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)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase III Randomized, Placebo-Controlled, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Abatacept in Combination With Glucocorticoid Treatment Compared to Glucocorticoid Monotherapy in Adults With Giant Cell Arteritis

Conditions
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Giant Cell Arteritis

Intervention / Treatment
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* Drug: Abatacept
* Other: Placebo
* Drug: Glucocorticoid Treatment


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abatacept Combination Therapy<br>Abatacept subcutaneous injection (125 mg/mL prefilled syringe weekly) in combination with glucocorticoid therapy (up to 28-week taper of oral prednisone daily) | Drug: Abatacept<br>* Abatacept subcutaneous injection, 125 mg/prefilled syringe (125 mg/mL)<br>Drug: Glucocorticoid Treatment<br>* Glucocorticoid taper (up to 52-week or 28-week of oral prednisone/prednisolone)<br>|
| Placebo Comparator: Placebo Monotherapy- 28 Weeks<br>Glucocorticoid therapy (28-week taper of oral prednisone daily) in combination with placebo subcutaneous injection (1 mL pre-filled syringe weekly) | Other: Placebo<br>* Placebo for abatacept for subcutaneous injection in 1 mL pre-filled syringes<br>Drug: Glucocorticoid Treatment<br>* Glucocorticoid taper (up to 52-week or 28-week of oral prednisone/prednisolone)<br>|
| Placebo Comparator: Placebo Monotherapy- 52 Weeks<br>Glucocorticoid therapy (52 week taper of oral prednisone daily) in combination with subcutaneous placebo weekly | Other: Placebo<br>* Placebo for abatacept for subcutaneous injection in 1 mL pre-filled syringes<br>Drug: Glucocorticoid Treatment<br>* Glucocorticoid taper (up to 52-week or 28-week of oral prednisone/prednisolone)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients in sustained remission | 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. | 40 weeks (week 12 to week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician's Global Assessment of Disease Activity according to visual analog scale (VAS) | measured by assessment parameters | Up to 52 weeks | 
| Subject Assessment of Disease Activity according to visual analog scale (VAS) | measured by assessment parameters | Up to 52 weeks | 
| Short Form questionnaire-36 (SF-36) | Patient reported outcome assessment | Up to 52 weeks | 
| Time from Week 12 to first relapse after achieving remission | measured by investigator | 40 weeks (week 12 to week 52) | 
| Erythrocyte sedimentation rate (ESR) | Mean change from baseline. | 52 weeks | 
| C-reactive protein (CRP) | Mean change from baseline. | 52 weeks | 
| All adverse events and serious adverse events (AEs/SAEs) | measured by incidence of AEs and SAEs | 52 weeks | 
| Laboratory test abnormalities | measured by laboratory test parameters | 52 weeks | 
| Cmin (μg/mL): Trough level serum concentration of abatacept prior to the administration of the subcutaneous injection | measured by serum concentration | 104 weeks | 
| Positive abatacept response relative to baseline | 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. | 52 weeks | 
| Cumulative glucocorticoid dose | measured as the total glucocorticoid dose used during the treatment period | 52 weeks | 
| EuroQOL 5 Dimensions (EQ-5D-3L) | Patient reported outcome assessment | Up to 52 weeks | 
| Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 8a | Patient reported outcome assessment | Up to 52 weeks | 
| Resource Utilization | Assessed by the number of hospitalizations | Up to 52 weeks |