Clinical trial NCT01194414: A Study to Compare Subcutaneous Versus Intravenous Administration of RoActemra/Actemra (Tocilizumab) in Participants With Moderate to Severe Active Rheumatoid Arthritis
Official title: A Randomized, Double-blind, Parallel Group Study of the Safety and Effect on Clinical Outcome of Tocilizumab SC Versus Tocilizumab IV, 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: 2010-09-03
Enrollment: 1262
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, double-blind, parallel group study compares the efficacy and safety of subcutaneous (sc) versus intravenous (iv) administration of tocilizumab in participants with moderate to severe active rheumatoid arthritis. Participants were randomized to receive either tocilizumab 162 mg sc weekly plus iv placebo every 4 weeks, or tocilizumab 8 mg/kg iv every 4 weeks plus sc placebo weekly during the double-blind period from baseline to Week 24. The double-blind period was followed by a 72-week open-label treatment with some switching of sc and iv administration. No placebo was administered in the open-label phase. Participants continued on their stable dose of disease-modifying antirheumatic drugs (DMARDs) throughout the study. Anticipated time on study treatment was 2 years.


Eligibility criteria: Inclusion Criteria:

* Adult participants, ≥ 18 years of age
* Rheumatoid arthritis of ≥ 6 months duration, according to American College of Rheumatology (ACR) criteria
* Swollen joint count (SJC) ≥ 4 (66 joint count), tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline
* Inadequate response to current DMARD therapy
* Permitted DMARDs must be at stable dose for ≥ 8 weeks prior to baseline
* Oral corticosteroids (≤ 10 mg/day prednisone or equivalent) and NSAIDs (up to maximum recommended dose) must be at stable dose for ≥ 4 weeks prior to baseline

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 RA
* Functional class IV (ACR classification)
* Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before the age of 16
* Prior history of or current inflammatory joint disease other than RA
* Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
* Previous treatment with tocilizumab
* Active current or history of recurrent infection

Primary outcomes:
measure: Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR20) Response at Week 24
timeFrame: Baseline, 24 weeks
measure: Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments
timeFrame: Baseline to up to 3 months after last dose of study drug (approximately up to 2 years)
Secondary outcomes:
measure: Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR50) Response at Week 24
timeFrame: Baseline, 24 weeks
measure: Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR70) Response at Week 24
timeFrame: Baseline, 24 weeks
measure: Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 24
timeFrame: Week 24
measure: Percentage of Participants Achieving a Decrease of ≥ 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24
timeFrame: Baseline, 24 Weeks
measure: Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 24
timeFrame: 24 Weeks
measure: Percentage of Participants With American College of Rheumatology Criteria (ACR20, ACR50, ACR70) at Week 97
timeFrame: Week 97
measure: Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 97
timeFrame: Week 97
measure: Percentage of Participants Achieving a Decrease of ≥0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 97
timeFrame: Baseline, Week 97
measure: Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 97
timeFrame: Week 97
measure: Area Under the Serum Concentration Curve of Tocilizumab After First SC Injection or IV Infusion
timeFrame: Week 0: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after first dose
measure: Area Under the Serum Concentration Curve of Tocilizumab at Steady State for SC and IV Treatment
timeFrame: Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose.
measure: Minimum Serum Concentration (Cmin) of Tocilizumab
timeFrame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose
measure: Maximum Serum Concentration (Cmax) of Tocilizumab
timeFrame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose
measure: Time to Maximum Serum Concentration (Tmax) of Tocilizumab
timeFrame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose
measure: Change From Baseline in Serum Interleukin-6 (IL-6) Concentration at Week 25
timeFrame: Baseline, Week 25
measure: Change From Baseline in Serum Soluble Interleukin-6 Receptor (sIL-6R) Concentration at Week 97
timeFrame: Baseline, Week 97
measure: Percentage of Participants Who Developed Antibodies To Tocilizumab at Week 97
timeFrame: Week 97
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Tuscaloosa
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Upland
country: United States
state: California
city: Van Nuys
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Bridgeport
country: United States
state: Connecticut
city: Delray Beach
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: South Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Coeur D'alene
country: United States
state: Idaho
city: Morton Grove
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Monroe
country: United States
state: Louisiana
city: Petoskey
country: United States
state: Michigan
city: St. Claire Shores
country: United States
state: Michigan
city: Eagan
country: United States
state: Minnesota
city: Florissant
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Lebanon
country: United States
state: New Hampshire
city: Clifton
country: United States
state: New Jersey
city: Manalapan
country: United States
state: New Jersey
city: Voorhees
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Albany
country: United States
state: New York
city: Binghamton
country: United States
state: New York
city: Orchard Park
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Raleigh
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state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Cincinnati
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state: Ohio
city: Toledo
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city: Oklahoma City
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country: United States
state: Pennsylvania
city: Charleston
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state: South Carolina
city: Charleston
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state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Memphis
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city: Houston
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state: Texas
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state: Washington
city: Seattle
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country: United States
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country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
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country: Argentina
city: Rosario
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city: Adelaide
country: Australia
city: Adelaide
country: Australia
city: Clayton
country: Australia
city: Geelong
country: Australia
city: Hobart
country: Australia
city: Malvern East
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city: Maroochydore
country: Australia
city: New Lambton
country: Australia
city: Curitiba
country: Brazil
city: Goiania
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city: Juiz de Fora
country: Brazil
city: Porto Alegre
country: Brazil
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
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country: Brazil
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city: Sofia
country: Bulgaria
city: Sofia
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city: Sofia
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city: Edmonton
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state: Alberta
city: Kelowna
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state: British Columbia
city: Vancouver
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state: British Columbia
city: St 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: Hamilton
country: Canada
state: Ontario
city: Kitchener
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: St. Catharines
country: Canada
state: Ontario
city: Windsor
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec City
country: Canada
state: Quebec
city: Rimouski
country: Canada
state: Quebec
city: Sainte-foy
country: Canada
state: Quebec
city: Trois-rivieres
country: Canada
state: Quebec
city: Saskatoon
country: Canada
state: Saskatchewan
city: Barranquilla
country: Colombia
city: Bogota
country: Colombia
city: Bogotá
country: Colombia
city: Bordeaux
country: France
city: Le Mans
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Paris
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
city: Bad Bramstedt
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Essen
country: Germany
city: Freiburg
country: Germany
city: Gommern
country: Germany
city: Heidelberg
country: Germany
city: Herne
country: Germany
city: Hildesheim
country: Germany
city: Köln
country: Germany
city: Ludwigshafen
country: Germany
city: Osnabrück
country: Germany
city: Ratingen
country: Germany
city: Rostock
country: Germany
city: Würzburg
country: Germany
city: Guatemala City
country: Guatemala
city: Guatemala City
country: Guatemala
city: Hong Kong
country: Hong Kong
city: Hong Kong
country: Hong Kong
city: Arenzano
country: Italy
city: Bergamo
country: Italy
city: Catania
country: Italy
city: Cona (ferrara)
country: Italy
city: Genova
country: Italy
city: Napoli
country: Italy
city: Pavia
country: Italy
city: Pisa
country: Italy
city: Potenza
country: Italy
city: Reggio Emilia
country: Italy
city: Udine
country: Italy
city: Varese
country: Italy
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Culiacan
country: Mexico
city: Guadalajara
country: Mexico
city: Guadalajara
country: Mexico
city: Leon
country: Mexico
city: Merida
country: Mexico
city: Mexico Ctiy
country: Mexico
city: Miexico City
country: Mexico
city: Morelia
country: Mexico
city: Obregon
country: Mexico
city: Queretaro
country: Mexico
city: Saltillo
country: Mexico
city: Torreon
country: Mexico
city: Auckland
country: New Zealand
city: Hamilton
country: New Zealand
city: Tauranga
country: New Zealand
city: Wellington
country: New Zealand
city: Lima 01
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Cebu
country: Philippines
city: Manila
country: Philippines
city: Quezon
country: Philippines
city: Bialystok
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Ponce
country: Puerto Rico
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Iasi
country: Romania
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Ulyanovsk
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Singapore
country: Singapore
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Parktown
country: South Africa
city: Port Elizabeth
country: South Africa
city: Stellenbosch
country: South Africa
city: Barakaldo
country: Spain
city: Bilbao
country: Spain
city: La Coruna
country: Spain
city: La Laguna
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Merida
country: Spain
city: Santander
country: Spain
city: Santiago de Compostela
country: Spain
city: Sevilla
country: Spain
city: Torrelavega
country: Spain
city: Valencia
country: Spain
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Cambridge
country: United Kingdom
city: Cannock
country: United Kingdom
city: Coventry
country: United Kingdom
city: Eastbourne
country: United Kingdom
city: Exeter
country: United Kingdom
city: Harrogate
country: United Kingdom
city: Ipswich
country: United Kingdom
city: London
country: United Kingdom
city: Middlesborough
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Northampton
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Westcliffe-on-sea
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Burmester GR, Rubbert-Roth A, Cantagrel A, Hall S, Leszczynski P, Feldman D, Rangaraj MJ, Roane G, Ludivico C, Bao M, Rowell L, Davies C, Mysler EF. Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA). Ann Rheum Dis. 2016 Jan;75(1):68-74. doi: 10.1136/annrheumdis-2015-207281. Epub 2015 Jun 8.