- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01783015
Study of Etanercept in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to Adalimumab or Infliximab Plus Methotrexate (SERUM)
December 1, 2015 updated by: Pfizer
A Randomized, Double-blind, Placebo-controlled Study Of The Safety And Efficacy Of Etanercept In Subjects With Rheumatoid Arthritis Who Have Had An Inadequate Response To Adalimumab Or Infliximab Plus Methotrexate
The first 12 weeks of this study will compare the efficacy of etanercept 50 mg once-weekly to placebo in subjects with rheumatoid arthritis who have not responded well to infliximab or adalimumab plus methotrexate.
This comparison will be performed for all subjects and separately for subjects who are anti-drug antibody positive for one of these medications.
From week 12 to week 24, all subjects will receive etanercept 50 mg once-weekly.
The effect of anti-drug antibody status on the efficacy of etanercept as well as the safety profile of etanercept in these subjects will also be evaluated throughout the study.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
This study was prematurely terminated on June 25, 2014 due to significant and continuing delays in achieving the study B1801355 enrolment target.
The decision to stop the study was not driven by any safety concerns.
Study Type
Interventional
Enrollment (Actual)
16
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Western Australia
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Victoria Park, Western Australia, Australia, 6100
- RK Will Pty Ltd
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Bruxelles, Belgium, 1200
- Cliniques Universitaires Saint-Luc / Service de Rhumatologie
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Montpellier, France, 34295 cedex 5
- Hopital Lapeyronie
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Tseung Kwan O, NT, Hong Kong
- Tseung Kwan O Hospital
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New Territories
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Tseung Kwan O, New Territories, Hong Kong
- Tseung Kwan O Hospital
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Haifa, Israel, 31048
- Bnai Zion Medical Ctr Pharmacy
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Kfar Saba, Israel, 44281
- Meir Medical Center pharmacy
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Izhevsk, Russian Federation, 426063
- LLC "Alliance Biomedical - Russian Group"
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Kazan, Russian Federation, 420103
- LLC Research Medical Complex "Your Health" based on City Clinical Hospital #7
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Moscow, Russian Federation, 115522
- Scientific Institute of Rheumatology of Russian Academy of Medical Science
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Moscow, Russian Federation, 129301
- GBOU VPO Moscow State University of Medicine and Dentistry
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Barcelona, Spain, 08025
- Hospital de la Santa Creu i San Pau
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Málaga, Spain, 29009
- Hospital Regional Universitario Carlos Haya. Hospital Civil
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Málaga, Spain, 29010
- Hospital Regional Universitario Carlos Haya.
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Sevilla, Spain, 41010
- Hospital Infanta Luisa
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 79 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Met the 1987 ACR Revised Criteria for RA
- A history of inadequate response to infliximab or adalimumab in combination with methotrexate.
- A stable dose of oral methotrexate for at least 6 weeks before the baseline visit.
Exclusion Criteria:
- ACR functional class IV
- Prior treatment with etanercept; both infliximab and adalimumab; or any immunosuppressive biologic agent other than infliximab or adalimumab.
- Discontinuation of infliximab or adalimumab for a primary reason other than inadequate efficacy response.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Group A
Subjects who are mAb ADA positive
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Etanercept 50 mg once-weekly
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Experimental: Group B
Subjects who are mAb ADA negative
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Etanercept 50 mg once-weekly
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Placebo Comparator: Group C
Subjects who are mAb ADA positive
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Etanercept placebo once-weekly
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Placebo Comparator: Group D
Subjects who are mAb ADA negative
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Etanercept placebo once-weekly
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in the Disease Activity Score Based on a 28 Joint Count (DAS28-C-reactive Protein [CRP]) at Week 12.
Time Frame: Baseline, 12 weeks
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DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the c-reactive protein (CRP) and Subject General Health Visual Analogue Scale (VAS) assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).
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Baseline, 12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in the DAS28 at Week 24
Time Frame: Baseline, 24 weeks
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DAS28 calculated from the number of SJC and PJC using the 28 joints count, the CRP and and Subject General Health VAS assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).
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Baseline, 24 weeks
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Number of Participants With DAS28 <3.2
Time Frame: 12 weeks, 24 weeks
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Number of participants with DAS28 <3.2.
A score of < 3.2 implied low disease activity.
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12 weeks, 24 weeks
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Number of Participants With DAS28 <2.6
Time Frame: 12 weeks, 24 weeks
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Number of Participants with DAS28 <2.6.
A DAS28 < 2.6 implies remission.
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12 weeks, 24 weeks
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Number of Participants Achieving American College of Rheumatology 20% (ACR20) Response
Time Frame: 12 weeks, 24 weeks
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ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant's assessment of pain; Subject Global Assessment (SGA) of disease activity; Physician Global Assessment (PGA) of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP.
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12 weeks, 24 weeks
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Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Time Frame: 12 weeks, 24 weeks
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ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and ≥ 50% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.
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12 weeks, 24 weeks
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Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Time Frame: 12 weeks, 24 weeks
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ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and ≥ 70% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.
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12 weeks, 24 weeks
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Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response
Time Frame: 12 weeks, 24 weeks
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ACR90 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and ≥ 90% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.
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12 weeks, 24 weeks
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Number of Participants Achieving European League Against Rheumatism (EULAR) Good and/or Moderate Response.
Time Frame: 12 weeks, 24 weeks
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The Disease Activity Score Based on 28-joints Count based (DAS28-based) EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached.
Good responders: change from baseline >1.2 with DAS28 =< 3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to =<5.1 or change from baseline >0.6 to =<1.2 with DAS28 =<5.1; non-responders: change from baseline =< 0.6 or change from baseline >0.6 and =<1.2 with DAS28 >5.1.
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12 weeks, 24 weeks
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Number of Participants Achieving Low Disease Activity or Remission Based on Clinical Disease Activity Index (CDAI)
Time Frame: 12 weeks, 24 weeks
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The CDAI is the numerical sum of 4 outcome parameters: tender joint count (TJC) and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity.
CDAI total score = 0-76.
CDAI <= 2.8 indicates disease remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity.
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12 weeks, 24 weeks
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Number of Participants Achieving Low Disease Activity or Remission Based on Simplified Disease Activity Index (SDAI).
Time Frame: 12 weeks, 24 weeks
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The SDAI is the numerical sum of five outcome parameters: TJC) and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity, and CRP (mg/dL).
SDAI total score= 0-86.
SDAI <=3.3 indicates disease remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high disease activity.
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12 weeks, 24 weeks
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Change From Baseline in CDAI
Time Frame: Baseline, 12 weeks, 24 weeks
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Change from Baseline in CDAI scores was to be calculated.
The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity.
CDAI total score = 0-76.
CDAI <= 2.8 indicates disease remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high disease activity.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in SDAI.
Time Frame: Baseline, 12 weeks, 24 weeks
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Change from Baseline in SDAI scores were to be calculated.
The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity, and CRP (mg/dL).
SDAI total score= 0-86.
SDAI <=3.3 indicates disease remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high disease activity.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Number of Tender/Painful Joints
Time Frame: Baseline, 12 weeks, 24 weeks
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Change from Baseline in the number of tender/painful joints using the 28 joint count including shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees was to be calculated.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Number of Swollen Joints
Time Frame: Baseline, 12 weeks, 24 weeks
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Change from Baseline in the number of swollen joints including shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees was to be calculated.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Physician Global Assessment of Disease Activity
Time Frame: Baseline, 12 weeks, 24 weeks
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Change from Baseline in the PGA scores was to be estimated.
The Study Physician estimated the participant's overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity).
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Subject Global Assessment of Disease Activity
Time Frame: Baseline, 12 weeks, 24 weeks
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Change from Baseline in Subject Global Assessment of Disease Activity was to be estimated.
Participants were to assess their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity).
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Subject General Health VAS.
Time Frame: Baseline, 12 weeks, 24 weeks
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Subject General Health VAS assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Subject Pain
Time Frame: Baseline, 12 weeks, 24 weeks
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Subject Pain was to be measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no pain and 100 mm = most severe pain.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in CRP
Time Frame: Baseline, 12 weeks, 24 weeks
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The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay.
A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Health Assessment Questionnaire Disability and Discomfort Scales (HAQ-DI)
Time Frame: Baseline, 12 weeks, 24 weeks
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Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week.
Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do.
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.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Euro Quality of Life (Qol) EQ-5 Dimensions Questionnaire (EQ-5D)
Time Frame: Baseline, 12 weeks, 24 weeks
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The EuroQol-5 Dimensions (EQ-5D) is a participant-completed questionnaire designed to assess health related quality of life.
There are 2 components to the EQ-5D: a Health State Profile and a VAS.
For the Health State Profile, participants recorded their level of current health for 5 domains comprising a health profile: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Scores from the 5 domains may be used to calculate a single index value, also known as a utility score.
On the VAS participants were asked to rate their current health on a scale from 0 to 100 mm, where 0 represented the "worst imaginable health state" and 100 represented the "best imaginable health state."
In addition to a summary of mean changes, 1 categorical endpoint each based on EQ-5D utility score and 1 based on the VAS were derived and analyzed: EQ-5D utility score improvement ≥0.05 and EQ-5D VAS score >82.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Short Form-36 Health Survey (SF-36)
Time Frame: Baseline, 12 weeks, 24 weeks
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The 36-Item Short Form Health Survey (SF-36) is widely used 36-item questionnaire that measures general health-related quality of life in the following 8 domains: physical function, role limitations due to physical health, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health.
Scores for the 8 domains range from 0 to 100 where higher scores are better.
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Patient Acceptable Symptom State (PASS)
Time Frame: Baseline, 12 weeks, 24 weeks
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The Patient Acceptable Symptom State (PASS) was a participant-completed form in which participants were asked to "Think about all the ways your rheumatoid arthritis (RA) has affected you during the last 48 hours.
If you were to remain in the next few months as you were during the last 48 hours, would this be acceptable or unacceptable to you?"
The participant indicated a response of either "acceptable" or "unacceptable".
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Baseline, 12 weeks, 24 weeks
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Change From Baseline in Vectra Disease Activity Levels
Time Frame: Baseline, 12 weeks, 24 weeks
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The change from Baseline in Vectra disease activity levels was to be estimated.
The assessment measures serum protein biomarkers associated with RA.
It has a range from 1-100 with lower scores indicating the better outcome.
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Baseline, 12 weeks, 24 weeks
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Number of Participants With Positive Etanercept Anti-drug Antibody Status
Time Frame: Baseline, 12 weeks, 24 weeks
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Blood samples (6 mL) were collected at the baseline, Week 12, and Week 24 visits, or upon early withdrawal, to provide a minimum of 1 mL serum each for ETN ADA and ETN neutralizing antibody analyses.
Samples which were positive for ETN anti-drug antibodies were then also tested for ETN neutralizing antibodies.
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Baseline, 12 weeks, 24 weeks
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Number of Participants With Positive Etanercept Neutralizing Anti-drug Antibody Status
Time Frame: Baseline, 12 weeks, 24 weeks
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Blood samples (6 mL) were collected at the baseline, Week 12, and Week 24 visits, or upon early withdrawal, to provide a minimum of 1 mL serum each for ETN ADA and ETN neutralizing antibody analyses.
Samples which were positive for ETN anti-drug antibodies were then also tested for ETN neutralizing antibodies.
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Baseline, 12 weeks, 24 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2013
Primary Completion (Actual)
August 1, 2014
Study Completion (Actual)
August 1, 2014
Study Registration Dates
First Submitted
January 31, 2013
First Submitted That Met QC Criteria
January 31, 2013
First Posted (Estimate)
February 4, 2013
Study Record Updates
Last Update Posted (Estimate)
January 6, 2016
Last Update Submitted That Met QC Criteria
December 1, 2015
Last Verified
December 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gastrointestinal Agents
- Etanercept
Other Study ID Numbers
- B1801355
- 2012-003644-71 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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