A study comparing the use of etanercept and methotrexate, used either alone or in combination, for maintaining remission in rheumatoid arthritis.

• Register: EUCTR
• Last refreshed on: 25 August 2020
• Main ID: EUCTR2014-004868-38-BG
• Date of registration: 22/12/2015
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc.
• Public title: A study comparing the use of etanercept and methotrexate, used either alone or in combination, for maintaining remission in rheumatoid arthritis.
• Scientific title: A Randomized Withdrawal Double-blind Study of Etanercept Monotherapy Compared to Methotrexate Monotherapy for Maintenance of Remission in Subjects With Rheumatoid Arthritis.
• Date of first enrolment: 02/02/2016
• Target sample size: 358
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004868-38
• 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: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, United States

Contacts

• Name: Medical Information
• Affiliation: Amgen (EUROPE) GmbH

• Name: Medical Information
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
In very good RA disease control for = 6 months in the opinion of the investigator
Receiving treatment with etanercept for RA for = 6 months prior to run-in visit 1
Receiving treatment with methotrexate of 10 mg to 25 mg weekly for = 6 months AND on a stable dose of oral methotrexate for = 8 weeks prior to run-in visit 1
= 18 years of age at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 108

Exclusion criteria:
Subject has known history of alcoholic hepatitis, nonalcoholic steatohepatitis or immunodeficiency syndromes, including Human Immunodeficiency Virus infection.
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 a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to run-in visit 1.
Subject has used biologic DMARD other than etanercept OR has used an oral janus kinase inhibitor = 6 months 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



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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 20.0 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
Product Name: Enbrel
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Methotrexate
Product Name: methotrexate
Pharmaceutical Form: Tablet
INN or Proposed INN: methotrexate
CAS Number: 59-05-2
Current Sponsor code: methotrexate
Other descriptive name: METHOTREXATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 48

Primary end point(s): Simplified Disease Activity Index (SDAI) remission (= 3.3)

Main Objective: 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 combination therapy.

Secondary Objective: To evaluate the efficacy of etanercept plus methotrexate therapy compared to methotrexate monotherapy on maintenance of remission.
To evaluate the efficacy of 1) etanercept monotherapy compared to methotrexate monotherapy and 2) etanercept plus methotrexate therapy compared to methotrexate monotherapy on:
- disease activity
- disease worsening and time to disease worsening
- remission and time to recapture remission after rescue treatment

Secondary Outcome(s)

Secondary end point(s): 1. SDAI score and change from baseline at all measured timepoints
2. Disease activity score (28 joint) calculated using the erythrocyte sedimentation rate formula (DAS-28-ESR) and change from baseline at all measured timepoints
3. Disease activity score (28 joint) using the C-reactive protein formula (DAS-28-CRP) and change from baseline at all measured timepoints
4. Clinical Disease Activity Index (CDAI) and change from baseline at all measured timepoints
5. SDAI remission (= 3.3) at all measured timepoints
6. Boolean remission at all measured timepoints
7. 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
8. 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
9. In subjects that receive rescue treatment:
• Time to recapture SDAI remission after starting rescue treatment
• SDAI remission at week 48

Timepoint(s) of evaluation of this end point: All subjects:
•SDAI score, Disease activity score [DAS-28-ESR and DAS-28-CRP], Clinical Disease Activity Index, SDAI remission and Boolean remission evaluated Day 1, week 12, 24, 36 and 48 weeks.
•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 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.

In subjects that receive rescue treatment during the double-blind treatment period:
•Time to recapture SDAI remission after starting rescue treatment
•SDAI remission at week 48

Secondary ID(s)

2014-004868-38-GR

20110186

Source(s) of Monetary Support

Amgen Inc

Ethics review

Status: Approved
Approval date: 02/02/2016
Contact: