Trial Outcomes & Findings for A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Trial to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 in Participants With Rheumatoid Arthritis (MK-8457-010) (NCT NCT01651936)
NCT ID: NCT01651936
Last Updated: 2021-07-30
Results Overview
The DAS28-CRP is a continuous parameter based upon a statistically-derived index combining tender joints (28 joints; 0=absent, 1=present; TEN28), swollen joints (28 joints; 0=absent, 1=present; SW28), CRP (an inflammatory marker, decrease indicates improvement), and Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) (0=doing very well to 100=doing very poor; GH). It is defined as follows: DAS28-CRP = 0.56 × SQRT(TEN28) + 0.28 × SQRT(SW28) + 0.36 × ln (CRP+1) + 0.014 × GH + 0.96. The DAS28-CRP is a scale ranging from 0 to 10 with higher values indicating greater RA disease activity. This outcome measure applied to Base Study participants only.
TERMINATED
PHASE2
56 participants
Baseline and Week 12
2021-07-30
Participant Flow
This trial was conducted at 53 clinical centers in the United States, Australia, Columbia, Denmark, France, Greece, Hungary, Italy, New Zealand, Poland, South Africa, Spain, and in the United Kingdom. A total of 120 participants were screened and 56 were enrolled.
Participant milestones
| Measure |
Base Study: MK-8457
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
Placebo BID + MTX for up to 24 weeks in the Base Study
|
Extension Study: MK-8457
MK-8457 100 mg BID + MTX for up to 76 weeks in the Extension Study. Participants who completed or had early escape from the Base Study were eligible to enroll in the Extension Study.
|
|---|---|---|---|
|
Base Study
STARTED
|
30
|
26
|
0
|
|
Base Study
COMPLETED
|
3
|
1
|
0
|
|
Base Study
NOT COMPLETED
|
27
|
25
|
0
|
|
Extension Study
STARTED
|
0
|
0
|
14
|
|
Extension Study
COMPLETED
|
0
|
0
|
0
|
|
Extension Study
NOT COMPLETED
|
0
|
0
|
14
|
Reasons for withdrawal
| Measure |
Base Study: MK-8457
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
Placebo BID + MTX for up to 24 weeks in the Base Study
|
Extension Study: MK-8457
MK-8457 100 mg BID + MTX for up to 76 weeks in the Extension Study. Participants who completed or had early escape from the Base Study were eligible to enroll in the Extension Study.
|
|---|---|---|---|
|
Base Study
Adverse Event
|
3
|
0
|
0
|
|
Base Study
Withdrawal by Subject
|
1
|
1
|
0
|
|
Base Study
Early Escape
|
2
|
8
|
0
|
|
Base Study
Study terminated by sponsor
|
21
|
16
|
0
|
|
Extension Study
Lack of Efficacy
|
0
|
0
|
1
|
|
Extension Study
Study terminated by sponsor
|
0
|
0
|
13
|
Baseline Characteristics
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Trial to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 in Participants With Rheumatoid Arthritis (MK-8457-010)
Baseline characteristics by cohort
| Measure |
Base Study: MK-8457
n=30 Participants
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
n=26 Participants
Placebo BID + MTX for up to 24 weeks in the Base Study
|
Total
n=56 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.8 Years
STANDARD_DEVIATION 12.7 • n=5 Participants
|
59.3 Years
STANDARD_DEVIATION 10.8 • n=7 Participants
|
58.5 Years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Age, Customized
<65 years
|
21 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Age, Customized
≥65 years
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: Randomized participants in the Base Study who received at least one dose of study drug and had both Baseline and Week 12 DAS28-CRP measurements
The DAS28-CRP is a continuous parameter based upon a statistically-derived index combining tender joints (28 joints; 0=absent, 1=present; TEN28), swollen joints (28 joints; 0=absent, 1=present; SW28), CRP (an inflammatory marker, decrease indicates improvement), and Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) (0=doing very well to 100=doing very poor; GH). It is defined as follows: DAS28-CRP = 0.56 × SQRT(TEN28) + 0.28 × SQRT(SW28) + 0.36 × ln (CRP+1) + 0.014 × GH + 0.96. The DAS28-CRP is a scale ranging from 0 to 10 with higher values indicating greater RA disease activity. This outcome measure applied to Base Study participants only.
Outcome measures
| Measure |
Base Study: MK-8457
n=13 Participants
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
n=18 Participants
Placebo BID + MTX for up to 24 weeks in the Base Study
|
|---|---|---|
|
Change From Baseline in Disease Activity Score (DAS28) as Measured by C-Reactive Protein (CRP) at Week 12
|
-1.83 Units on a scale
Interval -2.58 to -1.09
|
-1.31 Units on a scale
Interval -2.01 to -0.62
|
SECONDARY outcome
Timeframe: Week 12Population: Randomized participants in the Base Study who received at least one dose of study drug and had at least one post-baseline ACR20 measurement (last observation carried forward)
ACR responses are numerical measurements of improvement in multiple disease assessment criteria. An ACR20 response is defined as a ≥20% improvement in 1) swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2) ≥20% improvement in 3 of the following 5 assessments: a) a participant's overall assessment of pain on a visual analog scale (VAS, no pain =0 to extreme pain =100); b) Patient's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100); c) Investigator's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100 ; d) participant's assessment of function across 8 functional areas as measured by Health Assessment Questionnaire (HAQ), total scores ranging from no difficulty =0 to inability to perform tasks =24; and e) serum C-Reactive Protein (decrease indicates improvement). This outcome measure applied to Base Study participants only.
Outcome measures
| Measure |
Base Study: MK-8457
n=30 Participants
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
n=26 Participants
Placebo BID + MTX for up to 24 weeks in the Base Study
|
|---|---|---|
|
Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
|
26.67 Percentage of participants
|
26.92 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: Due to the early termination of the study, analysis for this outcome measure was not performed according to the protocol because complete data were not available.
ACR responses are numerical measurements of improvement in multiple disease assessment criteria. An ACR20 response is defined as a ≥20% improvement in 1) swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2) ≥20% improvement in 3 of the following 5 assessments: a) a participant's overall assessment of pain on a visual analog scale (VAS, no pain =0 to extreme pain =100); b) Patient's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100); c) Investigator's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100 ; d) participant's assessment of function across 8 functional areas as measured by Health Assessment Questionnaire (HAQ), total scores ranging from no difficulty =0 to inability to perform tasks =24; and e) serum C-Reactive Protein (decrease indicates improvement). This outcome measure applied to Base Study participants only.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 12Population: Randomized participants in the Base Study who received at least one dose of study drug and had at least one post-baseline ACR50 measurement (last observation carried forward)
ACR responses are numerical measurements of improvement in multiple disease assessment criteria. An ACR50 response is defined as a ≥50% improvement in 1) swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2) ≥50% improvement in 3 of the following 5 assessments: a) a participant's overall assessment of pain on a visual analog scale (VAS, no pain =0 to extreme pain =100); b) Patient's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100); c) Investigator's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100 ; d) participant's assessment of function across 8 functional areas as measured by Health Assessment Questionnaire (HAQ), total scores ranging from no difficulty =0 to inability to perform tasks =24; and e) serum C-Reactive Protein (decrease indicates improvement). This outcome measure applied to Base Study participants only.
Outcome measures
| Measure |
Base Study: MK-8457
n=30 Participants
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
n=26 Participants
Placebo BID + MTX for up to 24 weeks in the Base Study
|
|---|---|---|
|
Percentage of Participants Achieving an ACR50 Response at Week 12
|
20.00 Percentage of participants
|
11.54 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Due to the early termination of the study, analysis for this outcome measure was not performed according to the protocol because complete data were not available.
The DAS28-CRP is a continuous parameter based upon a statistically-derived index combining tender joints (28 joints; 0=absent, 1=present; TEN28), swollen joints (28 joints; 0=absent, 1=present; SW28), CRP (decrease indicates improvement), and Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) (0=doing very well to 100=doing very poor; GH, ). It is defined as follows: DAS28-CRP = 0.56 × SQRT(TEN28) + 0.28 × SQRT(SW28) + 0.36 × ln (CRP+1) + 0.014 × GH + 0.96. The DAS28-CRP is a scale ranging from 0 to 10 with higher values indicating greater RA disease activity. This outcome measure applied to Base Study participants only.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Randomized participants in the Base Study who received at least one dose of study drug and had both Baseline and Week 12 HAQ Disability Index measurement
The functional status of the participant was assessed using the Disability Index of the HAQ on a Likert scale. This 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. The overall score for the Disability Index is the mean of the 8 functional area scores and also ranges from 0 to 3, with a lower score indicating less disability. A negative change from Baseline indicates improvement. This outcome measure applied to Base Study participants only.
Outcome measures
| Measure |
Base Study: MK-8457
n=13 Participants
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
n=18 Participants
Placebo BID + MTX for up to 24 weeks in the Base Study
|
|---|---|---|
|
Change From Baseline in the Health Assessment Questionnaire Disability (HAQ Disability Index) at Week 12
|
-0.67 Units on a scale
Interval -0.95 to -0.39
|
-0.26 Units on a scale
Interval -0.52 to -0.01
|
SECONDARY outcome
Timeframe: Week 24Population: Due to the early termination of the study, analysis for this outcome measure was not performed according to the protocol because complete data were not available.
ACR responses are numerical measurements of improvement in multiple disease assessment criteria. An ACR50 response is defined as a ≥50% improvement in 1) swollen joint count (66 joints) and tender joint count (68 joints) (0=Absent; 1=Present) and 2) ≥50% improvement in 3 of the following 5 assessments: a) a participant's overall assessment of pain on a visual analog scale (VAS, 0=no pain to 100=extreme pain); b) Patient's Global Assessment of Disease Activity VAS (0=doing very well to 100=doing very poor); c) Investigator's Global Assessment of Disease Activity VAS (0=doing very well to 100=doing very poor; d) participant's assessment of function across 8 functional areas as measured by Health Assessment Questionnaire (HAQ), total scores ranging from 0=no difficulty to 24=inability to perform tasks; and e) CRP (decrease indicates improvement). This outcome measure applied to Base Study participants only.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Due to the early termination of the study, analysis for this outcome measure was not performed according to the protocol because complete data were not available.
The functional status of the participant was assessed using the Disability Index of the HAQ on a Likert scale. This 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. The overall score for the Disability Index is the mean of the 8 functional area scores and also ranges from 0 to 3, with a lower score indicating less disability. A negative change from Baseline indicates improvement. This outcome measure applied to Base Study participants only.
Outcome measures
Outcome data not reported
Adverse Events
Base Study: MK-8457
Base Study: Placebo
Extension Study: MK-8457
Serious adverse events
| Measure |
Base Study: MK-8457
n=30 participants at risk
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
n=26 participants at risk
Placebo BID + MTX for up to 24 weeks in the Base Study
|
Extension Study: MK-8457
n=14 participants at risk
MK-8457 100 mg BID + MTX for up to 76 weeks in the Extension Study. Participants who completed or had early escape from the Base Study were eligible to enroll in the Extension Study
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
3.3%
1/30 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Gastrointestinal disorders
Enterocolitis
|
3.3%
1/30 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Infections and infestations
Bronchitis
|
3.3%
1/30 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Infections and infestations
Lung infection
|
0.00%
0/30 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Injury, poisoning and procedural complications
Hip fracture
|
3.3%
1/30 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/30 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Investigations
White blood cell count decreased
|
3.3%
1/30 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
Other adverse events
| Measure |
Base Study: MK-8457
n=30 participants at risk
MK-8457 100 mg BID + MTX for up to 24 weeks in the Base Study
|
Base Study: Placebo
n=26 participants at risk
Placebo BID + MTX for up to 24 weeks in the Base Study
|
Extension Study: MK-8457
n=14 participants at risk
MK-8457 100 mg BID + MTX for up to 76 weeks in the Extension Study. Participants who completed or had early escape from the Base Study were eligible to enroll in the Extension Study
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
6.7%
2/30 • Number of events 2 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/30 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
2/30 • Number of events 2 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
2/30 • Number of events 2 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
5/30 • Number of events 5 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
3.8%
1/26 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
14.3%
2/14 • Number of events 3 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/30 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/30 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/30 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Injury, poisoning and procedural complications
Mouth injury
|
0.00%
0/30 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Investigations
Blood pressure increased
|
3.3%
1/30 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
3.8%
1/26 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
6.7%
2/30 • Number of events 2 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/14 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/30 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
0.00%
0/26 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
7.1%
1/14 • Number of events 1 • Base Study: up to 24 weeks: Extension Study: up to approximately 40 weeks
|
Additional Information
Senior Vice President, Global Clinical Development
Merck, Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
- Publication restrictions are in place
Restriction type: OTHER