Clinical trial NCT01962974: A Golimumab Phase 3b, Multicenter, Assessment of Intravenous Efficacy in Rheumatoid Arthritis Subjects Who Have Diminished Disease Control Despite Treatment With Infliximab (REMICADE®)
Official title: A Golimumab Phase 3b, Multicenter, Assessment of Intravenous Efficacy in Rheumatoid Arthritis Subjects Who Have Diminished Disease Control Despite Treatment With Infliximab (REMICADE®)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid
Lead sponsor: Janssen Biotech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-10-16
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 3b, multicenter study of the efficacy of golimumab 2 mg/kg IV in subjects with active rheumatoid arthritis who are receiving methotrexate and have inadequate disease control (defined as an erythrocyte sedimentation rate \[ESR\]-based Disease Activity Score in 28 joints \[DAS28\] ≥ 3.2 and ≥ 4 swollen and ≥ 4 tender joints) despite current anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks.

To be eligible for participation, subjects must have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, who have since exhibited a diminished response despite continued treatment. It is estimated that 200 subjects will be enrolled in the study at approximately 85 global sites.

Detailed description: The study employs an open-label "active switch" design that moves subjects from infliximab to golimumab 2 mg/kg IV. In general, subjects eligible for the study include men or women who are currently receiving infliximab in actual clinical practice who are at least 18 years of age with active rheumatoid arthritis, and have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, but now exhibit a diminished response and inadequate disease control despite continued treatment. Subjects must have received infliximab in combination with methotrexate for a minimum of 9 months prior to the first screening visit.

The screening visit will occur sometime between Week -12 and Week -10. Consenting subjects who meet screening criteria will receive their final dose of infliximab at Week -8 as part of actual clinical practice. Golimumab IV treatment, which will be supplied by the sponsor, will be received at Weeks 0, 4, 12, 20, and 28. The primary endpoint is at Week 24, the final efficacy assessment is at Week 32, and a follow-up safety assessment by telephone is at Week 44. There will be a maximum of 36 weeks between the last infliximab infusion at Week -8 and the last infusion of golimumab at Week 28. The duration of study participation is expected to be a maximum of 56 weeks (including the Screening Period, 32 weeks of golimumab treatment and assessment, and a 12-week safety follow-up).

Eligibility criteria: Major Inclusion Criteria include (but not limited to):

* Have a diagnosis of Rheumatoid Arthritis (according to the revised 1987 criteria of the American Rheumatism Association).
* Treatment with infliximab and methotrexate for \>= 9 months, (with stable doses of methotrexate over last 16 weeks of 7.5 mg/week to 25 mg/week) and (anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks).
* Disease Activity Score 28 (DAS28) ≥ 3.2 based on Erythrocyte Sedimentation Rate (ESR) at Week -8 and Week 0.
* Swollen joint count (SJC) ≥ 4 and tender joint count (TJC) ≥ 4 at Week - 8 and at Week 0.
* Prior response confirmed by physician.

Major Exclusion Criteria include (but not limited to):

* Have a history of latent or active granulomatous infection, including histoplasmosis, or Have a history of latent or active granulomatous infection, including histoplasmosis, or coccidioidomycosis, prior to the first screening visit or during the Screening Period.
* Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
* Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis.
* Have previously received more than 1 of the currently approved subcutaneous (SC) administered anti-TNFα agents, etanercept, certolizumab pegol, golimumab, or adalimumab.
* Are pregnant, nursing, or planning a pregnancy or fathering a child within 6 months after receiving the last administration of the study agent.
* Weight less than 35 kg or greater than 110 kg (less than 77 pounds or greater than 242 pounds).

Primary outcomes:
measure: Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Who Achieved an ACR 20 Response at Week 24 With Confirmed Presence of Antibodies to Infliximab
timeFrame: Week 24
measure: Percentage of Participants Who Acheived ACR 20 Response at Week 24 With Trough Infliximab Levels Below the Lower Limit of Quantification (LLOQ)
timeFrame: Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Fort Smith
country: United States
state: Arkansas
city: Fremont
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Thousand Oaks
country: United States
state: California
city: Whittier
country: United States
state: California
city: Bridgeport
country: United States
state: Connecticut
city: Clearwater
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Coeur D'Alene
country: United States
state: Idaho
city: Indianapolis
country: United States
state: Indiana
city: South Bend
country: United States
state: Indiana
city: Eagan
country: United States
state: Minnesota
city: Edina
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Albuquerque
country: United States
state: New Mexico
city: Orchard Park
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Dayton
country: United States
state: Ohio
city: Duncansville
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Myrtle Beach
country: United States
state: South Carolina
city: Hixson
country: United States
state: Tennessee
city: Jakson
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Arlington
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Glendale
country: United States
state: Wisconsin
city: Victoria
country: Canada
state: British Columbia
city: Saint-John'S
country: Canada
state: Newfoundland and Labrador
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: Hamilton
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Rimouski
country: Canada
Study officials:
References: