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Study of Etanercept Monotherapy vs Methotrexate Monotherapy for Maintenance of Rheumatoid Arthritis Remission

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT02373813
First received: January 12, 2015
Last updated: March 21, 2017
Last verified: March 2017
  Purpose

The purpose of this study is to evaluate the efficacy of etanercept monotherapy compared to methotrexate monotherapy on maintenance of remission in subjects with Rheumatoid Arthritis who were on etanercept plus methotrexate therapy.

This is a multicenter, randomized withdrawal, double-blind controlled study in subjects with Rheumatoid Arthritis on etanercept plus methotrexate therapy who are in very good disease control for 6 months prior to study entry. The study will consist of a 30-day screening period, a 24-week open label run-in period, a 48-week double-blind treatment period and a 30-day safety follow-up period.

Approximately 465 subjects will be enrolled and approximately 325 subjects will be randomly assigned in a 2:2:1 ratio to one of three treatment groups: etanercept 50 mg weekly by subcutaneous injection plus oral placebo for methotrexate (n = 130), oral methotrexate 10 to 25 mg weekly plus placebo for etanercept (n = 130) and etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly (n = 65).


Condition Intervention Phase
Rheumatoid Arthritis
Drug: etanercept pre-filled syringe sq injection
Drug: Oral methotrexate
Drug: Placebo for etanercept sq injection
Drug: Placebo for methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Randomized Withdrawal Double-blind Study of Etanercept Monotherapy Compared to Methotrexate Monotherapy for Maintenance of Remission in Subjects With Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Simplified Disease Activity Index (SDAI) remission (≤ 3.3) at week 48 [ Time Frame: Week 48 Visit ]

Secondary Outcome Measures:
  • SDAI score and change from baseline at all measured timepoints [ Time Frame: Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • Disease activity score (28 joint) calculated using the erythrocyte sedimentation rate formula (DAS-28-ESR) and change from baseline at all measured timepoints [ Time Frame: Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • Disease activity score (28 joint) using the C-reactive protein formula (DAS-28-CRP) and change from baseline at all measured timepoints [ Time Frame: Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • Clinical Disease Activity Index (CDAI) and change from baseline at all measured timepoints [ Time Frame: Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • Disease worsening defined as an SDAI > 3.3 and ≤ 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and ≤ 11 on three or more separate visits or SDAI > 11 after randomization. [ Time Frame: Visit at 24 weeks prior to Day 1, Visit at 12 weeks prior to Day 1, Visit at 1 week prior to Day1, Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • Time to disease worsening defined as an SDAI > 3.3 and ≤ 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and ≤ 11 on three or more separate visits or SDAI > 11 after randomization. [ Time Frame: Visit at 24 weeks prior to Day 1, Visit at 12 weeks prior to Day 1, Visit at 1 week prior to Day1, Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • In subjects that receive rescue treatment:Time to recapture SDAI remission after starting rescue treatment and SDAI remission at week 48 [ Time Frame: Timepoints dependent on when rescue is started, but could include Visit at 24 weeks prior to Day 1, Visit at 12 weeks prior to Day 1, Visit at 1 week prior to Day1, Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • SDAI remission (≤ 3.3) at all measured timepoints [ Time Frame: Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • Boolean remission (at a single time point a subject must satisfy all of the following: tender joint count, swollen joint count, c-reactive protein and patient global assessment must each be less than or equal to 1) at all measured timepoints. [ Time Frame: Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]
  • Time to recapture SDAI remission after starting rescue treatment [ Time Frame: Between rescue and remission or Week 48, whichever comes first. ]
    In subjects that receive rescue treatment during the double-blind treatment period, measure the time to recapture SDAI remission after starting rescue treatment.

  • SDAI remission at week 48 for subjects that receive rescue treatment. [ Time Frame: Week 48 ]
    In subjects that receive rescue treatment during the double-blind treatment period, measure SDAI remission at week 48


Other Outcome Measures:
  • Safety of etanercept and methotrexate by assessing the adverse events, serious adverse events and lab parameters of participants in the study. [ Time Frame: Visit at 24 weeks prior to Day 1, Visit at 12 weeks prior to Day 1, Visit at 1 week prior to Day1, Day 1, Week 12, Week 24, Week 36 and Week 48 visits ]

Estimated Enrollment: 465
Actual Study Start Date: February 20, 2015
Estimated Study Completion Date: May 18, 2020
Estimated Primary Completion Date: May 18, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: etanercept monotherapy
etanercept for injection in pre-filled syringes with placebo for methotrexate
Drug: etanercept pre-filled syringe sq injection
etanercept for injection in pre-filled syringes
Drug: Placebo for methotrexate
methotrexate placebo capsules
Experimental: methotrexate monotherapy
Oral methotrexate with placebo for etanercept
Drug: Oral methotrexate
methotrexate capsules
Drug: Placebo for etanercept sq injection
etanercept placebo for injection in pre-filled syringes
Experimental: etanercept plus methotrexate
etanercept for injection in pre-filled syringes and oral Methotrexate
Drug: etanercept pre-filled syringe sq injection
etanercept for injection in pre-filled syringes
Drug: Oral methotrexate
methotrexate capsules

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be adults with a history of moderate to severe Rheumatoid Arthritis;
  • Subjects must be in very good Rheumatoid Arthritis disease control for ≥ 6 months and be in remission as defined by a Simplified Disease Activity Index ≤ 3.3 at screening and at the end of the run-in period.
  • Subjects must be on etanercept 50 mg per week plus methotrexate therapy for ≥ 6 months prior to the start of the run-in period. The methotrexate dose must be 10 to 25 mg per week for ≥ 6 months prior to the start of the run-in period and the dose must be stable for ≥ 8 weeks prior to the start of the run-in period.
  • Subject has no known history of active tuberculosis, and has a negative test for tuberculosis during screening.

Exclusion Criteria:- Subject has used biologic disease modifying antirheumatic drug other than etanercept OR has used an oral janus kinase inhibitor ≤ 6 months prior to run-in visit 1

  • Subject has any active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to run-in visit 1.
  • Subject has known alcohol addiction or dependency or uses alcohol daily.
  • Subject has one or more significant concurrent medical conditions per investigator judgment, including the following:

    • poorly controlled diabetes
    • chronic kidney disease stage IIIb, IV, or V
    • symptomatic heart failure (New York Heart Association class II, III, or IV)
    • myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization
    • uncontrolled hypertension
    • severe chronic pulmonary disease (eg, requiring oxygen therapy)
    • multiple sclerosis or any other demyelinating disease
    • major chronic inflammatory disease or connective tissue disease other than Rheumatoid Arthritis (eg, systemic lupus erythematosus with the exception of secondary Sjögren's syndrome)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02373813

Contacts
Contact: Amgen Call Center 866-572-6436

  Show 118 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02373813     History of Changes
Other Study ID Numbers: 20110186
Study First Received: January 12, 2015
Last Updated: March 21, 2017

Additional relevant MeSH terms:
Etanercept
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on March 24, 2017