Prospective Study on Intensive Early Rheumatoid Arthritis Treatment

NCT ID: NCT00480272

Last Updated: 2017-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 251 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2017-03-01

Brief Summary

Hypothesis: Early intensive treatment with anti-TNF agent plus methotrexate plus high dose prednisone may increase remission rate and may induce stable remission in Rheumatoid Arthritis Objective: to evaluate induction of remission using adalimumab, prednisone and methotrexate and maintenance of remission after discontinuation of adalimumab and prednisone

Detailed Description

Treatment group A 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + prednisone 50 mg/d tapered to 6.25 mg 6 - 12 months: Adalimumab 40 mg eow plus methotrexate 20 mg weekly group B 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + placebo 6 - 12 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly

Follow up period - Open Label phase:

Patients achieving clinical remission will be than treated only with MTX and observed for another 12 months period. Patients who do not achieve clinical remission or patients who will experience a relapse of the disease will be treated according to standard of care (SOC) modalities.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

group A

• adalimumab 40 mg subcutaneous injections every other week from baseline to month 12
• methotrexate orally weekly at initial dose of 10 mg rising to 20 mg weekly over 4 weeks in 2.5 mg increments, continued up to month 24.
• prednisone orally 50 mg daily, gradually tapered up to 6.25 mg at week 7 and stopped at month 6

Group Type: EXPERIMENTAL

adalimumab, plus prednisone

Intervention Type: DRUG

adalimumab 40 mg/sc every 2 weeks plus methotrexate 20 mg/po every week plus placebo or prednisone 50 mg/po day then reduced to 6.25/po day

group B

• adalimumab 40 mg subcutaneous injections every other week from baseline to the end of month 12
• methotrexate orally oweekly at an initial dose of 10 mg rising to 20 mg weekly over 4 weeks in 2.5 mg increments, continued up to month 24.
• placebo orally, stopped at month 6

Group Type: PLACEBO_COMPARATOR

adalimumab plus placebo

Intervention Type: DRUG

adalimumab 40 mg/sc every 2 weeks plus methotrexate 20 mg/po every week plus placebo daily for 6 months

Interventions

adalimumab, plus prednisone

adalimumab 40 mg/sc every 2 weeks plus methotrexate 20 mg/po every week plus placebo or prednisone 50 mg/po day then reduced to 6.25/po day

Intervention Type: DRUG

adalimumab plus placebo

adalimumab 40 mg/sc every 2 weeks plus methotrexate 20 mg/po every week plus placebo daily for 6 months

Intervention Type: DRUG

Other Intervention Names

humira (adalimumab); deltacortene (prednisone); humira (adalimumab)

Eligibility Criteria

Inclusion Criteria

• Active rheumatoid arthritis diagnosed for at least 6 weeks, but no more than 1 year, according to the revised 1987 ACR criteria
• Naïve to treatment with MTX
• Swollen joint count (SJC) > 8 tender joint count (TJC) > 8
• At screening CRP > 1.5 mg/dL (15 mg/L) or ESR ≥ 28 mm/h
• ≥ 1 joint erosion or RF positivity or anti-CCP positivity
• Age 18-70 years.

Exclusion Criteria

• Rheumatic autoimmune disease other than RA
• Functional class IV
• Any surgical procedure within 12 weeks prior to baseline or planned during the study.
• Pregnancy or breast feeding.
• Evidence of significant concomitant disease
• Primary or secondary immunodeficiency
• active infection of any kind
• History of previously untreated infection with mycobacterium tuberculosis or current treatment for same.
• History of cancer
• Any history or presence of congestive heart failure (CHF) (New York Heart Association classification for CHF: Class III or IV).
• Any history of myocardial infarction within 5 years.
• History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of adalimumab or methotrexate.
• Positive serology for hepatitis B or C indicating active infection.
• Hemoglobin < 8.0 g/dL.
• Absolute neutrophil count (ANC) < 1.5 x 103/L.
• Liver function abnormality

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Carlomaurizio Montecucco

Director, Academic Division of Rheumatology, IRCCS Policlinico S. Matteo and University of Pavia

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

carlomaurizio montecucco, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS S. Matteo Foundation, Pavia

Locations

IRCCS S. Matteo Hospital

Pavia, Pavia, Italy

Countries

Italy

Other Identifiers

2006-003843-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CURE

Identifier Type: -

Identifier Source: org_study_id