Trial Outcomes & Findings for Efficacy and Safety Study of MP-435 in Combination With Methotrexate (MTX) in Patients With Rheumatoid Arthritis (NCT NCT01143337)
NCT ID: NCT01143337
Last Updated: 2026-01-06
Results Overview
ACR 20 response is a decrease of at least 20 per cent in both tender and swollen joint count \[TJC and SJC\] and in 3 to 5 assessments (participant's assessment of pain visual analog scale \[VAS\] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity \[0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively\]; Health Assessment Questionnaire \[HAQ-DI\]: 20-questions on life activities \[0, no difficulty to 3, inability to perform a task\]; C-reactive protein\[CRP\]).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
112 participants
Primary outcome timeframe
Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time)
Results posted on
2026-01-06
Participant Flow
Participant milestones
| Measure |
Placebo
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
|
MP-435 400mg BID
MP-435 400mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
|
|---|---|---|---|
|
Overall Study
STARTED
|
49
|
50
|
13
|
|
Overall Study
COMPLETED
|
39
|
39
|
1
|
|
Overall Study
NOT COMPLETED
|
10
|
11
|
12
|
Reasons for withdrawal
| Measure |
Placebo
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
|
MP-435 400mg BID
MP-435 400mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
9
|
5
|
|
Overall Study
Lack of Efficacy
|
6
|
2
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
|
Overall Study
Other reason
|
0
|
0
|
5
|
Baseline Characteristics
Efficacy and Safety Study of MP-435 in Combination With Methotrexate (MTX) in Patients With Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Placebo
n=46 Participants
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
n=47 Participants
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
MP-435 400mg:
There were 13 patients who randomized 400 mg bid group when they were discontinued dosing. At this point, it was found that there were Four patients who increased ALT more than three times of upper limit of normal in this dosing group. Therefore, patients who randomized to this dosing group were discontinued and also new inclusion was stopped in this point.
Primary analysis of this study result was Par Protocol Set ( PPS ). Because examination for 400 mg bid group was discontinued, this arm data was excluded from PPS analysis.
|
Total
n=93 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
< 40 years
|
5 participants
n=37 Participants
|
8 participants
n=56 Participants
|
13 participants
n=82 Participants
|
|
Age, Customized
40 - 50 years
|
9 participants
n=37 Participants
|
7 participants
n=56 Participants
|
16 participants
n=82 Participants
|
|
Age, Customized
50 - 60 years
|
13 participants
n=37 Participants
|
13 participants
n=56 Participants
|
26 participants
n=82 Participants
|
|
Age, Customized
60 - 70 years
|
15 participants
n=37 Participants
|
12 participants
n=56 Participants
|
27 participants
n=82 Participants
|
|
Age, Customized
≧ 70 years
|
4 participants
n=37 Participants
|
7 participants
n=56 Participants
|
11 participants
n=82 Participants
|
|
Sex: Female, Male
Female
|
43 Participants
n=37 Participants
|
43 Participants
n=56 Participants
|
86 Participants
n=82 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=37 Participants
|
4 Participants
n=56 Participants
|
7 Participants
n=82 Participants
|
PRIMARY outcome
Timeframe: Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time)ACR 20 response is a decrease of at least 20 per cent in both tender and swollen joint count \[TJC and SJC\] and in 3 to 5 assessments (participant's assessment of pain visual analog scale \[VAS\] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity \[0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively\]; Health Assessment Questionnaire \[HAQ-DI\]: 20-questions on life activities \[0, no difficulty to 3, inability to perform a task\]; C-reactive protein\[CRP\]).
Outcome measures
| Measure |
Placebo
n=46 Participants
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
n=47 Participants
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
MP-435 400mg:
There were 13 patients who randomized 400 mg bid group when they were discontinued dosing. At this point, it was found that there were Four patients who increased ALT more than three times of upper limit of normal in this dosing group. Therefore, patients who randomized to this dosing group were discontinued and also new inclusion was stopped in this point.
Primary analysis of this study result was Par Protocol Set ( PPS ). Because examination for 400 mg bid group was discontinued, this arm data was excluded from PPS analysis.
|
|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 20 (ACR 20) Response
Week 2
|
10.9 percentage of participants
Interval 3.6 to 23.6
|
19.1 percentage of participants
Interval 9.1 to 33.3
|
|
Percentage of Participants Achieving American College of Rheumatology 20 (ACR 20) Response
Week 4
|
24.4 percentage of participants
Interval 12.9 to 39.5
|
39.1 percentage of participants
Interval 25.1 to 54.6
|
|
Percentage of Participants Achieving American College of Rheumatology 20 (ACR 20) Response
Week 6
|
23.3 percentage of participants
Interval 11.8 to 38.6
|
39.0 percentage of participants
Interval 24.2 to 55.5
|
|
Percentage of Participants Achieving American College of Rheumatology 20 (ACR 20) Response
Week 8
|
34.9 percentage of participants
Interval 21.0 to 50.9
|
45.0 percentage of participants
Interval 29.3 to 61.5
|
|
Percentage of Participants Achieving American College of Rheumatology 20 (ACR 20) Response
Week 12
|
39.5 percentage of participants
Interval 24.0 to 56.6
|
39.5 percentage of participants
Interval 24.0 to 56.6
|
|
Percentage of Participants Achieving American College of Rheumatology 20 (ACR 20) Response
LOCF (Week 12 or discontinuation time)
|
34.8 percentage of participants
Interval 21.4 to 50.2
|
42.6 percentage of participants
Interval 28.3 to 57.8
|
SECONDARY outcome
Timeframe: Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time)ACR 50 response is a decrease of at least 50 per cent in both tender and swollen joint count and in 3 to 5 assessments (participant's assessment of pain VAS with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity \[0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively\]; HAQ-DI: 20-questions on life activities \[0, no difficulty to 3, inability to perform a task\]; CRP).
Outcome measures
| Measure |
Placebo
n=46 Participants
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
n=47 Participants
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
MP-435 400mg:
There were 13 patients who randomized 400 mg bid group when they were discontinued dosing. At this point, it was found that there were Four patients who increased ALT more than three times of upper limit of normal in this dosing group. Therefore, patients who randomized to this dosing group were discontinued and also new inclusion was stopped in this point.
Primary analysis of this study result was Par Protocol Set ( PPS ). Because examination for 400 mg bid group was discontinued, this arm data was excluded from PPS analysis.
|
|---|---|---|
|
Percentage of Participants Achieving ACR 50 Response
Week 2
|
4.3 percentage of participants
Interval 0.5 to 14.8
|
2.1 percentage of participants
Interval 0.1 to 11.3
|
|
Percentage of Participants Achieving ACR 50 Response
Week 4
|
8.9 percentage of participants
Interval 2.5 to 21.2
|
4.3 percentage of participants
Interval 0.5 to 14.8
|
|
Percentage of Participants Achieving ACR 50 Response
Week 6
|
7.0 percentage of participants
Interval 1.5 to 19.1
|
12.2 percentage of participants
Interval 4.1 to 26.2
|
|
Percentage of Participants Achieving ACR 50 Response
Week 8
|
9.3 percentage of participants
Interval 2.6 to 22.1
|
17.5 percentage of participants
Interval 7.3 to 32.8
|
|
Percentage of Participants Achieving ACR 50 Response
Week 12
|
13.2 percentage of participants
Interval 4.4 to 28.1
|
15.8 percentage of participants
Interval 6.0 to 31.1
|
|
Percentage of Participants Achieving ACR 50 Response
LOCF (Week 12 or discontinuation time)
|
13.0 percentage of participants
Interval 4.9 to 26.3
|
14.9 percentage of participants
Interval 6.2 to 28.3
|
SECONDARY outcome
Timeframe: Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time)ACR 70 response is a decrease of at least 70 per cent in both tender and swollen joint count and in 3 to 5 assessments (participant's assessment of pain VAS with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity \[0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively\]; HAQ-DI: 20-questions on life activities \[0, no difficulty to 3, inability to perform a task\]; CRP).
Outcome measures
| Measure |
Placebo
n=46 Participants
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
n=47 Participants
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
MP-435 400mg:
There were 13 patients who randomized 400 mg bid group when they were discontinued dosing. At this point, it was found that there were Four patients who increased ALT more than three times of upper limit of normal in this dosing group. Therefore, patients who randomized to this dosing group were discontinued and also new inclusion was stopped in this point.
Primary analysis of this study result was Par Protocol Set ( PPS ). Because examination for 400 mg bid group was discontinued, this arm data was excluded from PPS analysis.
|
|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 70 (ACR 70) Response
Week 8
|
2.3 percentage of participants
Interval 0.1 to 12.3
|
0.0 percentage of participants
Interval 0.0 to 8.8
|
|
Percentage of Participants Achieving American College of Rheumatology 70 (ACR 70) Response
Week 2
|
0.0 percentage of participants
Interval 0.0 to 7.7
|
0.0 percentage of participants
Interval 0.0 to 7.5
|
|
Percentage of Participants Achieving American College of Rheumatology 70 (ACR 70) Response
Week 4
|
2.2 percentage of participants
Interval 0.1 to 11.8
|
0.0 percentage of participants
Interval 0.0 to 7.7
|
|
Percentage of Participants Achieving American College of Rheumatology 70 (ACR 70) Response
Week 6
|
2.3 percentage of participants
Interval 0.1 to 12.3
|
0.0 percentage of participants
Interval 0.0 to 8.6
|
|
Percentage of Participants Achieving American College of Rheumatology 70 (ACR 70) Response
Week 12
|
2.6 percentage of participants
Interval 0.1 to 13.8
|
2.6 percentage of participants
Interval 0.1 to 13.8
|
|
Percentage of Participants Achieving American College of Rheumatology 70 (ACR 70) Response
LOCF (Week 12 or discontinuation time)
|
2.2 percentage of participants
Interval 0.1 to 11.5
|
4.3 percentage of participants
Interval 0.5 to 14.5
|
SECONDARY outcome
Timeframe: LOCF (Week 12 or discontinuation time)DAS28 (CRP) is calculated using TJC, SJC C-Reactive Protein ( CRP in mg/dL ), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.36 x log (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. DAS28 (ESR) is calculated using TJC, SJC erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x log (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative change score indicates improvement. Higher score indicated more disease activity. DAS28 =\<3.2 implied low disease activity, \>3.2 to 5.1 implied moderate disease activity, \>5.1 implied high disease activity.
Outcome measures
| Measure |
Placebo
n=46 Participants
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
n=47 Participants
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
MP-435 400mg:
There were 13 patients who randomized 400 mg bid group when they were discontinued dosing. At this point, it was found that there were Four patients who increased ALT more than three times of upper limit of normal in this dosing group. Therefore, patients who randomized to this dosing group were discontinued and also new inclusion was stopped in this point.
Primary analysis of this study result was Par Protocol Set ( PPS ). Because examination for 400 mg bid group was discontinued, this arm data was excluded from PPS analysis.
|
|---|---|---|
|
Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
DAS 28 (CRP) Week 0
|
4.18 units on a scale
Standard Deviation 0.80
|
4.41 units on a scale
Standard Deviation 0.77
|
|
Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
DAS 28 (CRP) Week 12 or discontinuation time
|
3.48 units on a scale
Standard Deviation 1.26
|
3.54 units on a scale
Standard Deviation 1.15
|
|
Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
DAS 28 (ESR) Week 0
|
5.59 units on a scale
Standard Deviation 0.82
|
5.8 units on a scale
Standard Deviation 0.76
|
|
Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
DAS 28 (ESR) Week 12 or discontinuation time
|
4.87 units on a scale
Standard Deviation 1.30
|
4.94 units on a scale
Standard Deviation 1.15
|
SECONDARY outcome
Timeframe: LOCF (Week 12 or discontinuation time)ACR components are tender joints count (TJC), swollen joints count (SJC), participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ-DI\]); and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR).
Outcome measures
| Measure |
Placebo
n=46 Participants
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
n=47 Participants
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
MP-435 400mg:
There were 13 patients who randomized 400 mg bid group when they were discontinued dosing. At this point, it was found that there were Four patients who increased ALT more than three times of upper limit of normal in this dosing group. Therefore, patients who randomized to this dosing group were discontinued and also new inclusion was stopped in this point.
Primary analysis of this study result was Par Protocol Set ( PPS ). Because examination for 400 mg bid group was discontinued, this arm data was excluded from PPS analysis.
|
|---|---|---|
|
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
TJC
|
33.72 percentage of change from baseline
Standard Deviation 52.21
|
36.94 percentage of change from baseline
Standard Deviation 50.57
|
|
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
SJC
|
35.74 percentage of change from baseline
Standard Deviation 91.22
|
44.44 percentage of change from baseline
Standard Deviation 33.00
|
|
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
participant assessment
|
-2.14 percentage of change from baseline
Standard Deviation 76.99
|
-6.67 percentage of change from baseline
Standard Deviation 187.29
|
|
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
participant global assessment of disease activity
|
-11.57 percentage of change from baseline
Standard Deviation 98.92
|
4.53 percentage of change from baseline
Standard Deviation 128.92
|
|
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
physician global assessment of disease activity
|
21.6 percentage of change from baseline
Standard Deviation 43.85
|
33.06 percentage of change from baseline
Standard Deviation 35.39
|
|
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
HAQ-DI
|
5.84 percentage of change from baseline
Standard Deviation 61.48
|
14.78 percentage of change from baseline
Standard Deviation 49.80
|
|
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
CRP
|
-34.13 percentage of change from baseline
Standard Deviation 147.17
|
-46.01 percentage of change from baseline
Standard Deviation 150.97
|
|
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components
ESR
|
1.00 percentage of change from baseline
Standard Deviation 27.76
|
-12.01 percentage of change from baseline
Standard Deviation 46.95
|
Adverse Events
Placebo
Serious events: 3 serious events
Other events: 11 other events
Deaths: 0 deaths
MP-435 100mg BID
Serious events: 0 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=49 participants at risk
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
n=50 participants at risk
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
MP-435 400mg:
There were 13 patients who randomized 400 mg bid group when they were discontinued dosing. At this point, it was found that there were Four patients who increased ALT more than three times of upper limit of normal in this dosing group. Therefore, patients who randomized to this dosing group were discontinued and also new inclusion was stopped in this point.
Primary analysis of this study result was Par Protocol Set ( PPS ). Because examination for 400 mg bid group was discontinued, this arm data was excluded from PPS analysis.
|
|---|---|---|
|
Infections and infestations
Tuberculous pleurisy
|
2.0%
1/49
|
0.00%
0/50
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
2.0%
1/49
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
2.0%
1/49
|
0.00%
0/50
|
|
Investigations
Liver function test abnormal
|
2.0%
1/49
|
0.00%
0/50
|
Other adverse events
| Measure |
Placebo
n=49 participants at risk
MP-435 placebo-matching tablets, orally, twice daily. And stable dose (6-8 mg/week) Methotrexate(MTX) were administered as background therapy.
|
MP-435 100mg BID
n=50 participants at risk
MP-435 100mg, orally, twice daily. And stable dose (6-8 mg/week) MTX were administered as background therapy.
MP-435 400mg:
There were 13 patients who randomized 400 mg bid group when they were discontinued dosing. At this point, it was found that there were Four patients who increased ALT more than three times of upper limit of normal in this dosing group. Therefore, patients who randomized to this dosing group were discontinued and also new inclusion was stopped in this point.
Primary analysis of this study result was Par Protocol Set ( PPS ). Because examination for 400 mg bid group was discontinued, this arm data was excluded from PPS analysis.
|
|---|---|---|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/49
|
12.0%
6/50
|
|
Investigations
Liver function test abnormal
|
4.1%
2/49
|
16.0%
8/50
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
7/49
|
12.0%
6/50
|
|
Nervous system disorders
Headache
|
6.1%
3/49
|
4.0%
2/50
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER