Clinical trial NCT01195272: A Study of the Effects of RoActemra/Actemra (Tocilizumab) on Neutrophils in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic and/or Non-biologic DMARDs.
Official title: A 52 Week, Single Center, Open-label Study to Evaluate Neutrophil Function and Survival Effects of Tocilizumab (TCZ) in Patients With Active Rheumatoid Arthritis (RA) on Background Non-biologic DMARDs Who Have an Inadequate Response to Current Non-biologic DMARD and/or Anti-TNF Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-09-06
Enrollment: 21
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 assess the effect of RoActemra/Actemra (tocilizumab) on neutrophils and monitor safety and benefit-risk of RoActemra/Actemra treatment in patients with active rheumatoid arthritis who have an inadequate response to current biologic or non-biologic disease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Actemra at a dose of 8 mg/kg intravenously every 4 weeks, either as monotherapy or in combination with their current non-biologic DMARD. Anticipated time on study treatment is 52 weeks.


Eligibility criteria: Inclusion Criteria:

* Adult patients, \>/= 18 years of age
* Moderate to severe active rheumatoid arthritis of \>/= 6 months duration
* DAS28 \>/= 3.2 at screening and baseline
* Inadequate response to biologic or non-biologic DMARDs
* Biologic DMARDs must be withdrawn (approximately 5 half-lives for the agent) before first dose of study drug
* If continuing on a non-biologic DMARD, dose should be stable for at least 8 weeks
* Oral corticosteroids must have been at stable dose for at least 25 out of 28 days prior to baseline

Exclusion Criteria:

* Major surgery (including joint surgery) within 8 weeks prior to screening or not recovered from prior surgery
* Rheumatic autoimmune disease other then RA
* Functional class IV as defined by the American College of Rheumatology (ACR) classification
* Prior history of or current inflammatory joint disease other than RA
* Previous treatment with any cell-depleting therapies
* Intraarticular or parenteral corticosteroids within 4 weeks prior to baseline
* Active infection or history of recurrent infection
* Positive for HIV or hepatitis B or C
* History of or current primary or secondary immunodeficiency

Primary outcomes:
measure: Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
timeFrame: Visits 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)
measure: Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
timeFrame: Visits 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)
measure: Mean Fluorescence Intensity of CD11b on Neutrophil Surface
timeFrame: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)
measure: Mean Fluorescence Intensity of CD18 on Neutrophil Surface
timeFrame: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)
measure: Mean Fluorescence Intensity of CD62L (L Selectin) on Neutrophil Surface
timeFrame: Visits 2, 3 and 5 (Baseline and Weeks 4 and 12)
measure: Mean Fluorescence Intensity of CD63 on Neutrophil Surface
timeFrame: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)
measure: Mean Fluorescence Intensity of Interleukin-6 Receptor (Il-6R) on Neutrophil Surface
timeFrame: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)
measure: Mean Fluorescence Intensity of Membrane Bound Tumor Necrosis Factor Alpha (mTNFα) on Neutrophil Surface
timeFrame: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)
measure: Mean Chemiluminescence (Area Under the Concentration-time Curve [AUC]) of Neutrophil Reactive Species Production Using Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) Stimulation
timeFrame: Visit 2, 3, 5, and 8 (Baseline and predose at Weeks 4, 12 and 24)
measure: Mean Chemiluminescence (AUC) of Neutrophil Reactive Species Production Using Phorbol 12-Myristate 13-Acetate (PMA) Stimulation
timeFrame: Visit 2, 3, 5, and 8 (Baseline and predose at Weeks 4, 12 and 24)
measure: Percentage of Neutrophils Positive for Propidium Iodide (PI)-Labeled Staphylococcus Aureus (S. Aureus) Uptake
timeFrame: Visit 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)
measure: Percentage of Neutrophils Positive for Dihydrorhodamine-123 (DHR) Oxidation
timeFrame: Visit 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)
Secondary outcomes:
measure: Disease Activity Score Based on 28-Joint Count (DAS28)
timeFrame: Screening, Baseline, and Weeks 4, 8, 12, 16, 20, 24, 36, 48, and 52
measure: Percentage of Participants With Acceptable and Not Acceptable Benefit-Risk Assessments
timeFrame: Weeks 12, 24, and 36
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: