Clinical trial NCT00721123: A Long-term Extension Study of Tocilizumab (Myeloma Receptor Antibody [MRA]) in Patients With Rheumatoid Arthritis
Official title: Long-term Extension Study of Safety During Treatment With Tocilizumab (MRA) in Patients Completing Treatment in WA17822
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-07-23
Enrollment: 538
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, international multi-center extension study WA18695 was designed to assess the long term safety of tocilizumab in patients who had moderate to severe active rheumatoid arthritis (RA). Patients enrolled in the WA18695 study had previously received treatment in the 24-week, placebo-controlled, Phase III Study WA17822. Eligible patients were assigned to treatment with 8 mg/kg tocilizumab every 4 weeks for a maximum of 5 years.

Detailed description: The primary objective of this extension study was to assess the long-term safety of 8 mg/kg tocilizumab with regard to adverse events (AEs) and laboratory result abnormalities.

The secondary objectives were as follows:

* To explore the possibility of reducing concomitant steroid treatment
* To determine the long-term efficacy of 8 mg/kg tocilizumab with regard to reduction in signs and symptoms
* To better understand and predict tocilizumab efficacy, response, safety, and progression of rheumatoid arthritis (RA) and associated diseases with regard to its effect on biomarkers

No viable biomarkers for TCZ treatment effects were identified from the controlled studies. There were, therefore, no biomarkers that warranted further investigation in long-term studies, so no biomarker data are reported.

The extension study WA18695 was an open-label, international multi-center study in patients with moderate to severe active rheumatoid arthritis (RA) who had completed treatment in the 24 weeks placebo-controlled Phase III study WA17822. Patients entering WA17822 had an inadequate response to methotrexate (MTX), and, during WA17822, patients had received treatment with intravenous infusions of tocilizumab 4 mg/kg, 8 mg/kg, or placebo every 4 weeks with background MTX therapy.

All patients who completed the planned course of treatment or escape therapy in the WA17822 study were eligible to enter the WA18695 long-term extension study, where they were assigned to treatment with 8 mg/kg RoActemra/Actemra plus MTX. The dose of RA medications such as MTX and nonsteroidal anti-inflammatory drugs (NSAIDs), but excluding corticosteroids, was to be kept stable for the first 48 weeks of the WA18695 study. During this time dose reductions in these treatments were only allowed as clinically required for safety reasons. After week 48, the administration of disease-modifying antirheumatic drugs (DMARDs) and NSAIDs could be changed, according to the investigator's practice and as tolerated by the patient.

Eligibility criteria: Inclusion Criteria:

* Patients who have completed participation in the Phase III study WA17822 (NCT00106548) in adult rheumatoid arthritis.

Exclusion Criteria:

* Treatment with any investigational agent since the last administration of study drug in WA17822.
* Treatment with intravenous (IV) gammaglobulin, plasmapheresis, or Prosorba column since the last administration of study drug in WA17822.
* Treatment with an anti-tumor necrosis factor or anti-interleukin-1 agent, or a T cell costimulation modulator since the last administration of study drug in WA17822.
* Previous treatment with any cell-depleting therapies.
* Parenteral, intramuscular, or intra-articular corticosteroids within 6 weeks prior to baseline.

Primary outcomes:
measure: Adverse Event (AE) Summary Over Time
timeFrame: through 264 Weeks
measure: Summary Adverse Event Rates Over Time
timeFrame: through 264 Weeks
measure: Overall Death Rate Over Time
timeFrame: through 264 Weeks
Secondary outcomes:
measure: Participants Showing Improvement in Rheumatoid Arthritis Symptoms Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Percentage of Participants Classified as Responders by Disease Activity Scores Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Percentage of Participants Classified as Responders by EULAR Response Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Change From Baseline in Scores for Swollen and Tender Joint Counts Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Change From Baseline in Scores for Health Assessment Questionnaire - Disability Index Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Change From Baseline in Scores for Patient's Global Assessment of Disease Activity Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Change From Baseline in Scores for Physician's Global Assessment of Disease Activity Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Change From Baseline in Scores for Patient's Level of Pain Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Measure for Fatigue Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
measure: Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Using the 36-Item Short-Form Health Survey (SF-36) Over Time, Through 264 Weeks
timeFrame: through 264 Weeks
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Adelaide
country: Australia
city: Maroochydore
country: Australia
city: Shenton Park
country: Australia
city: Wien
country: Austria
city: Wien
country: Austria
city: Wien
country: Austria
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: St John's
country: Canada
state: Newfoundland and Labrador
city: Burlington
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Sainte-foy
country: Canada
state: Quebec
city: Besancon
country: France
city: Creteil
country: France
city: Le Mans
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Bad Bramstedt
country: Germany
city: Bad Nauheim
country: Germany
city: Baden-baden
country: Germany
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Heidelberg
country: Germany
city: Koeln
country: Germany
city: Hong Kong
country: Hong Kong
city: Hong Kong
country: Hong Kong
city: Tuen Mun
country: Hong Kong
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Pécs
country: Hungary
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Cona (ferrara)
country: Italy
city: Gazzi
country: Italy
city: Palermo
country: Italy
city: Siena
country: Italy
city: Udine
country: Italy
city: Chihuahua
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico City
country: Mexico
city: Mexico City
country: Mexico
city: Mexico
country: Mexico
city: San Luis Potosi
country: Mexico
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Piestany
country: Slovakia
city: Bern
country: Switzerland
city: Lausanne
country: Switzerland
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: