Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT00195494
• Recruitment Status: Completed
• First Posted: September 19, 2005
• Results First Posted: September 5, 2012
• Last Update Posted: September 5, 2012
• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Information provided by (Responsible Party): Wyeth is now a wholly owned subsidiary of Pfizer

Tracking Information

• First Submitted Date: September 13, 2005
• First Posted Date: September 19, 2005
• Results First Submitted Date: March 31, 2009
• Results First Posted Date: September 5, 2012
• Last Update Posted Date: September 5, 2012
• Study Start Date: November 2004
• Actual Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 1, 2012)

• The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6. [ Time Frame: 12 months ]
  Effects of the combination of etanercept and methotrexate to methotrexate alone on clinical disease activity. DAS28 scale 0 - 10, 3.2 or lower showing controlled disease while 5.1 implies active disease.
• Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5. [ Time Frame: 12 months ]
  The (van der Heijde) modified total Sharp score (mTSS) is the sum of scores for erosions (range 0-280) and joint space narrowings (range 0-168) and thus has a total range of (0 - 448 ), where zero is the best score , indicating no damage.

Original Primary Outcome Measures (submitted: September 13, 2005)

• To compare the effects of the combination of etanercept and methotrexate to
• methotrexate alone on radiographic change and clinical disease activity in
• subjects with active early rheumatoid arthritis over 12 months.

Current Secondary Outcome Measures (submitted: August 1, 2012)

Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death [ Time Frame: 12 and 24 months ]

Safety report for entire trial where participants reported a serious adverse event that led to death.

Original Secondary Outcome Measures (submitted: September 13, 2005)

• Evaluate the safety of each treatment group over 24 months; compare the effects
• of the combination of ETN and MTX to MTX alone on radiographic change and
• clinical disease activity over 12 months and 24 months

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

Descriptive Information

• Brief Title: Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis
• Official Title: A 24-Month,Randomized,Double-Blind,Two-Period Study to Evaluate the Efficacy and Safety of the Combination of Etanercept and Methotrexate and Methotrexate Alone in Subjects With Early Rheumatoid Arthritis
• Brief Summary: To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change and clinical disease activity in subjects with early RA over 12 months.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• Drug: Etanercept

  Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2

  Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2

  Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2

• Drug: Methotrexate

  Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2

  Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2

  Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2

  Group 2b: Oral Methotrexate weekly for both Periods 1 and 2

• Drug: Placebo

  Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2

  Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2

Study Arms

• Active Comparator: 1a
  Etanercept + Methorexate for Period 1 (first 12 months) and Period 2 (Second 12 months)
  Interventions:

  • Drug: Etanercept
  • Drug: Methotrexate
• Active Comparator: 1b
  Etanercept + Methotrexate for Period 1 (First 12 months) and Etanercept alone for Period 2 (Second 12 months)
  Interventions:

  • Drug: Etanercept
  • Drug: Methotrexate
  • Drug: Placebo
• Active Comparator: 2a
  Methotrexate alone in Period 1 (First 12 months) and etanercept + Methotrexate in Period 2 (Second 12 months)
  Interventions:

  • Drug: Etanercept
  • Drug: Methotrexate
  • Drug: Placebo
• Active Comparator: 2b
  Methotrexate alone in Period 1 (First 12 months) and Methotrexate alone in Period 2 (Second 12 months)
  Intervention: Drug: Methotrexate

Publications *

• Fleischmann RM, van der Heijde D, Gardiner PV, Szumski A, Marshall L, Bananis E. DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable. RMD Open. 2017 Jan 30;3(1):e000382. doi: 10.1136/rmdopen-2016-000382. eCollection 2017.
• Gallo G, Brock F, Kerkmann U, Kola B, Huizinga TW. Efficacy of etanercept in combination with methotrexate in moderate-to-severe rheumatoid arthritis is not dependent on methotrexate dosage. RMD Open. 2016 Apr 21;2(1):e000186. doi: 10.1136/rmdopen-2015-000186. eCollection 2016.
• Zhang W, Sun H, Emery P, Sato R, Singh A, Freundlich B, Anis AH. Does achieving clinical response prevent work stoppage or work absence among employed patients with early rheumatoid arthritis? Rheumatology (Oxford). 2012 Feb;51(2):270-4. doi: 10.1093/rheumatology/ker189. Epub 2011 Jun 29.
• Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig AS, Freundlich B. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008 Aug 2;372(9636):375-82. doi: 10.1016/S0140-6736(08)61000-4. Epub 2008 Jul 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 1, 2012): 542
• Original Enrollment (submitted: September 13, 2005): 540
• Actual Study Completion Date: March 2008
• Actual Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Satisfies the 1987 ACR Revised Criteria for Rheumatoid Arthritis
• Has RA greater than or equal to 3 months and less than or equal to 2 years

Exclusion Criteria:

• Received any previous treatment with MTX
• Received any previous treatment with ETN or other tumour necrosis factor antagonist

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: United States

Administrative Information

• NCT Number: NCT00195494
• Other Study ID Numbers: 0881A-101548
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
• Study Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor; Wyeth is now a wholly owned subsidiary of Pfizer

• PRS Account: Wyeth is now a wholly owned subsidiary of Pfizer
• Verification Date: August 2012