Trial Outcomes & Findings for Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis (NCT NCT00361634)

NCT ID: NCT00361634

Last Updated: 2013-09-17

Results Overview

Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 29. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 14 participants
• Primary outcome timeframe: Day 1 to Day 29
• Results posted on: 2013-09-17

Participant Flow

Participants were enrolled from 13 December 2006 through 27 April 2009

Participant milestones

Measure	Etanercept Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Overall Study STARTED	14
Overall Study Treated	13
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Etanercept Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	Etanercept n=14 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Age Continuous	50.6 Years STANDARD_DEVIATION 14.3 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	8 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 29

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available Day 29 data are included in the analysis.

Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 29. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

Outcome measures

Measure	Etanercept n=13 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-29	15.04 Percent change Standard Deviation 70.53

PRIMARY outcome

Timeframe: Day 1 to Day 57

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 57. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-57	40.75 Percent change Standard Deviation 77.28

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 85. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, increases in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-85	55.00 Percent change Standard Deviation 136.97

PRIMARY outcome

Timeframe: Day 1 to Day 29

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 29. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

Outcome measures

Measure	Etanercept n=13 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in Synovial Initial Area Under the (Contrast-time) Curve (IAUC) From Days 1-29	8.64 Percent change Standard Deviation 59.65

PRIMARY outcome

Timeframe: Day 1 to Day 57

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 57. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in the Synovial Initial Area Under the Contrast-Tme Curve (IAUC) From Days 1-57	15.30 Percent change Standard Deviation 33.98

PRIMARY outcome

Timeframe: Day 1 to Day 85

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 85. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in the Synovial Initial Area Under the Contrast-Time Curve (IAUC) From Days 1-85	34.54 Percent change Standard Deviation 84.91

SECONDARY outcome

Timeframe: Day 1 to Day 29

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 29. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.

Outcome measures

Measure	Etanercept n=13 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in Synovial Volume From Days 1-29	-4.15 Percent change Standard Deviation 46.54

SECONDARY outcome

Timeframe: Day 1 to Day 57

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 57. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.

Outcome measures

Measure	Etanercept n=11 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in Synovial Volume From Days 1-57	-6.52 Percent change Standard Deviation 31.47

SECONDARY outcome

Timeframe: Day 1 to Day 85

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 85. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Percent Change in Synovial Volume From Days 1-85	7.75 Percent change Standard Deviation 55.33

SECONDARY outcome

Timeframe: Day -28 to Day 29

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 29 and from study day -28 to study day 1.

Outcome measures

Measure	Etanercept n=13 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 29	-50.24 percent change Standard Deviation 231.80

SECONDARY outcome

Timeframe: Day -28 to Day 57

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 57 and from study day -28 to study day 1.

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 57	-49.96 percent change Standard Deviation 265.51

SECONDARY outcome

Timeframe: Day -28 to Day 85

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 85 and from study day -28 to study day 1

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 85	-35.72 percent change Standard Deviation 293.47

SECONDARY outcome

Timeframe: Day -28 to Day 29

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 29 and from Day -28 to Day 1

Outcome measures

Measure	Etanercept n=13 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 29	-5.96 percent change Standard Deviation 126.57

SECONDARY outcome

Timeframe: Day -28 to Day 57

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 57 and from Day -28 to Day 1

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 57	-8.68 percent change Standard Deviation 127.57

SECONDARY outcome

Timeframe: Day -28 to Day 85

Population: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available data are included in the analysis.

Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 85 and from Day -28 to Day 1

Outcome measures

Measure	Etanercept n=10 Participants Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 85	10.55 percent change Standard Deviation 146.25

Adverse Events

Etanercept

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Etanercept n=13 participants at risk Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Cardiac disorders Palpitations	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Eye disorders Myodesopsia	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diarrhoea	15.4% 2/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Fatigue	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Influenza like illness	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Injection site erythema	15.4% 2/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Injection site haematoma	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Injection site reaction	23.1% 3/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Injection site urticaria	15.4% 2/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Malaise	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pyrexia	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Lower respiratory tract infection	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Nasopharyngitis	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Tinea pedis	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Urinary tract infection	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Limb injury	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Anxiety	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Mood swings	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Reproductive system and breast disorders Breast tenderness	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Reproductive system and breast disorders Postmenopausal haemorrhage	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	15.4% 2/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Dry skin	23.1% 3/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Pain of skin	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Pruritus	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Rash	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Rash pruritic	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Hot flush	7.7% 1/13 • From first dose date to 30 days after last dose (up to 16 weeks). The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial resul
• Publication restrictions are in place

Restriction type: OTHER