Trial Outcomes & Findings for 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. (NCT NCT01195272)
NCT ID: NCT01195272
Last Updated: 2014-11-13
Results Overview
Aging neutrophils translocate phosphatidylserine from the inner leaflet of the plasma membrane to the outer leaflet during the early stages of apoptosis. This translocation can be measured due to the affinity of fluorescein isothiocyanate (FITC)-labeled annexin V to bind exposed phosphatidylserine. Cells that stain positive to Annexin V binding are apoptotic. At 4 hours (hrs) and 20 hrs stimulated and control samples were analyzed for levels of apoptosis.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
21 participants
Primary outcome timeframe
Visits 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)
Results posted on
2014-11-13
Participant Flow
Participant milestones
| Measure |
Tocilizumab 8 Milligrams Per Kilogram (mg/kg)
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) intravenously (IV), once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Overall Study
STARTED
|
21
|
|
Overall Study
COMPLETED
|
17
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Tocilizumab 8 Milligrams Per Kilogram (mg/kg)
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) intravenously (IV), once every 4 weeks up to 52 weeks (total of 13 infusions).
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|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Lack of Efficacy
|
3
|
Baseline Characteristics
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.
Baseline characteristics by cohort
| Measure |
Tocilizumab 8 mg/kg
n=21 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Age, Continuous
|
49.2 Years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Visits 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)Population: Intent-to-treat (ITT) Population: all participants in the Safety Population who provided follow-up data for neutrophils or at least 1 efficacy variable. n (number) equals (=) number of participants analyzed for the specified parameter at a given visit.
Aging neutrophils translocate phosphatidylserine from the inner leaflet of the plasma membrane to the outer leaflet during the early stages of apoptosis. This translocation can be measured due to the affinity of fluorescein isothiocyanate (FITC)-labeled annexin V to bind exposed phosphatidylserine. Cells that stain positive to Annexin V binding are apoptotic. At 4 hours (hrs) and 20 hrs stimulated and control samples were analyzed for levels of apoptosis.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
Visit 8, 20 hrs (n=15)
|
48.24 percentage of cells staining positive
Standard Deviation 10.37
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
Visit 2, 4 hrs (n=19)
|
8.95 percentage of cells staining positive
Standard Deviation 5.46
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
Visit 3, 4 hrs (n=19)
|
7.36 percentage of cells staining positive
Standard Deviation 4.18
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
Visit 5, 4 hrs (n=19)
|
8.45 percentage of cells staining positive
Standard Deviation 4.64
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
Visit 8, 4 hrs (n=15)
|
12.43 percentage of cells staining positive
Standard Deviation 6.34
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
Visit 2, 20 hrs (n=19)
|
53.97 percentage of cells staining positive
Standard Deviation 8.97
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
Visit 3, 20 hrs (n=19)
|
50.32 percentage of cells staining positive
Standard Deviation 10.64
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis
Visit 5, 20 hrs (n=19)
|
50.50 percentage of cells staining positive
Standard Deviation 15.51
|
PRIMARY outcome
Timeframe: Visits 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Aging neutrophils translocate phosphatidylserine from the inner leaflet of the plasma membrane to the outer leaflet during the early stages of apoptosis. This translocation can be measured due to the affinity of FITC-labeled annexin V to bind exposed phosphatidylserine. Cells that stain positive to Annexin V binding are apoptotic. At 4 hrs and 20 hrs stimulated and control samples were analyzed for levels of apoptosis. GM-CSF is an agent that delays apoptosis. Percentage of cells that stained positive for Annexin V binding in the presence or absence of GM-CSF (GM-CSF delayed or constitutive) were determined by flow cytometry.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
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|---|---|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Visit 2, 4 hrs (n=19)
|
5.46 percentage of cells staining positive
Standard Deviation 6.73
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Visit 3, 4 hrs (n=19)
|
4.18 percentage of cells staining positive
Standard Deviation 7.13
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Visit 5, 4 hrs (n=19)
|
4.64 percentage of cells staining positive
Standard Deviation 3.18
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Visit 8, 4 hrs (n=15)
|
6.34 percentage of cells staining positive
Standard Deviation 2.58
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Visit 2, 20 hrs (n=19)
|
27.00 percentage of cells staining positive
Standard Deviation 11.16
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Visit 3, 20 hrs (n=19)
|
28.35 percentage of cells staining positive
Standard Deviation 10.95
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Visit 5, 20 hrs (n=19)
|
29.68 percentage of cells staining positive
Standard Deviation 14.78
|
|
Mean Percentage of Cells Staining Positive for Annexin V Binding With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Visit 8, 20 hrs (n=15)
|
27.79 percentage of cells staining positive
Standard Deviation 12.01
|
PRIMARY outcome
Timeframe: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Neutrophils were incubated with labeled antibodies against CD11b. Flow cytometry was used to determine the mean fluorescence intensity. Greater fluorescence correlates with greater adhesion, migration, and ingestion of complement-opsonized particles.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Fluorescence Intensity of CD11b on Neutrophil Surface
Visit 2 (n=19)
|
286.40 fluorescence intensity unit
Standard Deviation 105.86
|
|
Mean Fluorescence Intensity of CD11b on Neutrophil Surface
Visit 3 (n=17)
|
275.33 fluorescence intensity unit
Standard Deviation 127.37
|
|
Mean Fluorescence Intensity of CD11b on Neutrophil Surface
Visit 5 (n=16)
|
240.93 fluorescence intensity unit
Standard Deviation 77.50
|
PRIMARY outcome
Timeframe: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)Population: ITT Population; n=number of participants analyzed at each visit
Neutrophils were incubated with labeled antibodies against CD18. Flow cytometry was used to determine the mean fluorescence intensity. Greater fluorescence correlates with greater adhesion, migration, and ingestion of complement-opsonized particles.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Fluorescence Intensity of CD18 on Neutrophil Surface
Visit 2 (n=19)
|
20.33 fluorescence intensity unit
Standard Deviation 8.30
|
|
Mean Fluorescence Intensity of CD18 on Neutrophil Surface
Visit 3 (n=17)
|
20.47 fluorescence intensity unit
Standard Deviation 12.31
|
|
Mean Fluorescence Intensity of CD18 on Neutrophil Surface
Visit 5 (n=16)
|
22.47 fluorescence intensity unit
Standard Deviation 15.42
|
PRIMARY outcome
Timeframe: Visits 2, 3 and 5 (Baseline and Weeks 4 and 12)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Neutrophils were incubated with labeled antibody against CD62L (L selectin). Flow cytometry was used to determine the mean fluorescence intensity. Greater fluorescence correlates with greater adhesion of neutrophils to vessel walls.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Fluorescence Intensity of CD62L (L Selectin) on Neutrophil Surface
Visit 2 (n=19)
|
20.56 fluorescence intensity unit
Standard Deviation 10.05
|
|
Mean Fluorescence Intensity of CD62L (L Selectin) on Neutrophil Surface
Visit 3 (n=17)
|
23.40 fluorescence intensity unit
Standard Deviation 11.55
|
|
Mean Fluorescence Intensity of CD62L (L Selectin) on Neutrophil Surface
Visit 5 (n=16)
|
19.93 fluorescence intensity unit
Standard Deviation 15.32
|
PRIMARY outcome
Timeframe: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Neutrophils were incubated with labeled antibody against CD63b. Flow cytometry was used to determine the mean fluorescence intensity. Greater fluorescence correlates with greater azurophilic degranulation, an indicator of greater microbe killing.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Fluorescence Intensity of CD63 on Neutrophil Surface
Visit 2 (n=19)
|
31.00 fluorescence intensity unit
Standard Deviation 20.68
|
|
Mean Fluorescence Intensity of CD63 on Neutrophil Surface
Visit 3 (n=17)
|
26.34 fluorescence intensity unit
Standard Deviation 14.55
|
|
Mean Fluorescence Intensity of CD63 on Neutrophil Surface
Visit 5 (n=16)
|
30.28 fluorescence intensity unit
Standard Deviation 16.53
|
PRIMARY outcome
Timeframe: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Neutrophils were incubated with labeled antibody against IL-6R. Flow cytometry was used to determine the mean fluorescence intensity. Greater fluorescence correlates with greater density of membrane bound IL-6 receptor.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Fluorescence Intensity of Interleukin-6 Receptor (Il-6R) on Neutrophil Surface
Visit 2 (n=19)
|
2.72 fluorescence intensity unit
Standard Deviation 1.50
|
|
Mean Fluorescence Intensity of Interleukin-6 Receptor (Il-6R) on Neutrophil Surface
Visit 3 (n=17)
|
3.69 fluorescence intensity unit
Standard Deviation 1.97
|
|
Mean Fluorescence Intensity of Interleukin-6 Receptor (Il-6R) on Neutrophil Surface
Visit 5 (n=16)
|
4.42 fluorescence intensity unit
Standard Deviation 2.55
|
PRIMARY outcome
Timeframe: Visits 2, 3, and 5 (Baseline and Weeks 4 and 12)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Neutrophils were incubated with labeled antibody against mTNF. Flow cytometry was used to determine the mean fluorescence intensity. Greater fluorescence correlates to a greater density of membrane bound TNF.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Fluorescence Intensity of Membrane Bound Tumor Necrosis Factor Alpha (mTNFα) on Neutrophil Surface
Visit 2 (n=19)
|
3.49 fluorescence intensity unit
Standard Deviation 3.32
|
|
Mean Fluorescence Intensity of Membrane Bound Tumor Necrosis Factor Alpha (mTNFα) on Neutrophil Surface
Visit 3 (n=17)
|
3.55 fluorescence intensity unit
Standard Deviation 3.29
|
|
Mean Fluorescence Intensity of Membrane Bound Tumor Necrosis Factor Alpha (mTNFα) on Neutrophil Surface
Visit 5 (n=16)
|
3.75 fluorescence intensity unit
Standard Deviation 4.85
|
PRIMARY outcome
Timeframe: Visit 2, 3, 5, and 8 (Baseline and predose at Weeks 4, 12 and 24)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Using luminol as a substrate for reactive oxidants, a chemical reaction is produced resulting in photon emission (chemiluminescence). fMLP stimulation is mediated through the fMLP receptor on the cell surface. The fMLP response is only observed in primed neutrophils and response is a measure of in vivo priming. Measurements of reactive oxygen species are calculated as total chemiluminescence or the AUC.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Chemiluminescence (Area Under the Concentration-time Curve [AUC]) of Neutrophil Reactive Species Production Using Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) Stimulation
Visit 2 (n=19)
|
8671 chemiluminescence units*hours
Standard Deviation 4597.18
|
|
Mean Chemiluminescence (Area Under the Concentration-time Curve [AUC]) of Neutrophil Reactive Species Production Using Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) Stimulation
Visit 3 (n=18)
|
9971 chemiluminescence units*hours
Standard Deviation 7139.36
|
|
Mean Chemiluminescence (Area Under the Concentration-time Curve [AUC]) of Neutrophil Reactive Species Production Using Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) Stimulation
Visit 5 (n=17)
|
32361 chemiluminescence units*hours
Standard Deviation 72947.87
|
|
Mean Chemiluminescence (Area Under the Concentration-time Curve [AUC]) of Neutrophil Reactive Species Production Using Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) Stimulation
Visit 8 (n=14)
|
10573 chemiluminescence units*hours
Standard Deviation 5537.06
|
PRIMARY outcome
Timeframe: Visit 2, 3, 5, and 8 (Baseline and predose at Weeks 4, 12 and 24)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Using luminol as a substrate for reactive oxidants, a chemical reaction is produced resulting in photon emission (chemiluminescence). PMA is a receptor-independent stimulator of the respiratory burst and the PMA response measures the total capacity of neutrophils to generate reactive oxidants. Measurements of reactive oxygen species are calculated as total chemiluminescence or the AUC.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Mean Chemiluminescence (AUC) of Neutrophil Reactive Species Production Using Phorbol 12-Myristate 13-Acetate (PMA) Stimulation
Visit 2 (n=19)
|
141039 chemiluminescence units * hours
Standard Deviation 72621.95
|
|
Mean Chemiluminescence (AUC) of Neutrophil Reactive Species Production Using Phorbol 12-Myristate 13-Acetate (PMA) Stimulation
Visit 3 (n=18)
|
145304 chemiluminescence units * hours
Standard Deviation 48836.93
|
|
Mean Chemiluminescence (AUC) of Neutrophil Reactive Species Production Using Phorbol 12-Myristate 13-Acetate (PMA) Stimulation
Visit 5 (n=17)
|
157028 chemiluminescence units * hours
Standard Deviation 73054.72
|
|
Mean Chemiluminescence (AUC) of Neutrophil Reactive Species Production Using Phorbol 12-Myristate 13-Acetate (PMA) Stimulation
Visit 8 (n=14)
|
116968 chemiluminescence units * hours
Standard Deviation 51291.31
|
PRIMARY outcome
Timeframe: Visit 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
S. aureus were heat killed then labeled with PI and opsonized with AB serum (SAPI). S. aureus was then incubated with the neutrophils for 30 minutes at 37 degrees Celsius. The neutrophils were washed, then the percentage of cells positive for the labeled S. aureus (that is, phagocytosed) was calculated via flow cytometry. A higher percentage represented more active phagocytosis.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Percentage of Neutrophils Positive for Propidium Iodide (PI)-Labeled Staphylococcus Aureus (S. Aureus) Uptake
Visit 2 (n=19)
|
96.59 percentage of positive neutrophils
Standard Deviation 3.01
|
|
Percentage of Neutrophils Positive for Propidium Iodide (PI)-Labeled Staphylococcus Aureus (S. Aureus) Uptake
Visit 3 (n=19)
|
97.47 percentage of positive neutrophils
Standard Deviation 2.56
|
|
Percentage of Neutrophils Positive for Propidium Iodide (PI)-Labeled Staphylococcus Aureus (S. Aureus) Uptake
Visit 5 (n=17)
|
97.53 percentage of positive neutrophils
Standard Deviation 2.68
|
|
Percentage of Neutrophils Positive for Propidium Iodide (PI)-Labeled Staphylococcus Aureus (S. Aureus) Uptake
Visit 8 (n=15)
|
97.25 percentage of positive neutrophils
Standard Deviation 2.27
|
PRIMARY outcome
Timeframe: Visit 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24)Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Phagocytosis can be measured by incubating neutrophils with PI-labeled heat killed S. aureus following incubation for 30 minutes. Neutrophils are co-incubated with DHR, which becomes oxidized by the products of the respiratory burst generated during phagocytosis. Fluorescence can then be measured by flow cytometry.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=19 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Percentage of Neutrophils Positive for Dihydrorhodamine-123 (DHR) Oxidation
Visit 2 (n=19)
|
99.21 percentage of positive neutrophils
Standard Deviation 2.43
|
|
Percentage of Neutrophils Positive for Dihydrorhodamine-123 (DHR) Oxidation
Visit 3 (n=19)
|
99.20 percentage of positive neutrophils
Standard Deviation 1.93
|
|
Percentage of Neutrophils Positive for Dihydrorhodamine-123 (DHR) Oxidation
Visit 5 (n=17)
|
99.91 percentage of positive neutrophils
Standard Deviation 0.18
|
|
Percentage of Neutrophils Positive for Dihydrorhodamine-123 (DHR) Oxidation
Visit 8 (n=15)
|
99.92 percentage of positive neutrophils
Standard Deviation 0.22
|
SECONDARY outcome
Timeframe: Screening, Baseline, and Weeks 4, 8, 12, 16, 20, 24, 36, 48, and 52Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index includes swollen and tender joint counts, acute phase response (erythrocyte sedimentation rate \[ESR\] or C-reactive protein \[CRP\]), and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS, which includes a 44 swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=21 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Screening (n=21)
|
5.67 score on a scale
Standard Deviation 1.22
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Baseline (n=21)
|
6.15 score on a scale
Standard Deviation 1.26
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 4 (n=21)
|
4.90 score on a scale
Standard Deviation 1.40
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 8 (n=20)
|
4.31 score on a scale
Standard Deviation 1.64
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 12 (n=20)
|
3.83 score on a scale
Standard Deviation 1.45
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 16 (n=20)
|
3.81 score on a scale
Standard Deviation 1.69
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 20 (n=20)
|
3.92 score on a scale
Standard Deviation 1.45
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 24 (n=16)
|
3.26 score on a scale
Standard Deviation 1.49
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 36 (n=12)
|
3.27 score on a scale
Standard Deviation 1.33
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 48 (n=11)
|
3.59 score on a scale
Standard Deviation 1.62
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 52 (n=18)
|
3.58 score on a scale
Standard Deviation 1.51
|
SECONDARY outcome
Timeframe: Weeks 12, 24, and 36Population: ITT Population; n=number of participants analyzed for the specified parameter at a given visit.
Benefit:Risk was defined at the participant level. It was considered acceptable if the DAS28 improvement represented at least a moderate European League Against Rheumatism (EULAR) response. The risks were based on the known adverse event (AE) profile of tocilizumab rather than on the actual AEs experienced by each participant
Outcome measures
| Measure |
Tocilizumab 8 mg/kg
n=20 Participants
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Percentage of Participants With Acceptable and Not Acceptable Benefit-Risk Assessments
Acceptable, Week 12
|
100 percentage of participants
|
|
Percentage of Participants With Acceptable and Not Acceptable Benefit-Risk Assessments
Not Acceptable, Week 12
|
0 percentage of participants
|
|
Percentage of Participants With Acceptable and Not Acceptable Benefit-Risk Assessments
Acceptable, Week 24
|
94 percentage of participants
|
|
Percentage of Participants With Acceptable and Not Acceptable Benefit-Risk Assessments
Not Acceptable, Week 24
|
6 percentage of participants
|
|
Percentage of Participants With Acceptable and Not Acceptable Benefit-Risk Assessments
Acceptable, Week 36
|
92 percentage of participants
|
|
Percentage of Participants With Acceptable and Not Acceptable Benefit-Risk Assessments
Not Acceptable, Week 36
|
8 percentage of participants
|
Adverse Events
Tocilizumab 8 mg/kg
Serious events: 4 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tocilizumab 8 mg/kg
n=21 participants at risk
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Pneumonia Viral
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Injury, poisoning and procedural complications
Hip Fracture
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
Other adverse events
| Measure |
Tocilizumab 8 mg/kg
n=21 participants at risk
Participants received tocilizumab 8 mg/kg (maximum dose 800 mg) IV, once every 4 weeks up to 52 weeks (total of 13 infusions).
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
9.5%
2/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Ear infection
|
14.3%
3/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Lower respiratory tract infection
|
42.9%
9/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Nasopharyngitis
|
38.1%
8/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Urinary tract infection
|
14.3%
3/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Constipation
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
7/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Dry mouth
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Dyspepsia
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Mouth ulceration
|
14.3%
3/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Nausea
|
14.3%
3/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
General disorders
Fatigue
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
General disorders
Malaise
|
14.3%
3/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Investigations
Neutrophil count decreased
|
9.5%
2/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Joint lock
|
9.5%
2/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
9.5%
2/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.3%
3/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
47.6%
10/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Nervous system disorders
Headache
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
3/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
19.0%
4/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
9.5%
2/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.3%
3/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Vascular disorders
Hypertension
|
9.5%
2/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Vascular disorders
Peripheral coldness
|
9.5%
2/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Cardiac disorders
Palpitations
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Endocrine disorders
Cushingoid
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Abdominal pain
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Abdominal tenderness
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Gastric ulcer
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
General disorders
Chest pain
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Candidiasis
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Cystitis
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Eye infection
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Herpes simplex
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Herpes zoster
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Pneumonia
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Sinusitis
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Infections and infestations
Tooth abscess
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Injury, poisoning and procedural complications
Fall
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Investigations
Blood cholesterol increased
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Axillary mass
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Nervous system disorders
Dizziness
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Nervous system disorders
Dysgeusia
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Nervous system disorders
Sciatica
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Psychiatric disorders
Anxiety
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Psychiatric disorders
Depression
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Psychiatric disorders
Insomnia
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Renal and urinary disorders
Dysuria
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Heat rash
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Pruritus allergic
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Vascular disorders
Hot flush
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
|
Vascular disorders
Vasculitis
|
4.8%
1/21 • Adverse events were recorded from the date of Screening until the End of Study which was the follow up visit after 48 Weeks of extension treatment period.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but only after the first publication or presentation that involves the overall study. The sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER