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)

Giant Cell Arteritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03192969
• Other study ID #: IM101-604
• Secondary ID: 2016-002697-12
• Status: Withdrawn
• Phase: Phase 3
• First received: June 14, 2017
• Last updated: July 10, 2017
• Start date: July 15, 2017
• Est. completion date: November 23, 2021

Study information

• Verified date: July 2017
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 23, 2021
• Est. primary completion date: June 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Polymyalgia Rheumatica

Intervention

Drug:
• Abatacept
Abatacept subcutaneous injection, 125 mg/prefilled syringe (125 mg/mL)

Other:
• Placebo
Placebo for abatacept for subcutaneous injection in 1 mL pre-filled syringes

Drug:
• Glucocorticoid Treatment
Glucocorticoid taper (up to 52-week or 28-week of oral prednisone/prednisolone)

Locations

Country	Name	City	State
Australia	Local Institution	Auchenflower	Queensland
Australia	Local Institution	Malvern East	Victoria
Australia	Local Institution	Nedlands	Western Australia
Australia	Local Institution	Northmead	New South Wales
Australia	Local Institution	Victoria Park	Western Australia
Australia	Local Institution	Woodville South	South Australia
Austria	Local Institution	Graz
Austria	Local Institution	Stockerau
Belgium	Local Institution	Leuven
Belgium	Local Institution	Li?ge
Belgium	Local Institution	Yvoir
Bulgaria	Local Institution	Sofia	Sofia-grad
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Saskatoon	Saskatchewan
Canada	Local Institution	Trois-Rivieres	Quebec
Denmark	Local Institution	Aarhus C
Denmark	Local Institution	Esbjerg
Denmark	Local Institution	Glostrup
Denmark	Local Institution	Holstebro
Denmark	Local Institution	Odense C
Denmark	Local Institution	Silkeborg
Estonia	Local Institution	Tallinn
Estonia	Local Institution	Tallinn
Estonia	Local Institution	Tartu
France	Local Institution	Marseille
France	Local Institution	Nantes
France	Local Institution	Paris
France	Local Institution	Paris Cedex 14
France	Local Institution	Pau
France	Local Institution	Toulouse
Germany	Local Institution	Berlin
Germany	Local Institution	Berlin
Germany	Local Institution	Dresden
Germany	Local Institution	Freiburg im Breisgau
Germany	Local Institution	Hamburg
Germany	Local Institution	Hannover
Germany	Local Institution	Herne
Germany	Local Institution	Kirchheim
Germany	Local Institution	Rostock
Germany	Local Institution	Tubingen
Germany	Local Institution	W?rzburg
Greece	Local Institution	Athens
Greece	Local Institution	Larissa
Greece	Local Institution	Thessaloniki
Ireland	Local Institution	Dublin
Italy	Local Institution	Catania
Italy	Local Institution	Genova
Italy	Local Institution	Milano
Italy	Local Institution	Milano
Italy	Local Institution	Milano
Italy	Local Institution	Padova
Italy	Local Institution	Pavia
Italy	Local Institution	Prato
Italy	Local Institution	Torino
Netherlands	Local Institution	Almelo
Netherlands	Local Institution	Enschede
Netherlands	Local Institution	Groningen
Netherlands	Local Institution	Helmond
Netherlands	Local Institution	Rotterdam
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Krakow
Poland	Local Institution	Szczecin
Poland	Local Institution	Warszawa
Poland	Local Institution	Wroclaw
Romania	Local Institution	Cluj-Napoca
Romania	Local Institution	Sibiu
Serbia	Local Institution	Belgrade
Spain	Local Institution	Barcelona
Spain	Local Institution	Bilbao
Spain	Local Institution	L'Hospitalet de Llobregat
Spain	Local Institution	La Laguna
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Vitoria
Sweden	Local Institution	Stockholm
Sweden	Local Institution	Uppsala
Sweden	Local Institution	V?ster?s
Switzerland	Local Institution	Basel
Switzerland	Local Institution	Bern
Switzerland	Local Institution	Freiburg
Switzerland	Local Institution	St. Gallen
Switzerland	Local Institution	Z?rich
United Kingdom	Local Institution	London
United Kingdom	Local Institution	Newcastle upon Tyne	Tyne and Wear
United Kingdom	Local Institution	Westcliff-on-Sea	Essex
United States	Local Institution	Beaumont	Texas
United States	Local Institution	Charleston	South Carolina
United States	Local Institution	Cleveland	Ohio
United States	Local Institution	Dayton	Ohio
United States	Local Institution	Denver	Colorado
United States	Local Institution	Fullerton	California
United States	Local Institution	Iowa City	Iowa
United States	Local Institution	Kansas City	Kansas
United States	Local Institution	New York	New York
United States	Local Institution	Philadelphia	Pennsylvania
United States	Local Institution	Phoenix	Arizona
United States	Local Institution	Rochester	Minnesota
United States	Local Institution	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Denmark,  Estonia,  France,  Germany,  Greece,  Ireland,  Italy,  Netherlands,  Poland,  Romania,  Serbia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry Form