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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 24 March 2014
Main ID:  EUCTR2012-003644-71-NL
Date of registration: 07/01/2013
Prospective Registration: Yes
Primary sponsor: Pfizer Inc., 235 EAst 42nd Street, New York, NY 10017, United States
Public title: Randomized, Double-Blind, Placebo-Controlled Trial of etanercept plus methotrexate in monoclonal antibody (mAb) anti-TNF failure
Scientific title: A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Etanercept in Subjects with Rheumatoid Arthritis Who Have Had and Inadequate Response to Adalimumab or Infliximab Plus Methotrexate.
Date of first enrolment: 07/01/2013
Target sample size: 120
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003644-71
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4  
Phase: 
Countries of recruitment
Australia Belgium Chile Colombia France Hong Kong Israel Netherlands
Russian Federation Spain
Contacts
Name: ClinicalTrials.gov Call Center   
Address:  235 East 42nd Street NY 10017 New York United States
Telephone: +1800718 1021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Affiliation:  Pfizer Inc.
Name: ClinicalTrials.gov Call Center   
Address:  235 East 42nd Street NY 10017 New York United States
Telephone: +1800718 1021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Affiliation:  Pfizer Inc.
Key inclusion & exclusion criteria
Inclusion criteria:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Subject is literate and able to complete the protocol-specified questionnaires.

Period 1 Inclusion Criteria
In addition to the criteria in Section 4.1, subjects must meet all of the following inclusion criteria to be eligible for enrollment into Period 1 of the study:
1. Male or female = 18 years and <80 years of age at the time of consent.
2. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 12 weeks after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active (see Section 4.5 Life Style Guidelines)..
3. Met the 1987 ACR Revised Criteria for RA (see Appendix 1).
4. A history of inadequate efficacy response to at least a 6-month course of either infliximab or adalimumab with at least the last 4 weeks before the screening visit receiving a combination of either infliximab plus MTX or adalimumab plus MTX.
5. For subjects receiving infliximab, the last dose of infliximab must have been received = 6 weeks before the screening mAb ADA test.
6. For subjects receiving adalimumab, the last dose of adalimumab must have been taken = 11 days before the screening mAb ADA test.
7. Stable dose of oral MTX (10 mg QW to 25 mg QW) for =6 weeks before the baseline visit.
8. Active RA at the screening visit, defined as all of the following:
a. high-sensitivity C-reactive protein (hs-CRP) = 1.0 mg/L
b. = 6 tender joints based on the 28 joint assessment (see Section 7.1.5)
c. = 6 swollen joints based on the 28 joint assessment (see Section 7.1.5)
9. Active RA at the baseline visit, defined as all of the following:
a. = 6 tender joints based on the 28 joint assessment (see Section 7.1.5)
b. = 6 swollen joints based on the 28 joint assessment (see Section 7.1.5)
10.In the opinion of the investigator, subject is a reasonable candidate for treatment with etanercept plus MTX.
11.Either the subject or a designee must be capable (according to the investigator’s judgment) of administering the SC investigational product and must be able to store all investigational product under required storage conditions or must be able to come to the study site for administrations where the investigational product may be stored on behalf of the subject.
12.Active and latent tuberculosis (TB) must be ruled out by screening for TB in accordance with local country guidelines; subjects with recent exposure to active TB must be evaluated by a qualified physician to rule out TB (see Period 1 Exclusion Criteria 20).
13.Female subjects of childbearing potential per the investigator’s opinion must have negative urine pregnancy test results based on the screening visit and baseline visit tests (see Section 7.4.1 Pregna

Exclusion criteria:
Period 1:
1.Subjects who are investigational site staff members directly involved in conduct of trial and their family members, site staff members otherwise supervised by Investigator or subjects who are Pfizer employees directly involved in conduct of trial
2.ACR functional class IV
3.Prior treatment with etanercept any immunosuppressive biologic agent other than infliximab or adalimumab or both infliximab and adalimumab
4.Discontinuation of infliximab or adalimumab for primary reason other than inadequate efficacy response
5.Subjects receiving infliximab, dose >10 mg/kg every 4 weeks within 12 weeks before baseline
6.Subjects receiving adalimumab, dose >40 mg every other week within 12 weeks before baseline
7.Subject with known or suspected allergy, hypersensitivity or contraindication to MTX or its components or to etanercept, its excipients or other compounds related to this class of medication including biopharmaceutical proteins
8.Receipt >1 permitted non-biologic DMARD other than MTX or change in total daily dose of the additional permitted non-biologic DMARD within 4 weeks before baseline
9.Cyclophosphamide, cyclosporine or azathioprine within 6 months before baseline
10.Leflunomide without elimination procedure within 8 weeks before baseline or within 4 weeks of baseline if protocol-specified elimination procedure is followed.
11.Any invest. non-biologic drugs or devices within 12 weeks before baseline and/or during study B1801355
12.Non-biologic DMARDs other than those permitted during study or which are not listed under other excl. criteria within 8 weeks before baseline
13.Receipt >10 mg/day of oral prednisone (or equivalent) or change in dose within 2 weeks before baseline
14.IA or soft tissue corticosteroid injection or bolus IM or IV corticosteroids within 4 weeks before baseline
15.Receipt >1 NSAID or change in dose or type of NSAID within 2 weeks before baseline
16.Any live (attenuated) vaccines within 4 weeks before baseline
17.Any of following hematology or chemistry lab.abnormalities based on screening test results
a.WBC count =3.5 x 109/L
b.Hemoglobin level =85 g/L or =5.3 mmol/L
c.Hematocrit =27%
d.Platelet count =125 x 109/L
e.Serum creatinine level =175 µmol/L or =1.98 mg/dL
f.AST or ALT level =2 times upper limit of normal (X ULN)
18.Any other clinically significant lab. results or vital sign measurements
19.Active TB or evidence of untreated latent or active TB
20.Received TB chemoprophylaxis between the screening and baseline visits and has had ALT=2X ULN and/or AST=2X ULN during this period
21.Any infection assoc. with hospitalization and/or parenteral anti-infective agents within 4 weeks before baseline
22.Active infection at screening and/or baseline including systemic fungal infections
23.Any clinically relevant concurrent medical conditions, incl.:
a.Uncompensated congestive heart failure, Class III or IV heart failure or any episode of acute congestive heart failure within 6 months before screening
b.Uncontrolled hypertension
c.Myocardial infarction within 12 months before screening
d.Coronary artery bypass graft or percutaneous transluminal coronary angioplasty within 12 months before screening
e.Unstable angina pectoris within 6 months before screening
f.Presence or history of severe pulmonary disease requiring recurrent hospitalizations or supplemental oxygen
g.Presence or history of confirmed blood dyscrasias
h.Diagnosis of multiple sclerosis or other central or


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Rheumatoid Arthritis
MedDRA version: 16.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Intervention(s)

Trade Name: Enbrel
Product Name: Enbrel
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)
Main Objective: To compare the efficacy of etanercept to placebo in inadequate responders to infliximab or adalimumab plus methotrexate (MTX) in all subjects and in subjects who are anti-drug antibody positive (ADA+) to one of these monoclonal antibodies (mAbs).
Primary end point(s): Change from baseline in the disease activity score based on a 28 joint count (DAS28-CRP) at week 12
The primary study comparison is between etanercept 50 mg QW and placebo in all subjects, as determined by the change from baseline in DAS28-CRP scores at week 12.
The conditional primary study comparison is between etanercept 50 mg QW and placebo in subjects who are mAb ADA+, as determined by the change from baseline in DAS28-CRP scores at week 12.
Secondary Objective: • To assess the effect of ADA status on the efficacy of etanercept in inadequate responders to infliximab or adalimumab plus MTX
• To evaluate the safety of etanercept in inadequate responders to infliximab or adalimumab plus MTX.
Timepoint(s) of evaluation of this end point: 12 weeks
Secondary Outcome(s)
Secondary end point(s): Key Secondary Efficacy Endpoint
Change from baseline in the DAS28-CRP at week 24
The key secondary study comparison will be between subjects who are mAb ADA+ and mAb ADA- and are randomized to etanercept, as determined by the change from baseline in DAS28-CRP scores at week 24.

Additional Secondary Efficacy Endpoints
The following endpoints will be assessed at all timepoints unless otherwise noted:
• Change from baseline in DAS28-CRP
• DAS28-CRP < 3.2 and DAS28-CRP < 2.6
• American College of Rheumatology (ACR) 20, ACR50, ACR70, and ACR90
• European League Against Rheumatism (EULAR) good response and EULAR good/moderate response
• Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)
• Individual components of the ACR and DAS
• Etanercept ADA status (at week 12 and week 24, or upon early withdrawal). Samples which are positive for etanercept ADAs will also be tested for etanercept neutralizing antibodies.
• Vectra disease activity (DA) levels (at baseline, week 4, week 12, and week 24, or upon early withdrawal)
Timepoint(s) of evaluation of this end point: 24 weeks
Secondary ID(s)
2012-003644-71-ES
B1801355
Source(s) of Monetary Support
Pfizer Inc.
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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