Giant Cell Arteritis
Conditions
Brief summary
This multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of tocilizumab in participants with GCA. The study will consist of 2 parts: a 52-week double-blind treatment period (Part 1) followed by a 104-week open label long-term follow-up period (Part 2). In Part 1 of the study eligible participants will be randomized to receive either tocilizumab every week (qw) or every 2 weeks (q2w) or placebo for 52 weeks, with tapering oral daily doses of prednisone. After Week 52, participants in remission will stop study treatment and enter long-term follow-up, whereas participants with disease activity or flares will receive open-label tocilizumab or other treatment at the discretion of the investigator for a maximum period of 104 weeks.
Interventions
DRUGTocilizumab
Tocilizumab will be administered at a dose of 162 mg as SC injection qw or q2w for 52 weeks in Part 1 of the study and at a dose 162 mg as SC injection qw for 104 week at the discretion of the investigator in Part 2 of the study.
DRUGPrednisone
Prednisone will be administered at tapering oral doses as tablets daily for 26 or 52 weeks according to the protocol-defined schedule in Part 1 of the study. Prednisone will also be administered as escape therapy to treat disease flares in an open-label manner during Part 1 at a dose and duration selected by the investigator.
DRUGTocilizumab Placebo
Tocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study.
Prednisone placebo will be administered as tablets orally daily according to the protocol-defined schedule (from Week 26 to Week 52) in Part 1 of the study.
DRUGCorticosteroids
Participants without sustained remission at Week 52 will receive corticosteroids at a dose and schedule at the discretion of the investigator for a maximum of 104 weeks.
DRUGMethotrexate
Participants without sustained remission at Week 52 will receive methotrexate at a dose and schedule at the discretion of the investigator for a maximum of 104 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of GCA classified according to age \>/=50 years; history of ESR \>/=50 mm/hr or history of CRP \>/=2.45 mg/dL; and at least one of the following: unequivocal cranial symptoms of GCA or symptoms of polymyalgia rheumatica \[PMR\]; and at least one of the following: temporal artery biopsy revealing features of GCA or evidence of large-vessel vasculitis by angiography or cross-sectional imaging * New onset (diagnosis within 6 weeks of baseline) or refractory (diagnosis greater than \[\>\] 6 weeks before baseline and previous treatment with \>/= 40 milligrams per day prednisone \[or equivalent\] for at least 2 consecutive weeks at any time) GCA * Active disease (presence of clinical signs and symptoms \[cranial or PMR\] and ESR \>/=30 mm/hour or CRP \>/=1 mg/dL) within 6 weeks of baseline visit
Exclusion criteria
* Major surgery within 8 weeks prior to screening or planned within 12 months after randomization * Transplanted organs (except corneas with transplant performed \>3 months prior to screening) * Major ischemic event, unrelated to GCA, within 12 weeks of screening * Prior treatment with any of the following: investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening; cell-depleting therapies including investigational agent; intravenous (IV) gamma globulin or plasmapheresis within 6 months of baseline; alkylating agents or with total lymphoid irradiation; tocilizumab; hydroxychloroquine, cyclosporine A, azathioprine, or mycophenolate mofetil within 4 weeks of baseline; etanercept within 2 weeks of baseline; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks of baseline; anakinra within 1 week of baseline; tofacitinib; cyclophosphamide within 6 months of baseline; \>100 milligrams of daily IV methylprednisolone within 6 weeks of baseline * Participants requiring systemic glucocorticoids for conditions other than GCA, which, in the opinion of the investigator, would interfere with adherence to the fixed glucocorticoid taper regimen and/or to assessment of efficacy in response to the test article * History of severe allergic reactions to monoclonal antibodies or to prednisone * Evidence of serious uncontrolled concomitant disease (for example, cardiovascular, respiratory, renal, endocrine, psychiatric, corneal ulcers/injuries, or gastrointestinal \[GI\] disease) * Current liver disease, as determined by the investigator * History of diverticulitis, inflammatory bowel disease, or other symptomatic GI tract condition that might predispose to bowel perforation * Known active or history of recurrent bacterial, viral fungal, mycobacterial, or other infection * Primary or secondary immunodeficiency * Evidence of malignancies diagnosed within previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that have been excised and cured) * Inadequate hematologic, renal or liver function * Positive for hepatitis B or hepatitis C infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper) | Week 52 | Remission was defined as the absence of flare and normalization of the C-reactive protein (CRP) (less than \[\<\] 1 milligram per deciliter \[mg/dL\]). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) attributable to GCA. A single CRP elevation (\>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (\>/=1 mg/dL) at the next study visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First GCA Disease Flare | Up to 52 weeks | Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR \>/=30 mm/hr attributable to GCA. Participants who withdrew from the study prior to Week 52 were censored from the time of withdrawal. |
| Total Cumulative Prednisone Dose | Up to 52 weeks | The median total cumulative prednisone dose over the 52 weeks for each treatment group and the corresponding 95% confidence intervals are presented. |
| Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | Baseline, Week 52 | The SF-36 is a standardized questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical Component Score (PCS) and Mental Component Score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). A positive change from baseline indicates improvement. No imputation was used for missing data. Data was set to missing for participants who received escape therapy. |
| Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Baseline, Week 52 | Participants assessed their current disease activity on a 0-100 millimeter (mm) VAS, where 0 mm = no disease activity and 100 mm = maximum disease activity. A negative change from baseline indicates improvement. |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab | Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0]) | AUCtau is the model-predicted area under the tocilizumab serum concentration versus time curve from time zero to the end of dosing interval. AUCtau is measured in microgram\*day per milliliter (mcg\*day/mL). |
| Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab | Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0]) | Cmax,ss is maximum model-predicted serum steady state concentration of tocilizumab measured in micrograms per milliliter (mcg/mL). |
| Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper) | Week 52 | Remission was defined as the absence of flare and normalization of the CRP (\<1 mg/dL). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR \>/=30 mm/hr attributable to GCA. A single CRP elevation (\>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (\>/=1 mg/dL) at the next study visit. |
| Minimum Observed Serum Concentration (Ctrough) of Tocilizumab | Predose (Hour 0) at Baseline and Week 52 | Ctrough is minimum observed serum concentration of tocilizumab measured in mcg/mL. |
| Serum Interleukin-6 (IL-6) Level | Baseline and Week 52 | — |
| Serum Soluble IL-6 Receptor (sIL-6R) Level | Baseline and Week 52 | — |
| Erythrocyte Sedimentation Rate (ESR) | Baseline and Week 52 | ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation. |
| C-Reactive Protein (CRP) Level | Baseline and Week 52 | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. |
| Percentage of Participants With Anti-Tocilizumab Antibodies | Baseline up to Week 52 | All samples were tested by screening assay, and those samples that were positive were further analyzed by a confirmation assay to confirm specificity. Percentage of participants who has a positive confirmation assay result any time after the initial drug administration with a negative confirmation assay result at baseline was reported. |
| Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab | Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0]) | Cmin,ss is minimum model-predicted serum steady state concentration of tocilizumab measured in mcg/mL. |
Countries
Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study consists of 2 parts: a 52-week double-blind treatment period (Part 1) followed by a 104-week open label long-term follow-up period (Part 2).
Pre-assignment details
Of the 363 participants screened, a total of 251 participants were randomized into the study. One participant who was randomized to the Tocilizumab q2w + 26 weeks prednisone taper group withdrew on the same day of randomization and did not receive any study treatment. This participant was not included in any of the study analyses.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. | 100 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. | 49 |
| Part 1: Placebo + 26 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. | 50 |
| Part 1: Placebo + 52 Weeks Prednisone Taper Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks. | 51 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part 1: Blinded Period | Adverse Event | 7 | 3 | 2 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Blinded Period | Lack of Efficacy | 1 | 3 | 2 | 2 | 0 | 0 | 0 | 0 |
| Part 1: Blinded Period | Non-Compliance | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Blinded Period | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 1: Blinded Period | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 1: Blinded Period | Withdrawal by Subject | 6 | 2 | 2 | 1 | 0 | 0 | 0 | 0 |
| Part 2: Open-label Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 2 |
| Part 2: Open-label Period | Death | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Part 2: Open-label Period | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 2: Open-label Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2: Open-label Period | Physician Decision | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Part 2: Open-label Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 | 3 | 2 |
Baseline characteristics
| Characteristic | Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Part 1: Placebo + 26 Weeks Prednisone Taper | Part 1: Placebo + 52 Weeks Prednisone Taper | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.5 years STANDARD_DEVIATION 8.5 | 69.4 years STANDARD_DEVIATION 8.29 | 69.3 years STANDARD_DEVIATION 8.14 | 67.8 years STANDARD_DEVIATION 7.7 | 69.1 years STANDARD_DEVIATION 8.21 |
| Sex: Female, Male Female | 78 Participants | 34 Participants | 38 Participants | 37 Participants | 187 Participants |
| Sex: Female, Male Male | 22 Participants | 15 Participants | 12 Participants | 14 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 87 / 100 | 44 / 49 | 47 / 50 | 44 / 51 | 33 / 40 | 50 / 58 | 44 / 50 | 61 / 67 |
| serious Total, serious adverse events | 15 / 100 | 7 / 49 | 11 / 50 | 13 / 51 | 7 / 40 | 11 / 58 | 18 / 50 | 23 / 67 |
Outcome results
Primary
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper)
Remission was defined as the absence of flare and normalization of the C-reactive protein (CRP) (less than \[\<\] 1 milligram per deciliter \[mg/dL\]). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) attributable to GCA. A single CRP elevation (\>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (\>/=1 mg/dL) at the next study visit.
Time frame: Week 52
Population: Intent-to-treat (ITT) population included all participants randomized into the study who received at least one administration of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper) | 56.0 percentage of participants |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper) | 53.1 percentage of participants |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper) | 14.0 percentage of participants |
Comparison: The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (less than or equal to \[\</=\] 30 mg/day, greater than \[\>\] 30 mg/day).p-value: <0.000199.5% CI: [18, 66]Cochran-Mantel-Haenszel
Comparison: The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).p-value: <0.000199.5% CI: [12.46, 65.66]Cochran-Mantel-Haenszel
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab
AUCtau is the model-predicted area under the tocilizumab serum concentration versus time curve from time zero to the end of dosing interval. AUCtau is measured in microgram\*day per milliliter (mcg\*day/mL).
Time frame: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Population: Pharmacokinetics (PK)-evaluable population included all participants who received at least one tocilizumab injection and had at least one PK sample with detectable results taken at any time during the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab | 499.2 mcg*day/mL | Standard Deviation 210.4 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab | 227.2 mcg*day/mL | Standard Deviation 165.4 |
Secondary
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52
Participants assessed their current disease activity on a 0-100 millimeter (mm) VAS, where 0 mm = no disease activity and 100 mm = maximum disease activity. A negative change from baseline indicates improvement.
Time frame: Baseline, Week 52
Population: ITT population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Baseline (n=100,49,49,51) | 43.61 mm | Standard Deviation 25.66 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Change at Week 52 (n=60,26,11,18) | -19.68 mm | Standard Deviation 33.64 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Change at Week 52 (n=60,26,11,18) | -22.69 mm | Standard Deviation 22.41 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Baseline (n=100,49,49,51) | 46.65 mm | Standard Deviation 25.6 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Baseline (n=100,49,49,51) | 35.73 mm | Standard Deviation 28.15 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Change at Week 52 (n=60,26,11,18) | -8.45 mm | Standard Deviation 24.81 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Baseline (n=100,49,49,51) | 47.78 mm | Standard Deviation 27.8 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52 | Change at Week 52 (n=60,26,11,18) | -10.00 mm | Standard Deviation 35.12 |
Comparison: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.031299% CI: [-34.3, 3.1]Repeated measures model
Comparison: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.047699% CI: [-27.2, 3.6]Repeated measures model
Comparison: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.005999% CI: [-42.4, -1.4]Repeated measures model
Comparison: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.008199% CI: [-35.8, -0.5]Repeated measures model
Secondary
Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52
The SF-36 is a standardized questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical Component Score (PCS) and Mental Component Score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). A positive change from baseline indicates improvement. No imputation was used for missing data. Data was set to missing for participants who received escape therapy.
Time frame: Baseline, Week 52
Population: ITT population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | PCS: Baseline (n=97,49,48,49) | 43.10 units on a scale | Standard Deviation 9.43 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | PCS: Change at Week 52 (n=59,26,9,18) | 5.37 units on a scale | Standard Deviation 7.38 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | MCS: Baseline (n=97,49,48,49) | 42.77 units on a scale | Standard Deviation 12.43 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | MCS: Change at Week 52 (n=59,26,9,18) | 8.21 units on a scale | Standard Deviation 10.35 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | PCS: Change at Week 52 (n=59,26,9,18) | 2.71 units on a scale | Standard Deviation 8.86 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | MCS: Baseline (n=97,49,48,49) | 47.67 units on a scale | Standard Deviation 12.59 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | MCS: Change at Week 52 (n=59,26,9,18) | 1.98 units on a scale | Standard Deviation 7.17 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | PCS: Baseline (n=97,49,48,49) | 40.62 units on a scale | Standard Deviation 8 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | MCS: Baseline (n=97,49,48,49) | 42.73 units on a scale | Standard Deviation 12.13 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | PCS: Change at Week 52 (n=59,26,9,18) | 2.08 units on a scale | Standard Deviation 12.11 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | MCS: Change at Week 52 (n=59,26,9,18) | 4.99 units on a scale | Standard Deviation 7.54 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | PCS: Baseline (n=97,49,48,49) | 42.65 units on a scale | Standard Deviation 10.87 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | MCS: Change at Week 52 (n=59,26,9,18) | 2.60 units on a scale | Standard Deviation 10.56 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | PCS: Change at Week 52 (n=59,26,9,18) | -2.80 units on a scale | Standard Deviation 6.98 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | PCS: Baseline (n=97,49,48,49) | 41.12 units on a scale | Standard Deviation 9.97 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52 | MCS: Baseline (n=97,49,48,49) | 40.45 units on a scale | Standard Deviation 13.73 |
Comparison: MCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.806799% CI: [-5.86, 7.07]Repeated measures model
Comparison: MCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.025299% CI: [-0.69, 9.56]Repeated measures model
Comparison: MCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.837499% CI: [-7.64, 6.53]Repeated measures model
Comparison: MCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.146899% CI: [-2.59, 9.14]Repeated measures model
Comparison: PCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.05799% CI: [-1.58, 10.34]Repeated measures model
Comparison: PCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.002499% CI: [0.86, 10.32]Repeated measures model
Comparison: PCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.221899% CI: [-3.43, 9.51]Repeated measures model
Comparison: PCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (\<=30mg/day, \>30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.p-value: 0.041299% CI: [-1.14, 9.64]Repeated measures model
Secondary
C-Reactive Protein (CRP) Level
The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time frame: Baseline and Week 52
Population: Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | C-Reactive Protein (CRP) Level | Baseline (n=100,49,50,51) | 3.67 milligrams per liter (mg/L) | Inter-Quartile Range 61.98 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | C-Reactive Protein (CRP) Level | Week 52 (n=76,35,35,33) | 0.30 milligrams per liter (mg/L) | — |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | C-Reactive Protein (CRP) Level | Baseline (n=100,49,50,51) | 4.52 milligrams per liter (mg/L) | Inter-Quartile Range 63.51 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | C-Reactive Protein (CRP) Level | Week 52 (n=76,35,35,33) | 0.33 milligrams per liter (mg/L) | — |
| Part 1: Placebo + 26 Weeks Prednisone Taper | C-Reactive Protein (CRP) Level | Baseline (n=100,49,50,51) | 3.64 milligrams per liter (mg/L) | Inter-Quartile Range 11.32 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | C-Reactive Protein (CRP) Level | Week 52 (n=76,35,35,33) | 4.90 milligrams per liter (mg/L) | — |
| Part 1: Placebo + 52 Weeks Prednisone Taper | C-Reactive Protein (CRP) Level | Baseline (n=100,49,50,51) | 3.56 milligrams per liter (mg/L) | Inter-Quartile Range 10.84 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | C-Reactive Protein (CRP) Level | Week 52 (n=76,35,35,33) | 8.12 milligrams per liter (mg/L) | — |
Secondary
Erythrocyte Sedimentation Rate (ESR)
ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.
Time frame: Baseline and Week 52
Population: Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Erythrocyte Sedimentation Rate (ESR) | Baseline (n=99,49,50,51) | 19.00 mm/hr | Inter-Quartile Range 61.98 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Erythrocyte Sedimentation Rate (ESR) | Week 52 (n=76,35,35,33) | 3.00 mm/hr | — |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Erythrocyte Sedimentation Rate (ESR) | Week 52 (n=76,35,35,33) | 5.00 mm/hr | — |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Erythrocyte Sedimentation Rate (ESR) | Baseline (n=99,49,50,51) | 15.00 mm/hr | Inter-Quartile Range 63.51 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Erythrocyte Sedimentation Rate (ESR) | Baseline (n=99,49,50,51) | 23.00 mm/hr | Inter-Quartile Range 11.32 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Erythrocyte Sedimentation Rate (ESR) | Week 52 (n=76,35,35,33) | 20.00 mm/hr | — |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Erythrocyte Sedimentation Rate (ESR) | Baseline (n=99,49,50,51) | 20.00 mm/hr | Inter-Quartile Range 10.84 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Erythrocyte Sedimentation Rate (ESR) | Week 52 (n=76,35,35,33) | 24.00 mm/hr | — |
Secondary
Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab
Cmax,ss is maximum model-predicted serum steady state concentration of tocilizumab measured in micrograms per milliliter (mcg/mL).
Time frame: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Population: PK-evaluable population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab | 73 mcg/mL | Standard Deviation 30.4 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab | 19.3 mcg/mL | Standard Deviation 12.8 |
Secondary
Minimum Observed Serum Concentration (Ctrough) of Tocilizumab
Ctrough is minimum observed serum concentration of tocilizumab measured in mcg/mL.
Time frame: Predose (Hour 0) at Baseline and Week 52
Population: PK-evaluable population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Minimum Observed Serum Concentration (Ctrough) of Tocilizumab | Baseline (n= 99, 48) | 0.07 mcg/mL | Standard Deviation 0.72 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Minimum Observed Serum Concentration (Ctrough) of Tocilizumab | Week 52 (n= 72, 33) | 67.93 mcg/mL | Standard Deviation 34.4 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Minimum Observed Serum Concentration (Ctrough) of Tocilizumab | Baseline (n= 99, 48) | 0.00 mcg/mL | Standard Deviation 0.02 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Minimum Observed Serum Concentration (Ctrough) of Tocilizumab | Week 52 (n= 72, 33) | 12.22 mcg/mL | Standard Deviation 10.02 |
Secondary
Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab
Cmin,ss is minimum model-predicted serum steady state concentration of tocilizumab measured in mcg/mL.
Time frame: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Population: PK-evaluable population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab | 68.1 mcg/mL | Standard Deviation 29.5 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab | 11.1 mcg/mL | Standard Deviation 10.3 |
Secondary
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper)
Remission was defined as the absence of flare and normalization of the CRP (\<1 mg/dL). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR \>/=30 mm/hr attributable to GCA. A single CRP elevation (\>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (\>/=1 mg/dL) at the next study visit.
Time frame: Week 52
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper) | 56.0 percentage of participants |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper) | 53.1 percentage of participants |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper) | 17.6 percentage of participants |
Comparison: The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).99.5% CI: [17.89, 58.81]
Comparison: The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).p-value: 0.0002Cochran-Mantel-Haenszel
Comparison: The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).99.5% CI: [10.41, 60.41]
Secondary
Percentage of Participants With Anti-Tocilizumab Antibodies
All samples were tested by screening assay, and those samples that were positive were further analyzed by a confirmation assay to confirm specificity. Percentage of participants who has a positive confirmation assay result any time after the initial drug administration with a negative confirmation assay result at baseline was reported.
Time frame: Baseline up to Week 52
Population: Safety population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Percentage of Participants With Anti-Tocilizumab Antibodies | 1.1 percentage of participants |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Percentage of Participants With Anti-Tocilizumab Antibodies | 6.5 percentage of participants |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Percentage of Participants With Anti-Tocilizumab Antibodies | 2.0 percentage of participants |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Percentage of Participants With Anti-Tocilizumab Antibodies | 2.1 percentage of participants |
Secondary
Serum Interleukin-6 (IL-6) Level
Time frame: Baseline and Week 52
Population: Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Serum Interleukin-6 (IL-6) Level | Baseline (n=91,44,50,47) | 8.79 picograms per milliliter (pg/mL) | Standard Deviation 10.01 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Serum Interleukin-6 (IL-6) Level | Week 52 (n=69,32,28,30) | 65.99 picograms per milliliter (pg/mL) | Standard Deviation 84.92 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Serum Interleukin-6 (IL-6) Level | Week 52 (n=69,32,28,30) | 52.70 picograms per milliliter (pg/mL) | Standard Deviation 33.1 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Serum Interleukin-6 (IL-6) Level | Baseline (n=91,44,50,47) | 16.29 picograms per milliliter (pg/mL) | Standard Deviation 31.23 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Serum Interleukin-6 (IL-6) Level | Baseline (n=91,44,50,47) | 12.73 picograms per milliliter (pg/mL) | Standard Deviation 18.04 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Serum Interleukin-6 (IL-6) Level | Week 52 (n=69,32,28,30) | 35.96 picograms per milliliter (pg/mL) | Standard Deviation 149.65 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Serum Interleukin-6 (IL-6) Level | Baseline (n=91,44,50,47) | 8.31 picograms per milliliter (pg/mL) | Standard Deviation 9.47 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Serum Interleukin-6 (IL-6) Level | Week 52 (n=69,32,28,30) | 10.85 picograms per milliliter (pg/mL) | Standard Deviation 15.17 |
Secondary
Serum Soluble IL-6 Receptor (sIL-6R) Level
Time frame: Baseline and Week 52
Population: Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Serum Soluble IL-6 Receptor (sIL-6R) Level | Baseline (n=99,48,50,50) | 51.34 nanograms per milliliter (ng/mL) | Standard Deviation 61.98 |
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Serum Soluble IL-6 Receptor (sIL-6R) Level | Week 52 (n=73,33,33,31) | 600.53 nanograms per milliliter (ng/mL) | Standard Deviation 217.52 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Serum Soluble IL-6 Receptor (sIL-6R) Level | Week 52 (n=73,33,33,31) | 464.30 nanograms per milliliter (ng/mL) | Standard Deviation 153.64 |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Serum Soluble IL-6 Receptor (sIL-6R) Level | Baseline (n=99,48,50,50) | 50.82 nanograms per milliliter (ng/mL) | Standard Deviation 63.51 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Serum Soluble IL-6 Receptor (sIL-6R) Level | Baseline (n=99,48,50,50) | 42.07 nanograms per milliliter (ng/mL) | Standard Deviation 11.32 |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Serum Soluble IL-6 Receptor (sIL-6R) Level | Week 52 (n=73,33,33,31) | 76.44 nanograms per milliliter (ng/mL) | Standard Deviation 149.2 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Serum Soluble IL-6 Receptor (sIL-6R) Level | Baseline (n=99,48,50,50) | 40.37 nanograms per milliliter (ng/mL) | Standard Deviation 10.84 |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Serum Soluble IL-6 Receptor (sIL-6R) Level | Week 52 (n=73,33,33,31) | 64.80 nanograms per milliliter (ng/mL) | Standard Deviation 105.13 |
Secondary
Time to First GCA Disease Flare
Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR \>/=30 mm/hr attributable to GCA. Participants who withdrew from the study prior to Week 52 were censored from the time of withdrawal.
Time frame: Up to 52 weeks
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Time to First GCA Disease Flare | NA days |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Time to First GCA Disease Flare | NA days |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Time to First GCA Disease Flare | 165.0 days |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Time to First GCA Disease Flare | 295.0 days |
Comparison: The treatment groups were compared using a Cox proportional hazards model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).p-value: <0.000199% CI: [0.11, 0.46]Cox proportional hazards model
Comparison: The treatment groups were compared using a Cox proportional hazards model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).p-value: 0.001199% CI: [0.18, 0.82]Cox proportional hazards model
Comparison: The treatment groups were compared using a Cox proportional hazards model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).p-value: 0.000199% CI: [0.12, 0.66]Cox proportional hazards model
Comparison: The treatment groups were compared using a Cox proportional hazards model adjusted for the stratification factor of starting prednisone dose (\</=30 mg/day, \>30 mg/day).p-value: 0.031699% CI: [0.2, 1.16]Cox proportional hazards model
Secondary
Total Cumulative Prednisone Dose
The median total cumulative prednisone dose over the 52 weeks for each treatment group and the corresponding 95% confidence intervals are presented.
Time frame: Up to 52 weeks
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper | Total Cumulative Prednisone Dose | 1862.00 milligrams (mg) |
| Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper | Total Cumulative Prednisone Dose | 1862.00 milligrams (mg) |
| Part 1: Placebo + 26 Weeks Prednisone Taper | Total Cumulative Prednisone Dose | 3296.00 milligrams (mg) |
| Part 1: Placebo + 52 Weeks Prednisone Taper | Total Cumulative Prednisone Dose | 3817.50 milligrams (mg) |
Comparison: The treatment groups were compared using a Van Elteren's test stratified by starting prednisone dose (\<=30 mg/day, \> 30 mg/day).p-value: <0.0001Van Elteren's test
Comparison: The treatment groups were compared using a Van Elteren's test stratified by starting prednisone dose (\<=30 mg/day, \> 30 mg/day).p-value: <0.0001Van Elteren's test
Comparison: The treatment groups were compared using a Van Elteren's test stratified by starting prednisone dose (\<=30mg/day, \>30mg/day).p-value: 0.0003Van Elteren's test
Comparison: The treatment groups were compared using a Van Elteren's test stratified by starting prednisone dose (\<=30 mg/day, \> 30 mg/day).p-value: <0.0001Van Elteren's test