Clinical trial NCT01232569: A Study of RoActemra/Actemra (Tocilizumab) Given Subcutaneously in Combination With Traditional DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis
Official title: A Randomized, Double-blind, Parallel Group Study of Safety and the Effect on Clinical Outcome of Tocilizumab Subcutaneous (sc) Versus Placebo sc in Combination With Traditional Disease Modifying Anti-rheumatic Drugs (DMARDs) in Patients With Moderate to Severe Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-11-02
Enrollment: 656
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 randomized, parallel-group, placebo-controlled, multicenter study will evaluate the reduction in disease activity and the safety of tocilizumab (RoActemra/Actemra) in combination with traditional disease-modifying anti-rheumatic drugs (DMARDs) in patients with active, moderate to severe rheumatoid arthritis. In the double-blind part of the study, patients will be randomized to receive either 162 mg tocilizumab or placebo subcutaneously every 2 weeks for 24 weeks using a pre-filled syringe. In the open-label part of the study, patients will be randomized to receive 162 mg tocilizumab subcutaneously every 2 weeks from Week 24 to Week 96 using a pre-filled syringe or an auto-injector.


Eligibility criteria: Inclusion Criteria:

* Adult patients, ≥ years of age.
* Moderate to severe rheumatoid arthritis of ≥ 6 months duration.
* Receiving treatment on an outpatient basis.
* Swollen joint count (SJC) ≥ 6 (66 joint count) and tender joint count (TJC)≥ 8 (68 joint count) at screening and study start.
* On a stable dose of disease-modifying anti-rheumatic drugs for at least 8 weeks prior to study start.

Exclusion Criteria:

* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
* Rheumatic autoimmune disease other than rheumatoid arthritis, Secondary Sjögren's Syndrome with rheumatoid arthritis is allowed.
* Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.
* Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16 years.
* Prior history of or current inflammatory joint disease other than rheumatoid arthritis.
* History of malignancy, active or recurrent infections, positive to hepatitis B surface antigen or hepatitis C antibody, active tuberculosis, serious allergy to biologics, or a history of diverticular disease or other symptomatic GI conditions that might predispose to perforations.

Other inclusion and exclusion criteria applied to the study.

Primary outcomes:
measure: Percentage of Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Percentage of Patients With ACR50 and ACR70 Responses at Week 24
timeFrame: Baseline to Week 24
measure: Time to Onset of ACR20, ACR50, and ACR70 Responses
timeFrame: Baseline to Week 24
measure: Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in C-reactive Protein at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Erythrocyte Sedimentation Rate at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score
timeFrame: Baseline to Week 24
measure: Change From Baseline in the Patient's Pain Visual Analog Score
timeFrame: Baseline to Week 24
measure: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Patients With an Improvement of ≥ 0.3 Units From Baseline in the HAQ-DI Score at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Disease Activity Score 28 (DAS28) at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Patients With a DAS28 Score ≤ 3.2 (DAS28 Low Disease Activity) at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Patients With a DAS28 Score < 2.6 (DAS28 Remission) at Week 24
timeFrame: Week 24
measure: Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in the Van Der Heijde Modified Sharp Radiographic Score at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Hemoglobin at Week 24
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Peoria
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Fullerton
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Leandro
country: United States
state: California
city: West Hills
country: United States
state: California
city: Trumbull
country: United States
state: Connecticut
city: Boca Raton
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Ormond Beach
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Gainesville
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Meridan
country: United States
state: Idaho
city: Springfield
country: United States
state: Illinois
city: Vernon Hills
country: United States
state: Illinois
city: Crofton
country: United States
state: Maryland
city: Hagerstown
country: United States
state: Maryland
city: Wheaton
country: United States
state: Maryland
city: Flowood
country: United States
state: Mississippi
city: Jackson
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: St Louis
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Brooklyn
country: United States
state: New York
city: Belmont
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Allentown
country: United States
state: Pennsylvania
city: Bethlehem
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Wexford
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Memphis
country: United States
state: Tennessee
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: San Antonio
country: United States
state: Texas
city: Tacoma
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Córdoba
country: Argentina
city: San Miguel de Tucuman
country: Argentina
city: Cairns
country: Australia
city: Kogarah
country: Australia
city: Curitiba
country: Brazil
city: Goiania
country: Brazil
city: Juiz de Fora
country: Brazil
city: Porto Alegre
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: Sao Paulo
country: Brazil
city: Sao Paulo
country: Brazil
city: São Paulo
country: Brazil
city: São Paulo
country: Brazil
city: Vitoria
country: Brazil
city: Plovdiv
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Winnipeg
country: Canada
state: Manitoba
city: Winnipeg
country: Canada
state: Manitoba
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Pointe-claire
country: Canada
state: Quebec
city: Bogota
country: Colombia
city: Chia-cundinamarca
country: Colombia
city: Medellin
country: Colombia
city: Athens
country: Greece
city: Athens
country: Greece
city: Thessaloniki
country: Greece
city: Guatemala City
country: Guatemala
city: Guatemala City
country: Guatemala
city: Guatemala City
country: Guatemala
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Ashkelon
country: Israel
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Ramat Gan
country: Israel
city: Rishon Lezion
country: Israel
city: Tel Aviv
country: Israel
city: Batu Caves
country: Malaysia
city: Kota Kinabalu
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Chihuahua
country: Mexico
city: Culiacan
country: Mexico
city: Guadalajara
country: Mexico
city: Leon
country: Mexico
city: Merida
country: Mexico
city: Mexicali
country: Mexico
city: Mexico
country: Mexico
city: Morelia
country: Mexico
city: Obregon
country: Mexico
city: Queretaro
country: Mexico
city: Queretaro
country: Mexico
city: Otahuhu
country: New Zealand
city: Panama City
country: Panama
city: Cebu
country: Philippines
city: Davao
country: Philippines
city: Manila
country: Philippines
city: Bytom
country: Poland
city: Dzialdowo
country: Poland
city: Elblag
country: Poland
city: Koscian
country: Poland
city: Krakow
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint-petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: UFA
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Durban
country: South Africa
city: Pinelands
country: South Africa
city: Pretoria
country: South Africa
city: La Coruna
country: Spain
city: Oviedo
country: Spain
city: Sevilla
country: Spain
city: Fribourg
country: Switzerland
city: Genève
country: Switzerland
city: Lausanne
country: Switzerland
city: Zürich
country: Switzerland
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kivitz A, Olech E, Borofsky M, Zazueta BM, Navarro-Sarabia F, Radominski SC, Merrill JT, Rowell L, Nasmyth-Miller C, Bao M, Wright S, Pope JE. Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2014 Nov;66(11):1653-61. doi: 10.1002/acr.22384.