Study Comparing The Effect On Disease Activity When Reducing Or Discontinuing Etanercept In Subjects With RA

Rheumatoid Arthritis Clinical Trial

— DOSERA  

Official title:

Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Subjects Who Have Achieved a Stable Low Disease Activity-state (DOSERA)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00858780
• Other study ID #: 0881K1-4500
• Secondary ID: B1801016
• Status: Completed
• Phase: Phase 4
• First received: March 6, 2009
• Last updated: August 30, 2013
• Start date: January 2009
• Est. completion date: June 2012

Study information

• Verified date: August 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines AgencyDenmark: Ethics CommitteeFinland: Ethics CommitteeFinland: Nat
• Study type: Interventional

Clinical Trial Summary

This study involves Rheumatoid Arthritis patients in regular clinical setting who are already on etanercept treatment and are in remission or in a low disease activity (LDA) state, and is intended to identify parameters that can serve as guidance in clinical settings. This study will consider the clinical and radiographic course in subjects when etanercept treatment is tapered or discontinued, and analyze the subjects' experience of disease worsening and the predictive values of clinical parameters, serum biomarkers and imaging on the clinical and radiographic course in different treatment groups. The effect of re-treatment with etanercept at treatment failure will also be studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Subject has a current DAS28 equal to or less than 3.2.

• Subject is currently receiving treatment with etanercept, either 25 mg twice weekly or 50 mg once weekly, for a minimum of 14 months at baseline

• Subject is currently receiving oral, sc or intramuscular methotrexate once weekly, 7.5 mg/week to 25 mg/week and at a stable dose for a minimum of 4 months at baseline.

Exclusion Criteria:

• Subject has earlier had an attempt of discontinuing etanercept for reasons of remission or low disease activity state.

• Subject has received any disease-modifying anti-rheumatic drug, other than methotrexate, within one month before baseline.

• Subject has had a dose of prednisone (or equivalent) >7.5 mg/day or has received intra-articular, intravenous, intramuscular, or subcutaneous corticosteroid within one month of baseline.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Etanercept
50 mg etanercept once weekly + methotrexate
• Etanercept
25mg etanercept once weekly + methotrexate
• Placebo
Placebo comparator once weekly + methotrexate

Locations

Country	Name	City	State
Denmark	Pfizer Investigational Site	Glostrup
Denmark	Pfizer Investigational Site	Hellerup
Finland	Pfizer Investigational Site	Helsinki
Finland	Pfizer Investigational Site	Jyvaskyla
Hungary	Pfizer Investigational Site	Gyula
Hungary	Pfizer Investigational Site	Szombathely
Hungary	Pfizer Investigational Site	Veszprem
Iceland	Pfizer Investigational Site	Reykjavik
Norway	Pfizer Investigational Site	Bergen
Norway	Pfizer Investigational Site	Lillehammer
Norway	Pfizer Investigational Site	Oslo
Sweden	Pfizer Investigational Site	Lund
Sweden	Pfizer Investigational Site	Malmo
Sweden	Pfizer Investigational Site	Stockholm
Sweden	Pfizer Investigational Site	Stockholm
Sweden	Pfizer Investigational Site	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Denmark,  Finland,  Hungary,  Iceland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participant Who Were Non-Failures	A participant was considered as non-failure if the calculated DAS28 <=3.2 at all visits or if the calculated DAS28 >3.2, the increase of calculated DAS28 from randomization (Week 0): was <0.6 at all visit or was >=0.6 but <1.2 on no more than 1 consecutive visit. Percentage of participants who were non-failures calculated based on DAS28 and disease progression as determined by investigator or participant.	Week 48	No
Secondary	Time to Treatment Failure (TTF)	TTF (in weeks): (date of failure minus date of randomization) divided by 7. Date of failure was ordinary visit date or extra visit date in case of failure (extra visit was within 2 weeks from the date a participant experienced significant disease progression between visits and wanted to withdraw from Period 2), or date of withdrawal due to disease progression. Participants who did not have a treatment failure were censored at their last evaluation visit. Participants who withdrew from the study prematurely and did not have a treatment failure were censored on the date of their withdrawal.	Randomization (Week 0) up to date of failure, withdrawal due to disease progression or last evaluation visit (Week 48)	No
Secondary	Percentage of Participants With Remission or Low Disease Activity (LDA)	Participants who had DAS28 less than or equal to (<=) 3.2 were considered in remission or LDA state.	Baseline (Week -8), Week -4, Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Percentage of Visits During Which Participants Were in Remission or Low Disease Activity State	Participants who had DAS28 <=3.2 were considered in remission or LDA state. Percentage of visits during which a participant was in remission or LDA state was calculated as number of visits in which participant was in remission or LDA divided by total number of visits multiplied by 100.	Randomization (Week 0) up to Week 48	No
Secondary	Disease Activity Score Based on 28-Joint Count (DAS28) at Randomization	DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 implied low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity and less than (<) 2.6=remission.	Randomization (Week 0)	No
Secondary	Change From Randomization in Disease Activity Score Based on 28-Joint Count (DAS28) at Week 6, 12, 18, 24, 30, 36, 42, and 48	DAS28 calculated from SJC and PJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity and <2.6=remission.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Change From Randomization in Tender Joints Count (TJC) at Week 6, 12, 18, 24, 30, 36, 42, and 48	Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from randomization indicates an improvement.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Change From Randomization in Swollen Joints Count (SJC) at Week 6, 12, 18, 24, 30, 36, 42, and 48	Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. A negative value in change from randomization indicates an improvement.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Change From Randomization in Physician Global Assessment (PGA) of Disease Activity at Week 6, 12, 18, 24, 30, 36, 42, and 48	PGA of disease activity was measured on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), with 0 mm = no disease activity and 100 mm = extreme disease activity.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Change From Randomization in Participant Global Assessment (PtGA) of Disease Activity at Week 6, 12, 18, 24, 30, 36, 42, and 48	Participants assessed the overall activity of their rheumatoid arthritis (RA) on a 0 to 100 mm VAS, where 0 mm = no disease activity and 100 mm = extreme disease activity.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Participant General Health Visual Analog Scale (VAS) at Randomization	Participants answered "in general how would you rate your health over the last 2-3 weeks?" Participants responded by using a 0 to 100 mm VAS, where 0 mm = very well and 100 mm = extremely bad.	Randomization (Week 0)	No
Secondary	Change From Randomization in Participant General Health Visual Analog Scale (VAS) at Week 6, 12, 18, 24, 30, 36, 42, and 48	Participants answered "in general how would you rate your health over the last 2-3 weeks?" Participants responded by using a 0 to 100 mm VAS, where 0 mm = very well and 100 mm = extremely bad.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Participant Pain Visual Analog Scale (VAS) at Randomization	Participants indicated the amount of pain experience during the last 2-3 days by marking a vertical line on 100 mm VAS. Intensity of pain range: 0 = no pain to 100 = pain as bad as it could be.	Randomization (Week 0)	No
Secondary	Change From Randomization in Participant Pain Visual Analog Scale (VAS) at Week 6, 12, 18, 24, 30, 36, 42, and 48	Participants indicated the amount of pain experience during the last 2-3 days by marking a vertical line on 100 mm VAS. Intensity of pain range: 0 = no pain to 100 = pain as bad as it could be.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Change From Randomization in Morning Stiffness Duration at Week 6, 12, 18, 24, 30, 36, 42, and 48	Duration of morning stiffness: Time elapsed when participant woke up in morning and was able to resume normal activities without stiffness in minutes. The duration of morning stiffness was determined by asking the following questions: 1) Over the last 2 days, when did you wake in the morning? 2) Over the last 2 days, when were you able to resume your normal activities without stiffness? Increase in stiffness duration from randomization represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Change From Randomization in Erythrocyte Sedimentation Rate (ESR) at Week 6, 12, 18, 24, 30, 36, 42, and 48	ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 millimeter per hour (mm/hour). A higher rate is consistent with inflammation.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Change From Randomization in C-Reactive Protein (CRP) Level at Week 6, 12, 18, 24, 30, 36, 42, and 48	The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is <10 milligram per liter (mg/L). A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48	No
Secondary	Change From Randomization in Modified Total Sharp Score (mTSS) at Week 48	mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at randomization. An increase in mTSS from randomization represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Randomization (Week 0), Week 48	No
Secondary	Magnetic Resonance Imaging (MRI) Findings at Randomization	MRI of hand/wrist of dominant hand scored for signs of synovitis (S-score), bone edema(O-score), bone erosions (E-score) as per outcome measures in RA clinical trials (OMERACT). S-score:0(normal)-3(severe) for distal radioulnar,radiocarpal,intercarpal-carpometacarpal,second-fifth metacarpophalangeal joints, total score(TS)0-21, higher score(HS)=severe synovitis. O-score:0(no volume increment)-3(100% volume increment) in 23 hand/wrist joints, TS 0-69, HS=more edema. E-score:0(no volume occupied by erosion)-10(100% volume occupied by erosion) in 23 hand/wrist joints, TS 0-230, HS=more erosion.	Randomization (Week 0)	No
Secondary	Change From Randomization in Magnetic Resonance Imaging (MRI) Findings (S-Score) at Week 12	MRI of hand/wrist of dominant hand was scored for signs of synovitis (S-score), bone edema (O-score), and bone erosions (E-score) as per OMERACT. S-score: 0 (normal) to 3 (severe) for each of distal radioulnar, radiocarpal, intercarpal-carpometacarpal, second to fifth metacarpophalangeal joints; total score 0 to 21, higher score=severe synovitis.	Randomization (Week 0), Week 12	No
Secondary	Change From Randomization in Magnetic Resonance Imaging (MRI) Findings (O-Score, E-Score) at Week 12	MRI of hand/wrist of dominant hand was scored for signs of synovitis (S-score), bone edema (O-score), and bone erosions (E-score) as per OMERACT. O-score: 0 (no volume increment) to 3 (100% volume increment) in 23 hand/wrist joints; total score 0 to 69, higher scores=more edema. E-score: 0 (no volume occupied by erosion) to 10 (100% volume occupied by erosion) in 23 hand/wrist joints; total score 0 to 230, higher scores=more erosion.	Randomization (Week 0), Week 12	No
Secondary	Percentage of Participants in Treatment Failure for Each Potentially Predictor Variable at Randomization	Percentage of participants who were treatment failure over 48 weeks as per potentially predictor variables (at randomization) are reported: number of swollen joints/tender joints, DAS28, PGA, PtGA, participant general health VAS, participant pain VAS, clinical disease activity index (CDAI), simplified disease activity index (SDAI), ESR (mm/hour), plasma CRP (mg/L), sensitive serum CRP (mg/L), anti- cyclic citrullinated peptide (anti CCP, units/mL), cartilage oligomeric matrix protein (COMP, units/liter), S-score, O-score, E-score, Joint space narrowing score, erosion score, and mTSS.	Randomization (Week 0) up to Week 48	No

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