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Study of Etanercept in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to Adalimumab or Infliximab Plus Methotrexate (SERUM)

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ClinicalTrials.gov Identifier: NCT01783015
Recruitment Status : Terminated (This study was prematurely terminated on June 25, 2014 due to lack of enrollment.)
First Posted : February 4, 2013
Results First Posted : January 6, 2016
Last Update Posted : January 6, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 31, 2013
First Posted Date  ICMJE February 4, 2013
Results First Submitted Date  ICMJE May 12, 2015
Results First Posted Date  ICMJE January 6, 2016
Last Update Posted Date January 6, 2016
Study Start Date  ICMJE September 2013
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2015)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2013)
Change from Baseline in Disease Activity Score Based on 28-joints Count (DAS28) [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2015)
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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".
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2013)
  • Change from Baseline in Disease Activity Score Based on 28-joints Count (DAS28) [ Time Frame: 24 weeks ]
  • Number of Participants With DAS28 <3.2 [ Time Frame: 12 weeks, 24 weeks ]
  • Number of Participants With DAS28 <2.6 [ Time Frame: 12 weeks, 24 weeks ]
  • Number of Participants Acheiving American College of Rheumatology 20% (ACR20) Response [ Time Frame: 12 weeks, 24 weeks ]
  • Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: 12 weeks, 24 weeks ]
  • Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: 12 weeks, 24 weeks ]
  • Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response [ Time Frame: 12 weeks, 24 weeks ]
  • Number of Participants Acheiving European League against Rheumatism (EULAR) Good and/or Moderate Response [ Time Frame: 12 weeks, 24 weeks ]
  • Number of Participants Acheiving Low Disease Activity or Remission Based on Clinical Disease Activity Index (CDAI) [ Time Frame: 12 weeks, 24 weeks ]
  • Number of Participants Acheiving Low Disease Activity or Remission Based on Simplified Disease Activity Index (SDAI) [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in Clinical Disease Activity Index (CDAI) [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in Simplified Disease Activity Index (SDAI) [ Time Frame: 12 weeks, 24 weeks ]
  • Change From Baseline in Number of Tender/Painful Joints [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in Number of Swollen Joints [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in Physician Global Assessment (PGA) of Disease Activity [ Time Frame: 12 weeks, 24 weeks ]
  • Change From Baseline in Subject Global Assessment of Disease Activity [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in Subject General Health [ Time Frame: 12 weeks, 24 weeks ]
  • Change From Baseline in Subject Pain [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in C-Reactive Protein (CRP) [ Time Frame: 12 weeks, 24 weeks ]
  • Change From Baseline in Health Assessment Questionnaire Disability and Discomfort Scales (HAQ-DI) [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in Euro Qol EQ-5 Dimensions Questionnaire (EQ-5D) [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in Short Form-36 Health Survey (SF-36) [ Time Frame: 12 weeks, 24 weeks ]
  • Change From Baseline in Patient Acceptable Symptom State (PASS) [ Time Frame: 12 weeks, 24 weeks ]
  • Change from Baseline in Vectra disease activity (DA) levels [ Time Frame: 12 weeks, 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Etanercept in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to Adalimumab or Infliximab Plus Methotrexate
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Etanercept
    Etanercept 50 mg once-weekly
  • Drug: Placebo
    Etanercept placebo once-weekly
Study Arms  ICMJE
  • Experimental: Group A
    Subjects who are mAb ADA positive
    Intervention: Drug: Etanercept
  • Experimental: Group B
    Subjects who are mAb ADA negative
    Intervention: Drug: Etanercept
  • Placebo Comparator: Group C
    Subjects who are mAb ADA positive
    Intervention: Drug: Placebo
  • Placebo Comparator: Group D
    Subjects who are mAb ADA negative
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 22, 2014)
16
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2013)
168
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 79 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   France,   Hong Kong,   Israel,   Russian Federation,   Spain
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT01783015
Other Study ID Numbers  ICMJE B1801355
2012-003644-71 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP