Formation of Antibodies and Subsequent Prediction of Clinical Response in Patients With Rheumatoid Arthritis Treated With Four TNF Blocking Agents

• ClinicalTrials.gov Identifier: NCT01691014
• Recruitment Status: Terminated
• First Posted: September 24, 2012
• Results First Posted: December 29, 2016
• Last Update Posted: December 29, 2016
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 12, 2012
• First Posted Date: September 24, 2012
• Results First Submitted Date: November 1, 2016
• Results First Posted Date: December 29, 2016
• Last Update Posted Date: December 29, 2016
• Study Start Date: April 2013
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 1, 2016)

• Number of Participants With Anti-drug Antibodies Formation Levels 6 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab [ Time Frame: Month 6 ]
  Anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay.
• Number of Participants With Presence of Active Drugs in Serum 6 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab [ Time Frame: Month 6 ]
  Presence of active drugs in serum 6 months after treatment with Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay.

• Original Primary Outcome Measures (submitted: September 21, 2012): Anti-drug antibody levels and serum levels of active drug 6 months after initiation of treatment with ADA, ETA, GOL or IFX [ Time Frame: 6 months ]
• Change History: Complete list of historical versions of study NCT01691014 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: November 1, 2016)

• Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Disease Activity Score 28 (DAS28) 12 Months After Initiation of Treatment [ Time Frame: Month 6, 12 ]
  Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept, Infliximab and DAS28 was to be analyzed using Pearson and Spearman correlations across and within each of the four treatment groups. DAS28-4 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joint count, C-reactive protein (CRP) in milligram per liter (mg/L) and participant global assessment (PGA) of disease activity (participant rated arthritis activity assessment with total score ranging from 0 [good condition] to 10 [worst condition]; higher score indicates worse condition). DAS28-4 total score range: 0 (no disease activity) to 9.4 (maximum disease activity), higher score indicates more disease activity.
• Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Health Assessment Questionnaire (HAQ) 12 Months After Initiation of Treatment [ Time Frame: Month 6, 12 ]
  Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept, Infliximab and HAQ scores was to be analyzed using Pearson and Spearman correlations across and within each of the four treatment groups. HAQ was a self-reported, valid assessment of functional disability in rheumatoid arthritis based on ability of participants to perform daily activities. HAQ total score range: 0 (normal functioning) to 3 (worst functioning), where higher score indicates worse functioning.
• Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Cessation of Therapy Between Month 6 and 12 Visits [ Time Frame: Month 6, 12 ]
  Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab and cessation of therapy was to be analyzed. Cessation of therapy between month 6 and month 12 was the time to withdrawal from study due to either adverse events or lack of effect between the 6 month visit and the 12 month visit.
• Number of Participants With Anti-drug Antibodies Levels 3 and 12 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab [ Time Frame: Month 3, 12 ]
  Anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay.
• Correlation Between the Formation of Anti-drug Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab and Concomitant Methotrexate Treatment [ Time Frame: Month 12 ]
  Association between formation of anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab and concomitant Methotrexate treatment (weekly dose of 7.5 milligram) was to be analyzed.
• Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 [ Time Frame: Month 3, 6, 12 ]
  DAS28-4 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joint count, C-reactive protein (CRP) in milligram per liter (mg/L) and participant global assessment (PGA) of disease activity (participant rated arthritis activity assessment with total score ranging from 0 [good condition] to 10 [worst condition]; higher score indicates worse condition). DAS28-4 total score range: 0 (no disease activity) to 9.4 (maximum disease activity), higher score indicates more disease activity. DAS28-4 (CRP) less than or equal to (<=) 3.2 implied low disease activity and greater than (>) 3.2 to 5.1 implied moderate to high disease activity.
• Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 [ Time Frame: Baseline, Month 3, 6, 12 ]
  HAQ was a self-reported, valid assessment of functional disability in rheumatoid arthritis based on ability of participants to perform daily activities. HAQ total score range: 0 (normal functioning) to 3 (worst functioning), where higher score indicates worse functioning.

Original Secondary Outcome Measures (submitted: September 21, 2012)

• Description of the association between the formation of antibodies to ADA, ETA, GOL and IFX 6 months after initiation of treatment with ADA, ETA, GOL or IFX and the clinical response 12 months after initiation of treatment [ Time Frame: 12 months ]
• Anti-drug antibody levels 12 months after initiation of treatment with ADA, ETA, GOL or IFX [ Time Frame: 12 months ]
• Description of the association between the formation of anti-drug antibodies and concomitant methotrexate (MTX) [ Time Frame: 12 months ]
• Description of the association between pauses in TNF-α blocking treatment and formation of anti-drug antibodies [ Time Frame: study period (2 years) ]
• DAS 28 3, 6 and 12 months after initiation of treatment with ADA, ETA, GOL or IFX [ Time Frame: 3, 6 and 12 months ]
• HAQ score at baseline, 3, 6 and 12 months after initiation of treatment with ADA, ETA, GOL or IFX [ Time Frame: 3, 6 and 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Formation of Antibodies and Subsequent Prediction of Clinical Response in Patients With Rheumatoid Arthritis Treated With Four TNF Blocking Agents
• Official Title: Formation Of Antibodies And Subsequent Prediction Of Clinical Response In Patients With Rheumatoid Arthritis Treated With Four Tnf Blocking Agents
• Brief Summary: The rationale for this study is to further explore if development of antibodies against TNF-α blocking agents is associated with reduced clinical effect/worsened clinical outcome. An important aspect of the study is to carry out an exploratory analysis of the immunogenicity of the 4 recommended TNF-α blockers in the treatment of RA in Denmark, using the same cell-based assay.
• Detailed Description: no sampling
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: patients with Rheumatoid Arthritis (RA)
• Condition: Rheumatoid Arthritis (RA)

Intervention

Other: non-interventional study

Study with 4 arms/groups with 36 patients per group. In total 144 patients.

Study Groups/Cohorts

• adalimumab
  Intervention: Other: non-interventional study
• Etanercept
  Intervention: Other: non-interventional study
• infliximab
  Intervention: Other: non-interventional study
• Certolizumab
  Intervention: Other: non-interventional study

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 1, 2016): 79
• Original Estimated Enrollment (submitted: September 21, 2012): 144
• Actual Study Completion Date: January 2015
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject fulfils criteria for Rheumatoid Arthritis (RA) according to ACR or EULAR criteria.
• Subjects who are planned to start treatment with ADA, ETA, CER or IFX
• Subjects taking a minimum weekly dose of 7.5 mg of methotrexate

Exclusion Criteria:

• Patients with compliance problems
• Patients who have difficulties in reading and understanding local language
• Patients with Juvenile Idiopathic Arthritis (JIA)
• Azathioprine or cyclophosphamide treatment within 6 months before entering into the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT01691014
• Other Study ID Numbers: B1801347
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2016