Clinical trial NCT00750880: An Exploratory Study of Tocilizumab in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Current Non-Biologic DMARDs and/or Anti-TNF Therapy.
Official title: International Multi-Center Open Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs Who Have An Inadequate Response to Current Non-Biologic DMARD or Anti-TNF Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-09-11
Enrollment: 1681
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, single arm study will investigate the safety, tolerability and efficacy of tocilizumab monotherapy, or combination therapy with non-biologic disease modifying antirheumatic drugs (DMARDs), in patients with severe active RA. Patients will receive tocilizumab 8mg/kg iv as a 60 minute infusion 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 individuals.


Eligibility criteria: Inclusion Criteria:

* male and non-pregnant or nursing female patients \>=18 years of age;
* body weight \<=150kg;
* moderate to severe active RA (DAS28 \>=3.2) of \>=6 months duration;
* on \>=1 non-biologic DMARDs at a stable dose for a period of \>= 8 weeks prior to start of treatment;
* inadequate clinical response to a stable dose of non-biologic DMARD or anti-TNF therapy;
* if receiving oral corticosteroids, the dose must have been stable for at least 25 of 28 days prior to start of treatment.

Exclusion Criteria:

* major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment;
* rheumatic autoimmune disease other than RA;
* prior history of, or current inflammatory joint disease other than RA;
* functional class IV as defined by the ACR Classification of Functional Status in RA.

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs): Overall Summary
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
Secondary outcomes:
measure: Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Time to Low Disease Activity or Remission Based on DAS28 - Number of Participants With an Event
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Time to Low Disease Activity and Remission Based on DAS28 Score - Time to Event
timeFrame: Baseline,Weeks 4, 8, 12, 16, 20, and 24
measure: Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: DAS28 Scores by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response - Number of Participants With an Event
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Swollen Joint Count by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Tender Joint Count by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Patient's Global Assessment of Disease Activity by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Physician's Global Assessment of Disease Activity by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Patient's Global Assessment of Pain by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: C-Reactive Protein by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Erythrocyte Sedimentation Rate by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: HAQ-DI Scores by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Other outcomes:
Locations:
city: Canberra
country: Australia
state: Australian Capital Territory
city: Coffs Harbour
country: Australia
state: New South Wales
city: Kogarah
country: Australia
state: New South Wales
city: Parramatta Park
country: Australia
state: New South Wales
city: Adelaide
country: Australia
state: South Australia
city: Fitzroy
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state: Victoria
city: Geelong
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state: Victoria
city: Melbourne
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state: Victoria
city: Graz-Eggenberg
country: Austria
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Linz
country: Austria
city: Salzburg
country: Austria
city: Stockerau
country: Austria
city: Wien
country: Austria
city: Wien
country: Austria
city: Wien
country: Austria
city: Aalst
country: Belgium
city: Bruxelles
country: Belgium
city: Bruxelles
country: Belgium
city: Bruxelles
country: Belgium
city: Bruxelles
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Hasselt
country: Belgium
city: Heusy
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Merksem
country: Belgium
city: Montignies S/ Sambre
country: Belgium
city: Westmalle
country: Belgium
city: Edmonton
country: Canada
state: Alberta
city: Lethbridge
country: Canada
state: Alberta
city: Kelowna
country: Canada
state: British Columbia
city: Nanaimo
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Vancouver
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state: British Columbia
city: Quispamsis
country: Canada
state: New Brunswick
city: St John's
country: Canada
state: Newfoundland and Labrador
city: Hamilton
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
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state: Ontario
city: Toronto
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state: Ontario
city: Windsor
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state: Ontario
city: Laval
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state: Quebec
city: Montreal
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city: Montreal
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state: Quebec
city: Quebec City
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state: Quebec
city: Rimouski
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state: Saskatchewan
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city: St Brieuc
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city: Valence
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city: Berlin
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city: Hamburg
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city: Jena
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city: Kiel
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country: Germany
city: Saarbruecken
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country: Germany
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country: Germany
city: Athens
country: Greece
city: Heraklion
country: Greece
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country: Greece
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country: Greece
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city: Budapest
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city: Eger
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city: Bangalore
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city: Chennai
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city: Hyderabad
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city: Jaipur
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city: Kolkata
country: India
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country: Italy
city: Novara
country: Italy
city: Palermo
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city: Potenza
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city: Roma
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city: Roma
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city: Siena
country: Italy
city: Varese
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city: Luxembourg
country: Luxembourg
city: 'S Hertogenbosch
country: Netherlands
city: Alkmaar
country: Netherlands
city: Amsterdam
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city: Arnhem
country: Netherlands
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country: Netherlands
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city: Gouda
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city: Bucharest
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city: Cluj-napoca
country: Romania
city: Jeddah
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city: Elche
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state: Alicante
city: Elda
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city: Aviles
country: Spain
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city: Sabadell
country: Spain
state: Barcelona
city: Terrassa
country: Spain
state: Barcelona
city: VIC
country: Spain
state: Barcelona
city: Cádiz
country: Spain
state: Cadiz
city: Jerez de La Frontera
country: Spain
state: Cadiz
city: La Coruna
country: Spain
state: La Coruña
city: Las Palmas De Gran Canaria
country: Spain
state: Las Palmas
city: Ponferrada
country: Spain
state: Leon
city: La Laguna
country: Spain
state: Tenerife
city: Alicante
country: Spain
city: Almeria
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Caceres
country: Spain
city: Cordoba
country: Spain
city: Granada
country: Spain
city: Huesca
country: Spain
city: Leon
country: Spain
city: Lugo
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Murcia
country: Spain
city: Orense
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Tenerife
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Falun
country: Sweden
city: Huddinge
country: Sweden
city: Karlstad
country: Sweden
city: Linkoeping
country: Sweden
city: Malmo
country: Sweden
city: Skoevde
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Västerås
country: Sweden
city: Aarau
country: Switzerland
city: Basel
country: Switzerland
city: Fribourg
country: Switzerland
city: Genève
country: Switzerland
city: Luzern
country: Switzerland
city: St. Gallen
country: Switzerland
city: Zürich
country: Switzerland
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Barnsley
country: United Kingdom
city: Basingstoke
country: United Kingdom
city: Bournemouth
country: United Kingdom
city: Brighton
country: United Kingdom
city: Burton on Trent
country: United Kingdom
city: Bury St Edmonds
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Chelmsford
country: United Kingdom
city: Dudley
country: United Kingdom
city: Dundee
country: United Kingdom
city: Eastbourne
country: United Kingdom
city: Gillingham
country: United Kingdom
city: Harrogate
country: United Kingdom
city: Huddersfield
country: United Kingdom
city: Ipswich
country: United Kingdom
city: Liverpool
country: United Kingdom
city: Llantrisant
country: United Kingdom
city: Londonderry
country: United Kingdom
city: London
country: United Kingdom
city: Maidstone
country: United Kingdom
city: Middlesborough
country: United Kingdom
city: Newcastle upon Tyne
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Reading
country: United Kingdom
city: Salford
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southport
country: United Kingdom
city: Swindon
country: United Kingdom
city: Torquay
country: United Kingdom
city: Westcliffe-on-sea
country: United Kingdom
city: Wirral
country: United Kingdom
city: Worthing
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: