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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Australia
    • Western Australia
      • Victoria Park, Western Australia, Australia, 6100
        • RK Will Pty Ltd
  • Belgium
      • Bruxelles, Belgium, 1200
        • Cliniques Universitaires Saint-Luc / Service de Rhumatologie
  • France
      • Montpellier, France, 34295 cedex 5
        • Hopital Lapeyronie
  • Hong Kong
      • Tseung Kwan O, NT, Hong Kong
        • Tseung Kwan O Hospital
    • New Territories
      • Tseung Kwan O, New Territories, Hong Kong
        • Tseung Kwan O Hospital
  • Israel
      • Haifa, Israel, 31048
        • Bnai Zion Medical Ctr Pharmacy
      • Kfar Saba, Israel, 44281
        • Meir Medical Center pharmacy
  • Russian Federation
      • Izhevsk, Russian Federation, 426063
        • LLC "Alliance Biomedical - Russian Group"
      • Kazan, Russian Federation, 420103
        • LLC Research Medical Complex "Your Health" based on City Clinical Hospital #7
      • Moscow, Russian Federation, 115522
        • Scientific Institute of Rheumatology of Russian Academy of Medical Science
      • Moscow, Russian Federation, 129301
        • GBOU VPO Moscow State University of Medicine and Dentistry
  • Spain
      • Barcelona, Spain, 08025
        • Hospital de la santa Creu i San Pau
      • Málaga, Spain, 29009
        • Hospital Regional Universitario Carlos Haya. Hospital Civil
      • Málaga, Spain, 29010
        • Hospital Regional Universitario Carlos Haya.
      • Sevilla, Spain, 41010
        • Hospital Infanta Luisa

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Met the 1987 ACR Revised Criteria for RA
  2. A history of inadequate response to infliximab or adalimumab in combination with methotrexate.
  3. A stable dose of oral methotrexate for at least 6 weeks before the baseline visit.

Exclusion Criteria:

  1. ACR functional class IV
  2. Prior treatment with etanercept; both infliximab and adalimumab; or any immunosuppressive biologic agent other than infliximab or adalimumab.
  3. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group A
Subjects who are mAb ADA positive
Drug: Etanercept
Etanercept 50 mg once-weekly
Experimental: Group B
Subjects who are mAb ADA negative
Drug: Etanercept
Etanercept 50 mg once-weekly
Placebo Comparator: Group C
Subjects who are mAb ADA positive
Drug: Placebo
Etanercept placebo once-weekly
Placebo Comparator: Group D
Subjects who are mAb ADA negative
Drug: Placebo
Etanercept placebo once-weekly

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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).
Baseline, 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in the DAS28 at Week 24
Time Frame: Baseline, 24 weeks
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).
Baseline, 24 weeks
Number of Participants With DAS28 <3.2
Time Frame: 12 weeks, 24 weeks
Number of participants with DAS28 <3.2. A score of < 3.2 implied low disease activity.
12 weeks, 24 weeks
Number of Participants With DAS28 <2.6
Time Frame: 12 weeks, 24 weeks
Number of Participants with DAS28 <2.6. A DAS28 < 2.6 implies remission.
12 weeks, 24 weeks
Number of Participants Achieving American College of Rheumatology 20% (ACR20) Response
Time Frame: 12 weeks, 24 weeks
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.
12 weeks, 24 weeks
Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Time Frame: 12 weeks, 24 weeks
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.
12 weeks, 24 weeks
Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Time Frame: 12 weeks, 24 weeks
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.
12 weeks, 24 weeks
Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response
Time Frame: 12 weeks, 24 weeks
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.
12 weeks, 24 weeks
Number of Participants Achieving European League Against Rheumatism (EULAR) Good and/or Moderate Response.
Time Frame: 12 weeks, 24 weeks
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.
12 weeks, 24 weeks
Number of Participants Achieving Low Disease Activity or Remission Based on Clinical Disease Activity Index (CDAI)
Time Frame: 12 weeks, 24 weeks
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.
12 weeks, 24 weeks
Number of Participants Achieving Low Disease Activity or Remission Based on Simplified Disease Activity Index (SDAI).
Time Frame: 12 weeks, 24 weeks
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.
12 weeks, 24 weeks
Change From Baseline in CDAI
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change From Baseline in SDAI.
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change From Baseline in Number of Tender/Painful Joints
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change From Baseline in Number of Swollen Joints
Time Frame: Baseline, 12 weeks, 24 weeks
Change from Baseline in the number of swollen joints including shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees was to be calculated.
Baseline, 12 weeks, 24 weeks
Change From Baseline in Physician Global Assessment of Disease Activity
Time Frame: Baseline, 12 weeks, 24 weeks
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).
Baseline, 12 weeks, 24 weeks
Change From Baseline in Subject Global Assessment of Disease Activity
Time Frame: Baseline, 12 weeks, 24 weeks
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).
Baseline, 12 weeks, 24 weeks
Change From Baseline in Subject General Health VAS.
Time Frame: Baseline, 12 weeks, 24 weeks
Subject General Health VAS assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).
Baseline, 12 weeks, 24 weeks
Change From Baseline in Subject Pain
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change From Baseline in CRP
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change From Baseline in Health Assessment Questionnaire Disability and Discomfort Scales (HAQ-DI)
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change From Baseline in Euro Quality of Life (Qol) EQ-5 Dimensions Questionnaire (EQ-5D)
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change From Baseline in Short Form-36 Health Survey (SF-36)
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change From Baseline in Patient Acceptable Symptom State (PASS)
Time Frame: Baseline, 12 weeks, 24 weeks
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".
Baseline, 12 weeks, 24 weeks
Change From Baseline in Vectra Disease Activity Levels
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Number of Participants With Positive Etanercept Anti-drug Antibody Status
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Number of Participants With Positive Etanercept Neutralizing Anti-drug Antibody Status
Time Frame: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

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.

Helpful Links

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 31, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 4, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 6, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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