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)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Giant Cell Arteritis
• Intervention / Treatment: Drug: Abatacept; Drug: Glucocorticoid Treatment; Other: Placebo

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Northmead, New South Wales, Australia, 2152
      • Local Institution
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Local Institution
  • South Australia
    • Woodville South, South Australia, Australia, 5001
      • Local Institution
  • Victoria
    • Malvern East, Victoria, Australia, 3145
      • Local Institution
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution
    • Victoria Park, Western Australia, Australia, 6100
      • Local Institution
• Austria
  • Graz, Austria, 8036
    • Local Institution
  • Stockerau, Austria, 2000
    • Local Institution
• Belgium
  • Leuven, Belgium, 3000
    • Local Institution
  • Li?ge, Belgium, 4000
    • Local Institution
  • Yvoir, Belgium, 5530
    • Local Institution
• Bulgaria
  • Sofia-grad
    • Sofia, Sofia-grad, Bulgaria, 1606
      • Local Institution
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Local Institution
  • Quebec
    • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
      • Local Institution
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
      • Local Institution
• Denmark
  • Aarhus C, Denmark, 8000
    • Local Institution
  • Esbjerg, Denmark, 6700
    • Local Institution
  • Glostrup, Denmark, 2600
    • Local Institution
  • Holstebro, Denmark, DK-7500
    • Local Institution
  • Odense C, Denmark, 5000
    • Local Institution
  • Silkeborg, Denmark, DK-8600
    • Local Institution
• Estonia
  • Tallinn, Estonia, 11312
    • Local Institution
  • Tallinn, Estonia, EE-13419
    • Local Institution
  • Tartu, Estonia, 50107
    • Local Institution
• France
  • Marseille, France, 13385
    • Local Institution
  • Nantes, France, 44093
    • Local Institution
  • Paris, France, 75018
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Pau, France, 64000
    • Local Institution
  • Toulouse, France, 31059
    • Local Institution
• Germany
  • Berlin, Germany, 14050
    • Local Institution
  • Berlin, Germany, 13125
    • Local Institution
  • Dresden, Germany, 01277
    • Local Institution
  • Freiburg im Breisgau, Germany, 79095
    • Local Institution
  • Hamburg, Germany, 22767
    • Local Institution
  • Hannover, Germany, D30625
    • Local Institution
  • Herne, Germany, 44652
    • Local Institution
  • Kirchheim, Germany, 73230
    • Local Institution
  • Rostock, Germany, 18059
    • Local Institution
  • Tubingen, Germany, 72076
    • Local Institution
  • W?rzburg, Germany, 97080
    • Local Institution
• Greece
  • Athens, Greece, 11527
    • Local Institution
  • Larissa, Greece, 41110
    • Local Institution
  • Thessaloniki, Greece, 56429
    • Local Institution
• Ireland
  • Dublin, Ireland
    • Local Institution
• Italy
  • Catania, Italy, 95124
    • Local Institution
  • Genova, Italy, 16132
    • Local Institution
  • Milano, Italy, 20132
    • Local Institution
  • Milano, Italy, 20121
    • Local Institution
  • Milano, Italy, 20157
    • Local Institution
  • Padova, Italy, 35128
    • Local Institution
  • Pavia, Italy, 27100
    • Local Institution
  • Prato, Italy, 51900
    • Local Institution
  • Torino, Italy, 10126
    • Local Institution
• Netherlands
  • Almelo, Netherlands, 7609 PP
    • Local Institution
  • Enschede, Netherlands, 7513 ER
    • Local Institution
  • Groningen, Netherlands, 9713 GZ
    • Local Institution
  • Helmond, Netherlands, 5707 HA
    • Local Institution
  • Rotterdam, Netherlands, 3059XN
    • Local Institution
• Poland
  • Bydgoszcz, Poland, 85-168
    • Local Institution
  • Krakow, Poland, 31-501
    • Local Institution
  • Szczecin, Poland, 71-252
    • Local Institution
  • Warszawa, Poland, 02-637
    • Local Institution
  • Wroclaw, Poland, 52-416
    • Local Institution
• Romania
  • Cluj-Napoca, Romania, 400006
    • Local Institution
  • Sibiu, Romania, 550245
    • Local Institution
• Serbia
  • Belgrade, Serbia, 11000
    • Local Institution
• Spain
  • Barcelona, Spain, 08025
    • Local Institution
  • Bilbao, Spain, 48013
    • Local Institution
  • L'Hospitalet de Llobregat, Spain, 08907
    • Local Institution
  • La Laguna, Spain, 38320
    • Local Institution
  • Madrid, Spain, 28034
    • Local Institution
  • Madrid, Spain, 28007
    • Local Institution
  • Madrid, Spain, 28040
    • Local Institution
  • Vitoria, Spain, 01009
    • Local Institution
• Sweden
  • Stockholm, Sweden, SE-18288
    • Local Institution
  • Uppsala, Sweden, 755 92
    • Local Institution
  • V?ster?s, Sweden, 72189
    • Local Institution
• Switzerland
  • Basel, Switzerland, 4031
    • Local Institution
  • Bern, Switzerland, 3010
    • Local Institution
  • Freiburg, Switzerland, 1708
    • Local Institution
  • St. Gallen, Switzerland, 9007
    • Local Institution
  • Z?rich, Switzerland, 8091
    • Local Institution
• United Kingdom
  • London, United Kingdom, E1 1BB
    • Local Institution
  • Essex
    • Westcliff-on-Sea, Essex, United Kingdom, SS0 0RY
      • Local Institution
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
      • Local Institution
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Local Institution
  • California
    • Fullerton, California, United States, 92835
      • Local Institution
    • West Hollywood, California, United States, 90048
      • Local Institution
  • Colorado
    • Denver, Colorado, United States, 80230
      • Local Institution
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Local Institution
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Local Institution
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Local Institution
  • New York
    • New York, New York, United States, 10021
      • Local Institution
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Local Institution
    • Dayton, Ohio, United States, 45417
      • Local Institution
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Local Institution
  • Texas
    • Beaumont, Texas, United States, 77702
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Anticipated): July 15, 2017
• Primary Completion (Anticipated): June 7, 2020
• Study Completion (Anticipated): November 23, 2021

Study Registration Dates

• First Submitted: June 14, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (Actual): June 20, 2017

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: July 10, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Muscular Diseases; Vasculitis; Skin Diseases, Vascular; Vasculitis, Central Nervous System; Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Immune Checkpoint Inhibitors; Abatacept; Glucocorticoids
• Other Study ID Numbers: IM101-604; 2016-002697-12 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No