Giant Cell Arteritis
Conditions
Brief summary
To investigate the safety and efficacy of abatacept with steroid treatment in comparison to steroid treatment alone in up to a 28 week taper of steroid treatment to sustain remission of Giant Cell Arteritis in adults.
Interventions
DRUGAbatacept
Abatacept subcutaneous injection, 125 mg/prefilled syringe (125 mg/mL)
OTHERPlacebo
Placebo for abatacept for subcutaneous injection in 1 mL pre-filled syringes
Glucocorticoid taper (up to 52-week or 28-week of oral prednisone/prednisolone)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * New headache (new onset or new type of localized pain in the head) * Elevated ESR (≥ 50 mm/h by the Westergren method) or CRP ≥ 1 mg/dL * Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries) * Temporal artery biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells * Large vessel biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells or characteristic changes of large vessel stenosis or aneurysm secondary to GCA as seen by arteriography (Magnetic Resonance Imaging/ Magnetic Resonance Angiography), ultrasound (eg, halo sign on color duplex sonography), or CT scan * Patients must be treated with prednisone or prednisolone of 20-60 mg/day (prednisone equivalent) and be on a dose between 20-60 mg/day for at least 2 weeks prior to enrollment into the study
Exclusion criteria
* Rheumatic disease other than GCA such as Takayasu's Arteritis, granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, systemic lupus erythematosus * Patients with unilateral blindness (partial or complete) or who have unstable or recurrent visual symptoms attributable to GCA within 4 weeks of randomization * Patients with a history of dissection of aorta * Patients with a history of myocardial infarction, stroke or transient ischemic attack attributable to GCA within the 3 months of screening * Patients who have been treated with intravenous (pulse) doses of glucocorticoids defined as methylprednisolone \> 1000 mg/day if given within 6 weeks of randomization * Patients who will require oral or IV glucocorticoid treatment during the trial for conditions other than GCA * Patients at risk of tuberculosis Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients in sustained remission | 40 weeks (week 12 to week 52) | Assessment based on 2-sided stratified Cochran-Mantel-Haenszel (CMH) chi-square test, stratified by baseline glucocorticoid dose group (20-\< 30, 30-\< 40, 40-\< 50 and 50-60 mg/day) and GCA diagnosis (New vs Relapse) at a 5% significance level. Remission is defined as the absence of clinical signs and symptoms of active disease attributable to GCA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Global Assessment of Disease Activity according to visual analog scale (VAS) | Up to 52 weeks | measured by assessment parameters |
| Subject Assessment of Disease Activity according to visual analog scale (VAS) | Up to 52 weeks | measured by assessment parameters |
| Short Form questionnaire-36 (SF-36) | Up to 52 weeks | Patient reported outcome assessment |
| Time from Week 12 to first relapse after achieving remission | 40 weeks (week 12 to week 52) | measured by investigator |
| Erythrocyte sedimentation rate (ESR) | 52 weeks | Mean change from baseline. |
| C-reactive protein (CRP) | 52 weeks | Mean change from baseline. |
| All adverse events and serious adverse events (AEs/SAEs) | 52 weeks | measured by incidence of AEs and SAEs |
| Laboratory test abnormalities | 52 weeks | measured by laboratory test parameters |
| Cmin (μg/mL): Trough level serum concentration of abatacept prior to the administration of the subcutaneous injection | 104 weeks | measured by serum concentration |
| Positive abatacept response relative to baseline | 52 weeks | A validated, sensitive, electrochemiluminescence assay (ECL) method will be used to analyze the presence of anti-abatacept antibodies in serum. Samples that are confirmed positive for antibodies specific to the CTLA4 region of abatacept will be further analyzed with a validated, in vitro, cell-based bioassay to determine whether the sera contained abatacept neutralizing activity. |
| Cumulative glucocorticoid dose | 52 weeks | measured as the total glucocorticoid dose used during the treatment period |
| EuroQOL 5 Dimensions (EQ-5D-3L) | Up to 52 weeks | Patient reported outcome assessment |
| Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 8a | Up to 52 weeks | Patient reported outcome assessment |
| Resource Utilization | Up to 52 weeks | Assessed by the number of hospitalizations |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Denmark, Estonia, France, Germany, Greece, Ireland, Italy, Netherlands, Poland, Romania, Serbia, Spain, Sweden, Switzerland, United Kingdom, United States
Outcome results
None listed