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

Amgen

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo for etanercept subcutaneous injection; Drug: Placebo for methotrexate; Dietary Supplement: Folic acid (non-investigational product); Drug: Oral methotrexate; Drug: etanercept pre-filled syringe subcutaneous injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT02373813

20110186

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy of etanercept monotherapy compared to methotrexate monotherapy on maintenance of remission in participants with rheumatoid arthritis (RA) who were on etanercept plus methotrexate therapy.

This is a multicenter, randomized withdrawal, double-blind controlled study in participants 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.

Enrollment: 371 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (Part 1, Run-In Period):

• 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 (Part 1, Run-In Period):

• 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)

Inclusion Criteria (Part 2, Treatment Period):

• SDAI ≤ 3.3 at run-in visit 3
• Subject if female and not at least 2 years postmenopausal or history of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, has a negative urine pregnancy test at baseline (day 1).

Exclusion Criteria (Part 2, Treatment Period):

• Any clinically significant change in the Part 1 eligibility criteria during the run-in period
• SDAI > 3.3 and ≤ 11 on two consecutive visits at least two weeks apart OR SDAI > 3.3 and ≤ 11 on two or more separate visits OR SDAI > 11 at any time during the run-in period
• Subject has a clinically significant laboratory abnormality during run-in period which in the opinion of the investigator poses a safety risk, will prevent the subject from completing the study, or will interfere with the interpretation of the study results during the run-in period.

NOTE: Other inclusion/exclusion criteria may apply per protocol.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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371 participants in 4 patient groups

Open Label Run-In: Etanercept plus Methotrexate

Experimental group

Description:

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 24 weeks. Participants also receive folic acid as standard of care.

Treatment:

Drug: etanercept pre-filled syringe subcutaneous injection

Dietary Supplement: Folic acid (non-investigational product)

Drug: Oral methotrexate

Double-Blind Treatment: Methotrexate Monotherapy

Experimental group

Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will initiate rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Treatment:

Drug: etanercept pre-filled syringe subcutaneous injection

Dietary Supplement: Folic acid (non-investigational product)

Drug: Oral methotrexate

Drug: Placebo for etanercept subcutaneous injection

Double-Blind Treatment: Etanercept Monotherapy

Experimental group

Description:

Etanercept 50 mg weekly by subcutaneous injection plus placebo for methotrexate for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will initiate rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Treatment:

Drug: etanercept pre-filled syringe subcutaneous injection

Dietary Supplement: Folic acid (non-investigational product)

Drug: Oral methotrexate

Drug: Placebo for methotrexate

Double-Blind Treatment: Etanercept plus Methotrexate

Experimental group

Description:

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will continue on the assigned treatments (as rescue treatment).

Treatment:

Drug: etanercept pre-filled syringe subcutaneous injection

Dietary Supplement: Folic acid (non-investigational product)

Drug: Oral methotrexate