Trial Outcomes & Findings for A Study to Evaluate the Effectiveness of Infliximab and Changes in Hand and Wrist Magnetic Resonance Imaging (MRI) in Participants With Active Rheumatoid Arthritis (RA) (P08136) (NCT NCT01313520)

NCT ID: NCT01313520

Last Updated: 2017-05-10

Results Overview

Dynamic Contrast Enhanced (DCE) Magnetic Resonance Imaging (MRI) was performed on one hand at baseline, and then at treatment week 14 to measure the rate constant of transfer of contrast (Ktrans).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

61 participants

Primary outcome timeframe

Baseline and week 14

Results posted on

2017-05-10

Participant Flow

Participant milestones

Participant milestones
Measure
Infliximab
3 mg/kg of Infliximab intravenous infusion
Placebo
saline via intravenous infusion
Overall Study
STARTED
30
31
Overall Study
COMPLETED
30
31
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Effectiveness of Infliximab and Changes in Hand and Wrist Magnetic Resonance Imaging (MRI) in Participants With Active Rheumatoid Arthritis (RA) (P08136)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 Participants
saline via intravenous infusion
Total
n=61 Participants
Total of all reporting groups
Age, Continuous
50.3 years
STANDARD_DEVIATION 9.5 • n=5 Participants
50.1 years
STANDARD_DEVIATION 10.7 • n=7 Participants
50.2 years
STANDARD_DEVIATION 10.04 • n=5 Participants
Sex: Female, Male
Female
28 Participants
n=5 Participants
28 Participants
n=7 Participants
56 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 14

Population: Participants treated with infliximab or placebo

Dynamic Contrast Enhanced (DCE) Magnetic Resonance Imaging (MRI) was performed on one hand at baseline, and then at treatment week 14 to measure the rate constant of transfer of contrast (Ktrans).

Outcome measures

Outcome measures
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 Participants
saline via intravenous infusion
Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans)
-0.2 min ^-1
Interval -0.3 to -0.1
0.1 min ^-1
Interval 0.0 to 0.2

SECONDARY outcome

Timeframe: Baseline and week 14

Population: Participants treated with Infliximab or Placebo

ACR20 requires that both tender and swollen joint counts improve by at least 20% from baseline, as well as a 20% improvement in at least 3 other core measures from the following: pain, patient's and physician's global assessment, physical disability and C-reactive protein (CRP).

Outcome measures

Outcome measures
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 Participants
saline via intravenous infusion
Percentage of Responders With a 20% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR20).
56.7 percentage of responders
Interval 41.9 to 70.4
32.3 percentage of responders
Interval 20.3 to 47.0

SECONDARY outcome

Timeframe: Baseline and week 14

Population: Participants treated with Infliximab or placebo

ACR50 requires that both tender and swollen joint counts improve by at least 50% from baseline, as well as a 50% improvement in at least 3 other core measures from the following: pain, patient's and physician's global assessment, physical disability and CRP.

Outcome measures

Outcome measures
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 Participants
saline via intravenous infusion
Percentage of Responders With a 50% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR50).
20.0 percentage of responders
Interval 10.7 to 34.2
0 percentage of responders
Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: Participants treated with Infliximab or placebo

Clinical disease activity score (DAS28 CRP) is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), Patient Global Assessment of Disease Status (GADP) on a 100 mm visual analog scale (VAS) and concentration of CRP. Ktrans is the volume transfer rate from the blood plasma to the enhancing synovium. The individual endpoints are standardized using z-scores, then the z-scores are averaged to create a composite endpoint by use of O'Brien's global statistic.

Outcome measures

Outcome measures
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 Participants
saline via intravenous infusion
Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Ktrans.
-0.8 Z-score
95% Confidence Interval 0.3 • Interval -1.3 to -0.3
0.8 Z-score
95% Confidence Interval 0.2 • Interval 0.3 to 1.2

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: Participants treated with Infliximab or placebo

DAS28 CRP is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), GADP on a 100 mm VAS and concentration of CRP. RAMRIS Synovitis is an ordinal scoring system of hand synovitis that is scored from 0 to 3 in 8 locations, ranging from 0 to 24 total. RAMRIS Osteitis is an ordinal scoring system of hand osteitis that is scored from 0 to 3 in 25 locations, ranging from 0 to 75 total. The individual endpoints are standardized using z-scores, then the z-scores are averaged to create a composite endpoint by use of O'Brien's global statistic.

Outcome measures

Outcome measures
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 Participants
saline via intravenous infusion
Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Rheumatoid Arthritis MRI Score (RAMRIS) Synovitis + RAMRIS Osteitis.
-0.7 Z-score
95% Confidence Interval 0.3 • Interval -1.3 to -0.2
0.8 Z-score
95% Confidence Interval 0.2 • Interval 0.2 to 1.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 14

Population: Participants treated with infliximab or placebo

DAS28 CRP is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), GADP on a 100 mm VAS and concentration of serum CRP. Scores can range from 2-10; with higher values corresponding to higher disease activity, and lower values to better outcomes.

Outcome measures

Outcome measures
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 Participants
saline via intravenous infusion
Change From Baseline in DAS28 CRP.
-1.8 units on a scale
95% Confidence Interval 0.18 • Interval -2.2 to -1.5
-0.8 units on a scale
95% Confidence Interval 0.18 • Interval -1.2 to -0.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 14

Population: Participants treated with infliximab or placebo

RAMRIS Synovitis is an ordinal scoring system of hand synovitis that is scored from 0 to 3 in 8 locations. The scores can range from 0 to 24, with higher values corresponding to higher disease activity, and lower values to better outcomes.

Outcome measures

Outcome measures
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 Participants
saline via intravenous infusion
Change From Baseline in RAMRIS Synovitis.
-2.30 units on a scale
Standard Deviation 4.25 • Interval 0.64 to 1.55
0.24 units on a scale
Standard Deviation 1.98

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 14

Population: Participants treated with infliximab or placebo. One participant in the placebo group missing a baseline value was not included in the analysis.

RAMRIS Osteitis is an ordinal scoring system of hand osteitis that is scored from 0 to 3 in 25 locations. The scores can range from 0 to 75, with higher values corresponding to higher disease activity, and lower values to better outcomes.

Outcome measures

Outcome measures
Measure
Infliximab
n=30 Participants
3 mg/kg of Infliximab intravenous infusion
Placebo
n=30 Participants
saline via intravenous infusion
Change From Baseline in RAMRIS Osteitis.
-3.10 units on a scale
Standard Deviation 5.04 • Interval -2.0 to -1.5
0.48 units on a scale
Standard Deviation 3.22 • Interval -1.0 to -0.5

Adverse Events

Infliximab

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Infliximab
n=30 participants at risk
3 mg/kg of Infliximab intravenous infusion
Placebo
n=31 participants at risk
saline via intravenous infusion
Cardiac disorders
Palpitations
6.7%
2/30 • Number of events 2
0.00%
0/31
Gastrointestinal disorders
Abdominal Pain
0.00%
0/30
6.5%
2/31 • Number of events 2
Musculoskeletal and connective tissue disorders
Joint Swelling
13.3%
4/30 • Number of events 4
19.4%
6/31 • Number of events 6
Nervous system disorders
Headache
6.7%
2/30 • Number of events 2
0.00%
0/31

Additional Information

Vice President, Late Stage Development Group Leader

Merck Sharp & Dohme Corp.

Results disclosure agreements

  • Principal investigator is a sponsor employee The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor has the right to review and comment on publications, abstracts, slides and manuscripts and on the data analysis and presentation.
  • Publication restrictions are in place

Restriction type: OTHER