A RANDOMIZED, DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF THE MAINTENANCE OF EFFICACY OF ETANERCEPT PLUS DMARD(S)COMPARED WITH DMARD(S) ALONE IN SUBJECTS WITH RHEUMATOID ARTHRITIS AFTER ACHIEVING AN ADEQUATE RESPONSE WITHETANERCEPT PLUS DMARD(S)
- Conditions
- Rheumatoid ArthritisMedDRA version: 16.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2011-005448-87-CZ
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 320
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team prior to subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
• 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.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Period 1 Inclusion Criteria - Subjects must meet all of the following inclusion criteria to be eligible for enrollment in Period 1 of the study:
1. Subject is 18 to 70 years of age at the time of consent (eligible on the day of the 18th birthday and ends the day prior to their 70th birthday).
2. The subject has a minimum 1 year history/diagnosis of RA based on the 1987 American College of Rheumatology (ACR) Revised criteria for RA.
3. Subject must have active RA as defined below despite methotrexate (MTX) therapy of =10 mg/wk for at least 12 weeks. The MTX dose must be stable for at least 4 weeks immediately prior to screening.
4. Active RA is defined as: (a) disease activity score based on a 28 joint count (DAS28 ESR) >=3.2 and at least 1 of the following at screening and baseline: =6 tender joint count (TJC) and =6 swollen joint count (SJC) or ESR=28 mm/hour and (b)HS-C-reactive protein (CRP) =3.5 mg/L at screening.
5. Subject has a functional status of Class I, II, or III as defined by 1991 ACR revised criteria.
6. Women of childbearing potential must have had a negative serum pregnancy test at screening. Additionally, a urine test must be performed prior to administration of first dose of study medication, Week 52 and Early Discontinuation visit
7. Male and female subjects of childbearing potential must agree to use a medically accepted highly effective method of contraception throughout the study and for 3 months 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.
8. Female subjects who are not of childbearing potential (ie, meet at least one of the following criteria):
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure or;
• Achieved post menopausal status, defined as: - cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum FSH level within the laboratory reference range for postmenopausal females.
9. Subject must be able to self inject drug or have a designee who can do so and be able to store study medication as required or must be able to come to study site where the study medication may be stored.
10. Active and latent TB must be ruled out by screening for tuberculosis (TB) in accordance with local country guideline. A Quantiferron test must be performed unless not available. Subjects with recent exposure to active TB must be evaluated by a qualified physician to rule out Tuberculosis.
11. Subject is literate and able to complete questionnaires.
Period 2 Inclusion Criteria - The subject must meet all of the following criteria to be randomized into Period 2 of the study:
1. Subject has completed Period 1 of the study.
2. Subject has a DAS28 <3.2 at Week 2
Period 1 Exclusion Criteria:
1. Subjects, who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Subjects who used any of the following systemic treatments during washout periods:
(a) Oral corticosteroid dose of prednisone >7.5 mg/day or a change in dose w/in 28 days of baseline (BL)
(b)Treatment with >1 NSAID w/in 14 days at BL
(c) MTX dose > 25 mg/week, or change in dose w/in 28 days of BL
(d) Subjects allowed to continue the following: SZ, HCQ, & LEF. All other non-biologic DMARDs & biologic DMARDs must have been discontinued > 2 months prior to Week 0
(e) Any biologic B cell depleting agent w/in 2 years of Week 0.
3. known or suspected allergy, hypersensitivity, or contraindication to ETN, its excipients, or other compounds related to this class of medication.
4. received any live vaccine w/in 4 weeks prior to BL.
5. abnormal hematology or blood chemistry profile during screening (SC) period. If SC lab tests are abnormal, repeat to confirm results. Results from SC visit must be available at BL visit. BL lab results are not required prior to first dose, but if results subsequently show that the subject does not meet these exclusion levels & is confirmed upon retest, subject must be withdrawn from study.
• White blood cell (WBC) count =3.5 x 10 to the power of 9/L;
• Hemoglobin level =85 g/L or =5.3 mmol/L;
• Hematocrit =27%;
• Platelet count =125 x 10 to the power of 9/L;
• Serum creatinine level =175 µmol/L (=1.98 mg/dL);
• AST or ALT level =2 times the lab’s upper limit of normal.
6. active & latent TB: Follow local guidelines for appropriate TB SC in the setting of anti-TNF therapy, including a minimum of a chest radiograph & objective TB testing. A PPD of >5 mm should be considered positive for TB unless local guidelines for testing of immunocompromized (subjects with RA) subjects is available & different. (a) Subjects with current or recent (w/in 2 years of SC) active TB infection are excluded (b) Subjects with history of active TB > 2 years ago & with documentation of completing an adequate regimen of anti TB therapy may be considered for enrollment after discussion with sponsor (c)Subjects with known latent TB infection may be allowed only if local guidelines are followed for prophylactic therapy & if TB chemoprophylaxis has been adequately completed or initiated at least 4 weeks prior to Week 0 visit.
7. received TB chemoprophylaxis during SC &has had ALT and/or AST >2x upper limit of normal [ULN] during this period. Subjects diagnosed with TB & started chemoprophylaxis during SC period, additional blood samples for ALT & AST must be drawn between 3-4 weeks after initiating chemoprophylaxis. Results need to be reviewed prior to randomization.
8. serious infection w/in 1 month prior to Week 0 visit.
9. active infection at time of the SC visit and/or Week 0 visit, including systemic fungal infections.
10. clinically relevant concurrent medical conditions.
11. anticipating surgical procedure during study period.
12. participating in other studies involving investigational drug(s) (Phases 1-4) w/in 3 months of study.
13. pregnant females or those with a positive pregnancy test result at SC or BL; breastfeeding females; males & females of childbearing potential who are unwilling or unable to use a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method