Giant Cell Arteritis
Conditions
Keywords
GCA, Tocilizumab, Prednisone
Brief summary
This is an open-label pilot study of tocilizumab (TCZ) 162 mg weekly administered subcutaneously for 52 weeks in combination with 8 weeks of oral prednisone.
Detailed description
This is a single center, open label study that will assess the efficacy and safety of 52 weeks of tocilizumab (TCZ) in combination with 8-weeks of prednisone in 30 patients with active giant cell arteritis (GCA). Active disease is defined as signs and/or symptoms of GCA plus increased inflammatory markers (e.g., erythrosedimentation rate \[ESR\] and/or C-reactive protein \[CRP\]). The study will enroll subjects with new onset and with relapsing/refractory GCA, and consist of a screening phase (up to 6 weeks), a treatment phase (52 weeks) and a safety follow up phase (4 weeks). The primary endpoint of the study, sustained remission, will be assessed at week 52. The definition of sustained remission contains 3 elements: 1. Absence of clinical signs and symptoms of active GCA along with the normalization of the ESR (\< 40 mm/hour) and CRP (\< 10 mg/L). 2. Completion of the pre-specified prednisone taper protocol 3. Absence of disease flare (relapse) since the induction of remission by week 8. Disease flare is defined as the re-appearance of unequivocal signs or symptoms of active GCA (with or without elevation of ESR and/or CRP) or the elevation of the ESR and/or CRP that is thought to be due to active GCA and that requires escape therapy.
Interventions
DRUGTocilizumab
Tocilizumab is an interleukin-6 (IL-6) receptor inhibitor
DRUGPrednisone
Prednisone is an anti-inflammatory medication
Sponsors
Roche-Genentech
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability and willingness to provide written informed consent and to comply with the study protocol 2. Diagnosis of GCA classified per the following criteria: • Age 50 years or older AND at least one of the following: * Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp tenderness, temporal artery tenderness or decreased pulsation, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication) * Symptoms of polymyalgia rheumatica (PMR), defined as shoulder and / or hip girdle pain associated with inflammatory morning stiffness AND at least one of the following: * Cranial artery biopsy revealing features of GCA (e.g., mononuclear cell infiltration or granulomatous inflammation). * Evidence of large-vessel vasculitis by angiography or cross-sectional imaging study such as Image result for magnetic resonance angiogram (MRA), Computed tomography angiography (CTA) , or Image result for positron emission tomography (PET) and computed tomography (CT) (PET-CT) * Ultrasound demonstration of features of GCA in a cranial artery. 3. New-onset or relapsing/refractory active disease defined as follows: * New onset: diagnosis of GCA within 6 weeks of baseline visit * Relapsing/refractory: diagnosis of GCA \> 6 weeks before baseline visit AND • Active GCA within 6 weeks of baseline visit defined as the presence of clinical signs and symptoms \[cranial or PMR\] and erythrocyte sedimentation rate (ESR) ≥ 30 mm/hour or C-reactive protein (CRP) ≥ 10 mg/L)
Exclusion criteria
1. General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Remission | 52 weeks | Number and percentage of patients in sustained remission by week 52. Sustained remission was defined as the absence of disease flare between baseline and week 52. Flare was defined as the re-appearance of clinical manifestations of GCA with or without elevation of the inflammatory makers erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Flares | 52 Weeks | Total number of disease flares by week 52. Flare was defined as the re-appearance of clinical manifestations of GCA with or without elevation of the inflammatory makers erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) |
| Cumulative Prednisone Dose | 52 Weeks | Cumulative prednisone dose (mg) by week 52 |
| Adverse Events | 52 weeks | Number and percentage of participants with at least one adverse event by week 52 |
| Serious Adverse Events | 52 weeks | Number and percentage of participants with at least one serious adverse event by week 52 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab and Prednisone 1. TCZ 162 mg administered by subcutaneous injection weekly for 52 weeks.
2. Prednisone taper over 8 weeks with a starting dose between 20 and 60 mg.
Tocilizumab: Tocilizumab is an interleukin-6 (IL-6) receptor inhibitor
Prednisone: Prednisone is an anti-inflammatory medication | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Tocilizumab and Prednisone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 26 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 73.7 years STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 0 / 30 |
| serious Total, serious adverse events | 4 / 30 |
Outcome results
Primary
Sustained Remission
Number and percentage of patients in sustained remission by week 52. Sustained remission was defined as the absence of disease flare between baseline and week 52. Flare was defined as the re-appearance of clinical manifestations of GCA with or without elevation of the inflammatory makers erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tocilizumab and Prednisone | Sustained Remission | 23 Participants |
Secondary
Adverse Events
Number and percentage of participants with at least one adverse event by week 52
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tocilizumab and Prednisone | Adverse Events | 30 Participants |
Secondary
Cumulative Prednisone Dose
Cumulative prednisone dose (mg) by week 52
Time frame: 52 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab and Prednisone | Cumulative Prednisone Dose | 1187 mg | Standard Deviation 470.4 |
Secondary
Disease Flares
Total number of disease flares by week 52. Flare was defined as the re-appearance of clinical manifestations of GCA with or without elevation of the inflammatory makers erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)
Time frame: 52 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab and Prednisone | Disease Flares | 9 Total number of flares |
Secondary
Serious Adverse Events
Number and percentage of participants with at least one serious adverse event by week 52
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tocilizumab and Prednisone | Serious Adverse Events | 4 Participants |