A 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 WITH ETANERCEPT PLUS DMARD(S)

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2011-005448-87-HU
• Date of registration: 21/03/2012
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: A 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 WITH ETANERCEPT PLUS DMARD(S)
• Scientific title: 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 WITH ETANERCEPT PLUS DMARD(S)
• Date of first enrolment: 14/05/2012
• Target sample size: 320
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005448-87
• 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: yes Other trial design description: Note: period 1 is open label If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Brazil, China, Colombia, Czech Republic, Egypt, Hungary, India, Malaysia, Mexico, Philippines, Poland, Romania, Russian Federation, Saudi Arabia, Slovakia, South Africa, Taiwan, Thailand, Turkey, Ukraine, United Arab Emirates

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Center
• 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 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)C-reactive protein (CRP) =7.0 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 hysterectomy or bilateral oophorectomy;
• Have medically confirmed ovarian failure or;
• Are medically confirmed to be post menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause.
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 24.
3. Subject must be willing to continue stable dose of all RA medication subject is using at Week 24 through W
Exclusion criteria:
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 highly effective method of
c

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 14.1 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® 50 mg Solution for Injection in Pre-filled Syringe
Pharmaceutical Form: Solution for injection
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 injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Proportion of subjects who remained in LDA (DAS28 ESR<3.2) at Week 52, among those who have achieved LDA at Week 24.

Timepoint(s) of evaluation of this end point: 52 weeks

Main Objective: To compare the maintenance of efficacy of the combination of ETN 50 mg once weekly plus MTX (± other DMARDs) therapy with that of MTX (± other DMARDs) at Week 52 in subjects with moderately to severely active RA who have achieved LDA (DAS28 ESR<3.2) after 24 weeks of therapy with open label ETN 50 mg once weekly plus MTX (± other DMARDs) in a treat to target paradigm.

Secondary Objective: • To assess the clinical efficacy of the treatment regimens during Periods 1 and 2.

• To assess the maintenance of remission (DAS28<2.6) at Week 52 in those subjects who achieved remission after 24 weeks therapy with open label ETN 50 mg once weekly plus MTX (+ DMARDs).

• To assess the improvement in quality of life achieved and maintained by the treatment regimens over 52 weeks.

• To assess the improvement in physical function achieved and maintained by treatment regimens over 52 weeks.

• To assess the safety of the treatment regimens over 52 weeks.

Secondary Outcome(s)

Secondary end point(s): • Proportion of subjects who remained in remission (DAS28 ESR<2.6) at Week 52, among those who have achieved remission at Week 24.
• Proportion of subjects in LDA or remission (by both DAS28 ESR and DAS28 CRP scores) at each visit during Period 1 & Period 2.
• Change from baseline in the DAS28 (-CRP and ESR) score at each visit during Period 1 and Period 2.
• Time-to-flare or loss of efficacy (loss of LDA plus =0.6 unit worsening in DAS28 ESR score) during Period 2.
• Proportion of subjects achieving European League Against Rheumatism (EULAR) good and or moderate responses (by both DAS28 ESR and DAS28 CRP scores) at each visit during Period 1 and Period 2.
• Proportion of subjects achieving LDA or remission at each visit during Period 1 and 2 based on CDAI and SDAI each visit during Period 1 and 2.
• Change of CDAI and SDAI at each visit during Period 1 and 2.
• Proportion of subjects achieving ACR 20, ACR 50, ACR 70 and ACR 90 (by 66/68 joint counts) during Period 1 and Period 2 at each visit.
• Change in the tender and swollen joint counts at each visit during Period 1 and Period 2 (using 28 joint count as well as 66/68 joint counts).
• Change in the Physician Global Assessment at each visit during Period 1 and Period 2.
• Change in the Subject Global Assessment, including morning stiffness (measured in minutes) at each visit during Period 1 and Period 2.
• Change in the Subject General Health visual analog scale (VAS), and Pain VAS at each visit during Period 1 and Period 2.
• Change in CRP and ESR at each visit during Period 1 & Period 2.

Timepoint(s) of evaluation of this end point: Throughout the study and at 52 weeks

Secondary ID(s)

B1801315

Source(s) of Monetary Support

Pfizer Inc.