Clinical trial NCT00891020: A Study Of Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have an Inadequate Response to or Are Unable to Tolerate Biologic and Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs)
Official title: Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs and Monotherapy Who Have an Inadequate Response to Current Non-Biologic or Biologic DMARDs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-04-30
Enrollment: 886
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 3 arm randomized open label study will evaluate the safety, tolerability and efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis, who have had inadequate response to or are unable to tolerate DMARDs. The protocol incorporates risk mitigation strategies developed in partnership with the FDA to manage known and potential risks associated with the treatment of tocilizumab. Patients will be randomized to receive tocilizumab either 4 mg/kg intravenous (iv) or 8 mg/kg iv with concomitant non-biologic DMARDs, or 8 mg/kg iv without concomitant non-biologic DMARDs, every 4 weeks, for a total of 6 infusions. The anticipated time on study treatment is 3-12 months, and the target sample size is 500-1000 individuals.


Eligibility criteria: Inclusion Criteria:

* adult patients, \>=18 years of age;
* moderate to severe active rheumatoid arthritis for \>6 months;
* inadequate clinical response or unable to tolerate current or prior biologic or non-biologic Disease-modifying antirheumatic drug (DMARD) therapy;
* Swollen joint count (SJC) \>/=4 and Tender joint count (TJC) \>/=4
* body weight \</=150kg
* current permitted non-biologic DMARDs must be on stable dose for \>/= 7 weeks prior to baseline;

Exclusion Criteria:

* history of autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
* functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in rheumatoid arthritis;
* treatment with rituximab within 6 months before screening;
* intraarticular corticosteroids within 8 weeks or intramuscular (im)/ intravenous (iv) corticosteroids within 12 weeks prior to screening;
* known active current or history of recurrent infections, or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening.

Primary outcomes:
measure: Percentage of Participants Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period
timeFrame: 24 Weeks
Secondary outcomes:
measure: Percentage of Participants Experiencing Serious Adverse Events of Special Interest
timeFrame: 24 Weeks
measure: Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest
timeFrame: 24 Weeks
measure: Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24
timeFrame: Weeks 8,16,24
measure: Change From Baseline in DAS28 Score at Weeks 8, 16 and 24
timeFrame: Baseline, Weeks 8,16,24
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8,16,24
measure: Percentage of Participants With Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Week 8
timeFrame: Baseline, Week 8
measure: Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20
timeFrame: Weeks 12,16, 20
measure: Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8,16,24
measure: Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8,16,24
Other outcomes:
Locations:
city: Anniston
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Montgomery
country: United States
state: Alabama
city: Tuscaloosa
country: United States
state: Alabama
city: Hot Springs
country: United States
state: Arizona
city: Paradise Valley
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Fayetteville
country: United States
state: Arkansas
city: Fort Smith
country: United States
state: Arkansas
city: Jonesboro
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state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Covina
country: United States
state: California
city: Escondido
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Huntington Beach
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Lakewood
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Murrieta
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Leandro
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Sherman Oaks
country: United States
state: California
city: Van Nuys
country: United States
state: California
city: Victorville
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state: California
city: Westlake Village
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state: California
city: Whittier
country: United States
state: California
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state: Colorado
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city: Fall River
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city: Lansing
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city: St Clair Shores
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city: Eagan
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city: Edina
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city: Hattiesburg
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city: Tupelo
country: United States
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city: Florissant
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city: Lebanon
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city: Haddon Heights
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city: Manalapan
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city: Hewlett
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city: Lake Success
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city: Olean
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city: Orchard Park
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city: Plainview
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city: Rochester
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city: Belmont
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city: Durham
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city: Middleburg Heights
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city: Oklahoma City
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city: Tulsa
country: United States
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city: Lake Oswego
country: United States
state: Oregon
city: Bethlehem
country: United States
state: Pennsylvania
city: Camp Hill
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Lebanon
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pottstown
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Wexford
country: United States
state: Pennsylvania
city: Willow Grove
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Hickory
country: United States
state: South Carolina
city: Myrtle Beach
country: United States
state: South Carolina
city: Hendersonville
country: United States
state: Tennessee
city: Hixson
country: United States
state: Tennessee
city: Jackson
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Amarillo
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Carrollton
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: Mesquite
country: United States
state: Texas
city: Nassau Bay
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Burlington
country: United States
state: Vermont
city: Arlington
country: United States
state: Virginia
city: Burke
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Olympia
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Beckley
country: United States
state: West Virginia
city: Clarksburg
country: United States
state: West Virginia
city: Brookfield
country: United States
state: Wisconsin
city: Franklin
country: United States
state: Wisconsin
city: Glendale
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Onalaska
country: United States
state: Wisconsin
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Weinblatt ME, Kremer J, Cush J, Rigby W, Teng LL, Devenport J, Singh N, Lepley D, Genovese MC. Tocilizumab as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs: twenty-four-week results of an open-label, clinical practice study. Arthritis Care Res (Hoboken). 2013 Mar;65(3):362-71. doi: 10.1002/acr.21847.