A Study to Evaluate Efficacy and Safety of Subcutaneous Abatacept With Steroid Treatment Compared to Steroid Treatment Alone in Adults With Giant Cell Arteritis (GCA)
- Conditions
- Giant Cell Arteritis
- Interventions
- Registration Number
- NCT03192969
- Lead Sponsor
- Bristol-Myers Squibb
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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/exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Monotherapy- 52 Weeks Placebo Glucocorticoid therapy (52 week taper of oral prednisone daily) in combination with subcutaneous placebo weekly Abatacept Combination Therapy Glucocorticoid Treatment Abatacept subcutaneous injection (125 mg/mL prefilled syringe weekly) in combination with glucocorticoid therapy (up to 28-week taper of oral prednisone daily) Placebo Monotherapy- 28 Weeks Placebo Glucocorticoid therapy (28-week taper of oral prednisone daily) in combination with placebo subcutaneous injection (1 mL pre-filled syringe weekly) Placebo Monotherapy- 52 Weeks Glucocorticoid Treatment Glucocorticoid therapy (52 week taper of oral prednisone daily) in combination with subcutaneous placebo weekly Placebo Monotherapy- 28 Weeks Glucocorticoid Treatment Glucocorticoid therapy (28-week taper of oral prednisone daily) in combination with placebo subcutaneous injection (1 mL pre-filled syringe weekly) Abatacept Combination Therapy Abatacept Abatacept subcutaneous injection (125 mg/mL prefilled syringe weekly) in combination with glucocorticoid therapy (up to 28-week taper of oral prednisone daily)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Erythrocyte sedimentation rate (ESR) 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
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
Time from Week 12 to first relapse after achieving remission 40 weeks (week 12 to week 52) measured by investigator
C-reactive protein (CRP) 52 weeks Mean change from baseline.
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
Resource Utilization Up to 52 weeks Assessed by the number of hospitalizations
Trial Locations
- Locations (1)
Local Institution
🇬🇧London, United Kingdom