53.3 years
STANDARD_DEVIATION 11.33 • n=5 Participants
|
53.7 years
STANDARD_DEVIATION 12.13 • n=4 Participants
|
52.7 years
STANDARD_DEVIATION 12.21 • n=21 Participants
|
|
Sex: Female, Male
Female
|
77 Participants
n=5 Participants
|
82 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
77 Participants
n=4 Participants
|
312 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
78 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
32 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
38 Participants
n=4 Participants
|
138 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
65 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
252 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
92 Participants
n=5 Participants
|
94 Participants
n=7 Participants
|
91 Participants
n=5 Participants
|
97 Participants
n=4 Participants
|
374 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of Investigational Medicinal Product (IMP) (M2951 or placebo).
ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants \* 100.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12
|
49.5 percentage of participants
|
59.2 percentage of participants
|
51.0 percentage of participants
|
59.6 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28) + 0.36\*natural log(hsCRP+1) + 0.014\* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. Percentage of participants with low DAS28 \< 3.2 based on DAS28- hsCRP at Week 12 were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
|
7.2 percentage of participants
|
20.4 percentage of participants
|
24.0 percentage of participants
|
20.2 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28) + 0.36\*natural log(hsCRP+1) + 0.014\* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. A DAS28 score less than (\<) 2.6 indicated clinical remission. Percentage of participants with low DAS28 \< 2.6 based on DAS28- hsCRP at Week 12 were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
|
1.0 percentage of participants
|
10.2 percentage of participants
|
10.4 percentage of participants
|
10.1 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
ACR50 response: a participant has at least 50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 50% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index \[HAQ-DI\]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein \[hsCRP\]. Percentage of participants with ACR50 response = Number of participants with ACR50 response divided by total mITT participants \* 100.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50)
|
19.6 percentage of participants
|
28.6 percentage of participants
|
27.1 percentage of participants
|
26.3 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
ACR70 response: a participant has at least 70% improvement ACR70 response in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 70% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index \[HAQ-DI\]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein \[hsCRP\]. Percentage of participants with ACR70 response = Number of participants with ACR70 response divided by total mITT participants \* 100.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70)
|
5.2 percentage of participants
|
11.2 percentage of participants
|
10.4 percentage of participants
|
10.1 percentage of participants
|
SECONDARY outcome
Timeframe: up to Week 16Population: The safety analysis set (SAF) included all participants who received at least 1 dose of IMP (M2951 or placebo).
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inparticipant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 16 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
TEAEs
|
44 Participants
|
48 Participants
|
48 Participants
|
50 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Serious TEAEs
|
2 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: up to Week 16Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).
Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Grade 1
|
33 Participants
|
42 Participants
|
37 Participants
|
40 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Grade 2
|
19 Participants
|
14 Participants
|
23 Participants
|
17 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Grade 3
|
2 Participants
|
5 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Grade 4
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Grade 5
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to Week 16Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).
Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to Week 16Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).
Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to Week 16Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 4, 8, 12 and 16Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Change in the serum levels of IgG, IgA, IgM were assessed.
Outcome measures
| Measure |
Placebo
n=95 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=96 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=95 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgG: Week 2
|
-0.02 gram per liter (g/L)
Standard Deviation 1.083
|
-0.07 gram per liter (g/L)
Standard Deviation 1.042
|
-0.21 gram per liter (g/L)
Standard Deviation 0.968
|
-0.09 gram per liter (g/L)
Standard Deviation 1.062
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgG: Week 4
|
-0.05 gram per liter (g/L)
Standard Deviation 1.465
|
-0.15 gram per liter (g/L)
Standard Deviation 1.576
|
-0.34 gram per liter (g/L)
Standard Deviation 1.254
|
-0.17 gram per liter (g/L)
Standard Deviation 1.168
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgG: Week 8
|
0.12 gram per liter (g/L)
Standard Deviation 1.513
|
-0.28 gram per liter (g/L)
Standard Deviation 2.052
|
-0.37 gram per liter (g/L)
Standard Deviation 1.565
|
-0.35 gram per liter (g/L)
Standard Deviation 2.037
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgG: Week 12
|
0.47 gram per liter (g/L)
Standard Deviation 1.617
|
-0.17 gram per liter (g/L)
Standard Deviation 2.080
|
-0.33 gram per liter (g/L)
Standard Deviation 1.493
|
-0.23 gram per liter (g/L)
Standard Deviation 1.781
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgG: Week 16
|
0.08 gram per liter (g/L)
Standard Deviation 1.829
|
-0.14 gram per liter (g/L)
Standard Deviation 2.349
|
-0.14 gram per liter (g/L)
Standard Deviation 1.808
|
0.06 gram per liter (g/L)
Standard Deviation 1.960
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgA: Week 2
|
-0.01 gram per liter (g/L)
Standard Deviation 0.253
|
-0.15 gram per liter (g/L)
Standard Deviation 1.187
|
0.00 gram per liter (g/L)
Standard Deviation 0.242
|
0.03 gram per liter (g/L)
Standard Deviation 0.369
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgA: Week 4
|
-0.05 gram per liter (g/L)
Standard Deviation 0.326
|
-0.01 gram per liter (g/L)
Standard Deviation 0.359
|
-0.05 gram per liter (g/L)
Standard Deviation 0.333
|
0.02 gram per liter (g/L)
Standard Deviation 0.396
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgA: Week 8
|
-0.02 gram per liter (g/L)
Standard Deviation 0.346
|
-0.16 gram per liter (g/L)
Standard Deviation 1.322
|
-0.06 gram per liter (g/L)
Standard Deviation 0.373
|
0.07 gram per liter (g/L)
Standard Deviation 0.567
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgA: Week 12
|
0.02 gram per liter (g/L)
Standard Deviation 0.373
|
0.01 gram per liter (g/L)
Standard Deviation 0.444
|
-0.08 gram per liter (g/L)
Standard Deviation 0.388
|
0.05 gram per liter (g/L)
Standard Deviation 0.545
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgA: Week 16
|
0.01 gram per liter (g/L)
Standard Deviation 0.466
|
0.07 gram per liter (g/L)
Standard Deviation 0.465
|
-0.11 gram per liter (g/L)
Standard Deviation 0.380
|
0.05 gram per liter (g/L)
Standard Deviation 0.478
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgM: Week 2
|
-0.04 gram per liter (g/L)
Standard Deviation 0.198
|
-0.04 gram per liter (g/L)
Standard Deviation 0.183
|
-0.03 gram per liter (g/L)
Standard Deviation 0.281
|
-0.01 gram per liter (g/L)
Standard Deviation 0.323
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgM: Week 4
|
-0.04 gram per liter (g/L)
Standard Deviation 0.199
|
-0.11 gram per liter (g/L)
Standard Deviation 0.224
|
-0.11 gram per liter (g/L)
Standard Deviation 0.217
|
-0.05 gram per liter (g/L)
Standard Deviation 0.385
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgM: Week 8
|
-0.03 gram per liter (g/L)
Standard Deviation 0.310
|
-0.20 gram per liter (g/L)
Standard Deviation 0.243
|
-0.23 gram per liter (g/L)
Standard Deviation 0.327
|
-0.10 gram per liter (g/L)
Standard Deviation 0.485
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgM: Week 12
|
-0.01 gram per liter (g/L)
Standard Deviation 0.265
|
-0.20 gram per liter (g/L)
Standard Deviation 0.309
|
-0.25 gram per liter (g/L)
Standard Deviation 0.296
|
-0.17 gram per liter (g/L)
Standard Deviation 0.406
|
|
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
IgM: Week 16
|
-0.16 gram per liter (g/L)
Standard Deviation 0.776
|
-0.12 gram per liter (g/L)
Standard Deviation 0.436
|
-0.22 gram per liter (g/L)
Standard Deviation 0.246
|
-0.12 gram per liter (g/L)
Standard Deviation 0.487
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 4, 8, 12 and 16Population: SAF included all participants who received at least 1 dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed specifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time point.
Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Outcome measures
| Measure |
Placebo
n=90 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=90 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=92 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=97 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16
Week 12
|
-22 cells per microliter (cells/microliter)
Standard Deviation 136.4
|
41 cells per microliter (cells/microliter)
Standard Deviation 111.8
|
51 cells per microliter (cells/microliter)
Standard Deviation 156.2
|
54 cells per microliter (cells/microliter)
Standard Deviation 145.0
|
|
Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16
Week 2
|
-13 cells per microliter (cells/microliter)
Standard Deviation 111.0
|
264 cells per microliter (cells/microliter)
Standard Deviation 1832.7
|
161 cells per microliter (cells/microliter)
Standard Deviation 648.3
|
74 cells per microliter (cells/microliter)
Standard Deviation 144.8
|
|
Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16
Week 4
|
-20 cells per microliter (cells/microliter)
Standard Deviation 115.7
|
71 cells per microliter (cells/microliter)
Standard Deviation 130.1
|
66 cells per microliter (cells/microliter)
Standard Deviation 145.3
|
93 cells per microliter (cells/microliter)
Standard Deviation 137.6
|
|
Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16
Week 8
|
-21 cells per microliter (cells/microliter)
Standard Deviation 87.5
|
35 cells per microliter (cells/microliter)
Standard Deviation 103.1
|
56 cells per microliter (cells/microliter)
Standard Deviation 188.1
|
59 cells per microliter (cells/microliter)
Standard Deviation 145.4
|
|
Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16
Week 16
|
-20 cells per microliter (cells/microliter)
Standard Deviation 121.9
|
-3 cells per microliter (cells/microliter)
Standard Deviation 108.5
|
-40 cells per microliter (cells/microliter)
Standard Deviation 133.5
|
-19 cells per microliter (cells/microliter)
Standard Deviation 235.6
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), C-reactive Protein (in milligrams per deciliter \[mg/dL\]), and participant's global assessment (visual analog scale \[VAS\]: 0 centimeter (cm) \[very well\] to 10 cm \[worst\], higher scores indicated worse health condition) and all scores were less than or equal to (\<=) 1. Percentage of participants with ACR-EULAR Boolean Remission were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12
|
0.0 percentage of participants
|
0.0 percentage of participants
|
1.0 percentage of participants
|
3.0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
CDAI: 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 + PhGA where, GH = general health component of the Disease Activity Score \[DAS\] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity). CDAI score =\< 2.8 indicated clinical remission. Percentage of participants with CDAI score =\< 2.8 were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=<] 2.8 at Week 12
|
1.0 percentage of participants
|
4.1 percentage of participants
|
6.3 percentage of participants
|
3.0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the Disease Activity Score \[DAS\] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity). SDAI score =\< 3.3 indicated clinical remission. Percentage of participants with SDAI score =\< 3.3 at Week 12 were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=<] 3.3 at Week 12
|
0.0 percentage of participants
|
3.1 percentage of participants
|
4.2 percentage of participants
|
3.0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. EULAR DAS28-CRP responder index: good (absolute: \<3.2 or \>1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: \>5.1 or \<0.6 improvement from baseline). Percentage of Participants With Good or Moderate EULAR Responses were reported.
Outcome measures
| Measure |
Placebo
n=97 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12
|
54.6 percentage of participants
|
65.3 percentage of participants
|
66.7 percentage of participants
|
71.7 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, disability index of the Health Assessment Questionnaire \[HAQ\], and C-reactive protein \[CRP\]) was calculated (a positive change indicated improvement, and the maximum worst change was limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement).
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP)
|
26.51 percent change
Standard Deviation 25.779
|
34.66 percent change
Standard Deviation 29.033
|
33.09 percent change
Standard Deviation 27.724
|
36.99 percent change
Standard Deviation 26.241
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
DAS28 was a composite score used for measuring disease activity in participants with rheumatoid arthritis. The calculation was based on the tender joint count (out of 28 joints), swollen joint count (out of 28 joints), hsCRP (milligrams per liter \[mg/L\]) and Participant's Global Assessment of Disease Activity. Total DAS28-hsCRP score ranged from 0 (none) to 9.4 (extreme disease activity). DAS28-hsCRP \< 3.2 implied low disease activity and \>= 3.2 to \<= 5.1 implied moderate disease activity, \> 5.1 implied high disease activity. DAS28-hsCRP = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(hsCRP in mg/L +1) + 0.014\* Participant's Global Assessment of Disease Activity + 0.96; ln = natural logarithm, sqrt = square root.
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
|
-1.21 units on a scale
Standard Deviation 1.048
|
-1.45 units on a scale
Standard Deviation 1.230
|
-1.62 units on a scale
Standard Deviation 1.257
|
-1.75 units on a scale
Standard Deviation 1.229
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The CDAI was 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 + PhGA where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity).
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12
|
-16.9 units on a scale
Standard Deviation 13.09
|
-18.0 units on a scale
Standard Deviation 13.00
|
-18.9 units on a scale
Standard Deviation 14.33
|
-20.3 units on a scale
Standard Deviation 13.90
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
SDAI was numerical sum of 5 outcome parameters: 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity).
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12
|
-17.000 units on a scale
Standard Deviation 13.5175
|
-18.647 units on a scale
Standard Deviation 13.5957
|
-19.404 units on a scale
Standard Deviation 14.1591
|
-21.053 units on a scale
Standard Deviation 14.3720
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12
TJC
|
-11 joints
Standard Deviation 12.0
|
-11 joints
Standard Deviation 10.6
|
-13 joints
Standard Deviation 13.2
|
-12 joints
Standard Deviation 10.8
|
|
Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12
SJC
|
-7 joints
Standard Deviation 7.5
|
-8 joints
Standard Deviation 6.1
|
-8 joints
Standard Deviation 7.7
|
-8 joints
Standard Deviation 6.6
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12
|
-20 millimeter (mm)
Standard Deviation 29.6
|
-19 millimeter (mm)
Standard Deviation 27.9
|
-17 millimeter (mm)
Standard Deviation 29.6
|
-25 millimeter (mm)
Standard Deviation 25.7
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=95 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12
|
-21 millimeter
Standard Deviation 24.7
|
-24 millimeter
Standard Deviation 26.9
|
-22 millimeter
Standard Deviation 24.7
|
-25 millimeter
Standard Deviation 26.6
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=95 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12
|
-0.38 units on a scale
Standard Deviation 0.567
|
-0.58 units on a scale
Standard Deviation 0.662
|
-0.40 units on a scale
Standard Deviation 0.658
|
-0.52 units on a scale
Standard Deviation 0.616
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12
|
-29 millimeter
Standard Deviation 21.2
|
-33 millimeter
Standard Deviation 26.5
|
-34 millimeter
Standard Deviation 26.1
|
-37 millimeter
Standard Deviation 25.3
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12
|
-1.11 milligram per liter (mg/L)
Standard Deviation 25.925
|
-6.42 milligram per liter (mg/L)
Standard Deviation 23.280
|
-5.45 milligram per liter (mg/L)
Standard Deviation 28.807
|
-7.69 milligram per liter (mg/L)
Standard Deviation 23.007
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12
SJC
|
-46 percent change
Standard Deviation 52.7
|
-53 percent change
Standard Deviation 42.6
|
-56 percent change
Standard Deviation 40.3
|
-58 percent change
Standard Deviation 43.8
|
|
Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12
TJC
|
-39 percent change
Standard Deviation 45.6
|
-46 percent change
Standard Deviation 44.2
|
-51 percent change
Standard Deviation 42.8
|
-49 percent change
Standard Deviation 37.5
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=96 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12
|
-13 percent change
Standard Deviation 111.0
|
-21 percent change
Standard Deviation 69.3
|
-13 percent change
Standard Deviation 65.7
|
-33 percent change
Standard Deviation 35.9
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=95 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12
|
-23 percent change
Standard Deviation 65.0
|
-32 percent change
Standard Deviation 38.4
|
-29 percent change
Standard Deviation 40.5
|
-32 percent change
Standard Deviation 48.4
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Outcome measures
| Measure |
Placebo
n=95 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=95 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12
|
-20.09 percent change
Standard Deviation 40.084
|
-31.85 percent change
Standard Deviation 37.124
|
-21.27 percent change
Standard Deviation 44.571
|
-27.12 percent change
Standard Deviation 42.624
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=98 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12
|
-42 percent change
Standard Deviation 31.4
|
-44 percent change
Standard Deviation 51.9
|
-47 percent change
Standard Deviation 34.9
|
-52 percent change
Standard Deviation 33.5
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.
Outcome measures
| Measure |
Placebo
n=96 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=97 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12
|
95.01 percent change
Standard Deviation 380.161
|
10.93 percent change
Standard Deviation 167.257
|
182.57 percent change
Standard Deviation 1775.154
|
-13.91 percent change
Standard Deviation 105.688
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The Magnetic Resonance Imaging (MRI) analysis set included all randomized participants who have at least at least 1 pre-dose and 1 post-dose MRI assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement.
Outcome measures
| Measure |
Placebo
n=44 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=49 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=47 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=51 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12
|
0 units on a scale
Standard Deviation 1.9
|
-1 units on a scale
Standard Deviation 2.5
|
-1 units on a scale
Standard Deviation 3.4
|
-1 units on a scale
Standard Deviation 2.4
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The MRI analysis set included all randomized participants who have at least at least 1 pre-dose and 1 post-dose MRI assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone.
Outcome measures
| Measure |
Placebo
n=44 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=49 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=47 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=51 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12
|
-1 units on a scale
Standard Deviation 5.8
|
0 units on a scale
Standard Deviation 4.6
|
0 units on a scale
Standard Deviation 5.4
|
0 units on a scale
Standard Deviation 4.0
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Quality of Life (QoL) Analysis Set: all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. "Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The HAQ-DI questionnaire assessed the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=93 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=86 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=92 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
|
-0.41 units on a scale
Standard Deviation 0.543
|
-0.61 units on a scale
Standard Deviation 0.637
|
-0.45 units on a scale
Standard Deviation 0.657
|
-0.53 units on a scale
Standard Deviation 0.631
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: QoL analysis set: all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was 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 |
Placebo
n=87 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=93 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=86 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=92 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12
PCS
|
5.9 units on a scale
Standard Deviation 7.10
|
7.1 units on a scale
Standard Deviation 8.50
|
6.4 units on a scale
Standard Deviation 8.50
|
7.1 units on a scale
Standard Deviation 8.28
|
|
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12
MCS
|
4.9 units on a scale
Standard Deviation 11.46
|
5.7 units on a scale
Standard Deviation 8.41
|
5.0 units on a scale
Standard Deviation 11.72
|
4.7 units on a scale
Standard Deviation 8.95
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: QoL analysis set included all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post Baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=93 Participants
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=86 Participants
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=92 Participants
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12
|
9 units on a scale
Standard Deviation 11.4
|
10 units on a scale
Standard Deviation 9.4
|
9 units on a scale
Standard Deviation 9.0
|
8 units on a scale
Standard Deviation 10.7
|
Adverse Events
Placebo
M2951 25 mg QD
M2951 75 mg QD
M2951 50 mg BID
Serious adverse events
| Measure |
Placebo
n=97 participants at risk
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 participants at risk
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 participants at risk
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 participants at risk
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.00%
0/97 • up to Week 16
|
0.00%
0/98 • up to Week 16
|
0.00%
0/96 • up to Week 16
|
1.0%
1/99 • up to Week 16
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/97 • up to Week 16
|
1.0%
1/98 • up to Week 16
|
0.00%
0/96 • up to Week 16
|
0.00%
0/99 • up to Week 16
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/97 • up to Week 16
|
0.00%
0/98 • up to Week 16
|
1.0%
1/96 • up to Week 16
|
0.00%
0/99 • up to Week 16
|
|
Infections and infestations
Sinusitis
|
0.00%
0/97 • up to Week 16
|
1.0%
1/98 • up to Week 16
|
0.00%
0/96 • up to Week 16
|
0.00%
0/99 • up to Week 16
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/97 • up to Week 16
|
0.00%
0/98 • up to Week 16
|
1.0%
1/96 • up to Week 16
|
0.00%
0/99 • up to Week 16
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.0%
1/97 • up to Week 16
|
0.00%
0/98 • up to Week 16
|
0.00%
0/96 • up to Week 16
|
0.00%
0/99 • up to Week 16
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/97 • up to Week 16
|
1.0%
1/98 • up to Week 16
|
0.00%
0/96 • up to Week 16
|
0.00%
0/99 • up to Week 16
|
|
Vascular disorders
Thrombophlebitis superficial
|
1.0%
1/97 • up to Week 16
|
0.00%
0/98 • up to Week 16
|
0.00%
0/96 • up to Week 16
|
0.00%
0/99 • up to Week 16
|
Other adverse events
| Measure |
Placebo
n=97 participants at risk
Participants received placebo matched to M2951 orally for 12 weeks.
|
M2951 25 mg QD
n=98 participants at risk
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
|
M2951 75 mg QD
n=96 participants at risk
Participants received 75 mg of M2951 orally QD for 12 weeks.
|
M2951 50 mg BID
n=99 participants at risk
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.2%
6/97 • up to Week 16
|
2.0%
2/98 • up to Week 16
|
3.1%
3/96 • up to Week 16
|
7.1%
7/99 • up to Week 16
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
0.00%
0/97 • up to Week 16
|
5.1%
5/98 • up to Week 16
|
0.00%
0/96 • up to Week 16
|
2.0%
2/99 • up to Week 16
|
|
Nervous system disorders
Headache
|
5.2%
5/97 • up to Week 16
|
6.1%
6/98 • up to Week 16
|
5.2%
5/96 • up to Week 16
|
8.1%
8/99 • up to Week 16
|
Additional Information
Communication Center
Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER