A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis

Giant Cell Arteritis (GCA) Clinical Trial

— SELECT-GCA  

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Giant Cell Arteritis: SELECT-GCA

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03725202
• Other study ID #: M16-852
• Secondary ID: 2023-505476-29-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 24, 2019
• Est. completion date: March 3, 2025

Study information

• Verified date: February 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study consists of two periods. The objective of Period 1 is to evaluate the efficacy of upadacitinib in combination with a 26-week corticosteroid (CS) taper regimen compared to placebo in combination with a 52-week CS taper regimen, as measured by the proportion of participants in sustained remission at Week 52, and to assess the safety and tolerability of upadacitinib in participants with giant cell arteritis (GCA). The objective of period 2 is to evaluate the safety and efficacy of continuing versus withdrawing upadacitinib in maintaining remission in participants who achieved sustained remission in Period 1.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 429
• Est. completion date: March 3, 2025
• Est. primary completion date: February 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of giant cell arteritis (GCA) according to the following criteria:
• History of erythrocyte sedimentation rate (ESR) >= 50 mm/hour or high sensitivity C-reactive protein (hsCRP)/CRP >=1.0 mg/dL
• Presence of at least one of the following: Unequivocal cranial symptoms of GCA or Unequivocal symptoms of polymyalgia rheumatica (PMR)
• Presence of at least one of the following: temporal artery biopsy revealing features of GCA or evidence of large vessel vasculitis by angiography or cross-sectional imaging such as ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) or positron emission tomography (PET).
• Active GCA, either new onset or relapsing, within 8 weeks of Baseline.
• Participants must have received treatment with >=40 mg prednisone (or equivalent) at any time prior to Baseline and be receiving prednisone (or equivalent) >= 20 mg once daily (QD) at Baseline.
• Participants must have GCA that, in the opinion of the investigator, is clinically stable to allow the participant to safely initiate the protocol-defined corticosteroid (CS) taper regimen.
• Females must either be postmenopausal or permanently surgically sterile or, practicing at least 1 specified method of birth control through the study.

Exclusion Criteria:

• Prior exposure to any Janus Kinase (JAK) inhibitor.
• Treatment with an interleukin-6 (IL-6) inhibitor within 4 weeks of study start, or prior treatment with an IL-6 inhibitor and experienced a disease flare during treatment.
• Use of any of the following systemic immunosuppressant treatments within the specified

timeframe prior to study start:

• Anakinra within 1 week of study start.
• Methotrexate, hydroxychloroquine, cyclosporine, azathioprine, or mycophenolate within 4 weeks of study start.
• Oral corticosteroid (CS) for conditions other than GCA within 4 week of study start, or intravenous CS within 4 weeks of study start.
• Greater than or equal to 8 weeks for leflunomide if no elimination procedure was followed, or adhere to an elimination procedure.
• Cell-depleting agents or alkylating agents including cyclophosphamide within 6 months of study start.
• Current or past history of infection including herpes zoster or herpes simplex, human immunodeficiency virus (HIV), active Tuberculosis, active or chronic recurring infection, active hepatitis B or C.
• Female who is pregnant, breastfeeding, or considering pregnancy during the study.

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Giant Cell Arteritis (GCA)
• Polymyalgia Rheumatica

Intervention

Drug:
• Upadacitinib
It will be administered orally.
• Corticosteroid (CS)
It will be administered orally.

Other:
• Placebo
It will be administered orally.

Locations

Country	Name	City	State
Australia	Emeritus Research Sydney /ID# 201937	Botany	New South Wales
Australia	Emeritus Research /ID# 201938	Camberwell	Victoria
Australia	Fiona Stanley Hospital /ID# 201941	Murdoch	Western Australia
Australia	Prince of Wales Hospital /ID# 210995	Randwick	New South Wales
Australia	Griffith University /ID# 223829	Southport	Queensland
Australia	The Queen Elizabeth Hospital /ID# 201939	Woodville South	South Australia
Austria	Medizinische Universitaet Innsbruck /ID# 201786	Innsbruck	Tirol
Austria	Rheuma-Zentrum Wien-Oberlaa GmbH /ID# 201781	Vienna	Wien
Belgium	UZ Gent /ID# 202778	Gent	Oost-Vlaanderen
Belgium	CHU UCL Namur - site Godinne /ID# 224334	Godinne	Namur
Belgium	Universitair Ziekenhuis Leuven /ID# 202779	Leuven	Vlaams-Brabant
Canada	Duplicate_University of Alberta Hospital - Division of Hematology /ID# 208629	Edmonton	Alberta
Canada	St. Joseph's Healthcare /ID# 204160	Hamilton	Ontario
Canada	CISSSBSL -Hopital regional de Rimouski /ID# 224266	Rimouski	Quebec
Canada	Rheumatology Associates /ID# 201843	Saskatoon	Saskatchewan
Canada	Centre de Recherche Musculo-Squelettique /ID# 201224	Trois-rivières	Quebec
Czechia	Fakultni nemocnice Olomouc /ID# 202041	Olomouc
Czechia	Axon Clinical, s.r.o. /ID# 202468	Praha
Czechia	Medical Plus, s.r.o. /ID# 200865	Uherske Hradiste
Denmark	Aarhus University Hospital /ID# 171177	Aarhus C	Midtjylland
Denmark	Sydvestjysk Sygehus /ID# 200216	Esbjerg
France	Hopital de la Cavale Blanche /ID# 171549	Brest	Finistere
France	CHU de CAEN - Hopital de la Cote de Nacre /ID# 171539	Caen
France	CHRU Tours - Hopital Trousseau /ID# 245232	Chambray Les Tours
France	CHU Dijon /ID# 225277	Dijon	Cote-d Or
France	CHRU Lille - Hopital Claude Huriez /ID# 171543	Lille	Nord
France	HCL - Hopital de la Croix-Rousse /ID# 211184	Lyon	Rhone
France	Hopital Saint Joseph /ID# 171540	Marseille	Bouches-du-Rhone
France	CHU de Nantes, Hotel Dieu -HME /ID# 171544	Nantes	Pays-de-la-Loire
France	Hopital Pitie Salpetriere /ID# 171542	Paris
France	Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 171545	Paris CEDEX 14	Paris
France	CHU Toulouse - Hopital Purpan /ID# 171547	TOULOUSE Cedex 9	Haute-Garonne
Germany	Immanuel Krankenhaus Berlin /ID# 223855	Berlin-buch
Germany	Medizinische Versorgungszentren Burghausen Altoetting /ID# 208773	Burghausen
Germany	Medizinische Hochschule Hannover /ID# 200632	Hannover
Germany	Medius Klinik Kirchheim /ID# 200637	Kirchheim unter Teck	Baden-Wuerttemberg
Germany	Universitaetsklinikum Tuebingen /ID# 223854	Tubingen	Baden-Wuerttemberg
Germany	Universitaetsklinikum Wuerzburg /ID# 213340	Wuerzburg
Greece	General Hospital of Athens Gennimatas /ID# 210129	Athens	Attiki
Greece	General Hospital of Athens Ippokratio /ID# 202181	Athens	Attiki
Greece	424 General MILITARY Hospital /ID# 210973	Efkarpia (Thessalonikis)	Thessaloniki
Hungary	Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz /ID# 204018	Budapest
Hungary	Del-Budai Centrumkorhaz Szent Imre Egyetemi Oktatokorhaz /ID# 201838	Budapest
Hungary	Orszagos Reumatologiai es Fizioterapias Intezet /ID# 211454	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont /ID# 201526	Debrecen	Hajdu-Bihar
Israel	Bnai Zion Medical Center /ID# 240733	Haifa	H_efa
Israel	The Lady Davis Carmel Medical Center /ID# 240731	Haifa	H_efa
Israel	The Chaim Sheba Medical Center /ID# 241041	Ramat Gan	Tel-Aviv
Italy	Azienda Sanitaria dell'Alto Adige/Ospedale di Bolzano /ID# 200081	Bolzano
Italy	Azienda Ospedaliero-Universitaria di Modena /ID# 200079	Modena
Italy	Azienda Ospedaliera Universitaria Friuli Centrale/Presidio Ospedaliero Universit /ID# 200082	Udine
Japan	St.Luke's International Hospital /ID# 200170	Chuo-ku	Tokyo
Japan	St. Marianna University Hospital /ID# 218692	Kawasaki-shi	Kanagawa
Japan	Kagawa University Hospital /ID# 200171	Kita-gun	Kagawa
Japan	Japanese Red Cross Kumamoto Hospital /ID# 203507	Kumamoto-shi	Kumamoto
Japan	Japan Organization of Occupational Health and Safety Chubu Rosai Hospital /ID# 202946	Nagoya-shi	Aichi
Japan	Okayama University Hospital /ID# 203156	Okayama-shi	Okayama
Japan	Sakai City Medical Center /ID# 202643	Sakai-shi	Osaka
Japan	Tohoku University Hospital /ID# 200172	Sendai-shi	Miyagi
Japan	Duplicate_Jichi Medical University Hosp /ID# 200169	Shimotsuke-shi	Tochigi
Japan	Tomishiro Central Hospital /ID# 203897	Tomigusuku-shi	Okinawa
Netherlands	ZiekenhuisGroep Twente /ID# 200038	Almelo
Netherlands	Universitair Medisch Centrum Groningen /ID# 201715	Groningen
Netherlands	Zuyderland Medisch Centrum /ID# 224551	Heerlen	Limburg
Netherlands	Medisch Centrum Leeuwarden /ID# 201716	Leeuwarden
Netherlands	Radboud Universitair Medisch Centrum /ID# 212925	Nijmegen	Gelderland
Netherlands	Erasmus Medisch Centrum /ID# 201717	Rotterdam	Zuid-Holland
New Zealand	CGM Research Trust /ID# 224061	Christchurch Central
New Zealand	Optimal Clinical Trials Ltd /ID# 201946	Grafotn	Auckland
New Zealand	Waikato Hospital /ID# 201944	Hamilton	Waikato
New Zealand	Porter Rheumatology Ltd /ID# 223830	Nelson
New Zealand	Aotearoa Clinical Trials /ID# 201942	Papatoetoe	Auckland
New Zealand	Timaru Medical Specialists Ltd /ID# 201943	Timaru	Canterbury
Norway	Haukeland universitetssjukehus /ID# 201602	Bergen	Hordaland
Norway	Drammen Sykehus /ID# 201560	Drammen	Buskerud
Norway	Rikshospitalet OUS HF /ID# 202004	Oslo
Portugal	Unidade Local de Saúde da Guarda, EPE /ID# 224878	Guarda
Portugal	Centro Hospitalar Universitario de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 203530	Lisboa
Portugal	Unidade Local de Saúde do Alto Minho, EPE - Hospital Conde de Bertiandos /ID# 205186	Ponte de Lima	Viana Do Castelo
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE /ID# 208151	Vila Nova De Gaia	Porto
Romania	Spitalul Clinic Colentina /ID# 204889	Bucuresti
Romania	Spitalul Clinic Sf. Maria /ID# 203809	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Cluj -Napoca /ID# 204887	Cluj-Napoca	Cluj
Romania	Cabinet Medical Dr. Avram S.R.L /ID# 224336	Timisoara	Timis
Russian Federation	Kemerovo State Medical University /ID# 203676	Kemerovo	Kemerovskaya Oblast
Russian Federation	First Moscow State Medical University n.a I.M. Sechenov /ID# 203673	Moscow
Russian Federation	Moscow Regional Research and Clinical Institute n.a. Vladimirskiy (MONIKI) /ID# 221643	Moscow	Moskovskaya Oblast
Russian Federation	Practicheskaya Medicina Clinic /ID# 224612	Moscow
Russian Federation	Euromedservice /ID# 205345	Pushkin
Russian Federation	Clinical Rheumatologic Hospital No 25 /ID# 208950	St. Petersburg
Spain	Hospital Universitario A Coruna - CHUAC /ID# 224731	A Coruna
Spain	Hospital Clinic de Barcelona /ID# 201878	Barcelona
Spain	Hospital Universitario Basurto /ID# 224730	Bilbao	Vizcaya
Spain	Hospital Universitario Virgen de las Nieves /ID# 224726	Granada
Spain	Hospital Clinico Universitario San Carlos /ID# 204871	Madrid
Spain	Hospital General Universitario Gregorio Maranon /ID# 201326	Madrid
Spain	Hospital Universitario La Paz /ID# 241848	Madrid
Spain	Hospital Universitario Canarias /ID# 224928	San Cristóbal de La Laguna	Santa Cruz De Tenerife
Spain	Hospital Universitario Marques de Valdecilla /ID# 201604	Santander	Cantabria
Spain	Hospital Meixoeiro (CHUVI) /ID# 212084	Vigo	Pontevedra
Sweden	Sahlgrenska University Hospital /ID# 171405	Gothenburg	Vastra Gotalands Lan
Sweden	Skane University hospital /ID# 171407	Malmo	Skane Lan
Sweden	Karolinska University Hospital Solna /ID# 204945	Solna	Stockholms Lan
Sweden	Duplicate_Danderyds sjukhus /ID# 171404	Stockholm
Sweden	Uppsala University Hospital /ID# 171403	Uppsala
Sweden	Duplicate_Vastmanlands Sjukhus /ID# 171429	Vasteras
Switzerland	Universitätsspital Basel /ID# 201767	Basel	Basel-Stadt
Switzerland	Inselspital, Universitaetsspital Bern /ID# 201364	Bern
Switzerland	HFR Fribourg - Hôpital cantonal /ID# 201114	Fribourg
Switzerland	Kantonsspital St. Gallen /ID# 201134	St. Gallen	Sankt Gallen
United Kingdom	Royal United Hospitals Bath /ID# 239850	Bath	Bath And North East Somerset
United Kingdom	UH Coventry & Warwickshire /ID# 202838	Coventry
United Kingdom	Royal Devon University Healthcare NHS Foundation Trust /ID# 202834	Exeter	Devon
United Kingdom	Liverpool University University Hospitals NHS Foundation Trust /ID# 240391	Liverpool
United Kingdom	Barts Health NHS Trust /ID# 210511	London	London, City Of
United Kingdom	University Hospitals Dorset NHS Foundation Trust /ID# 202836	Poole	Dorset
United Kingdom	Portsmouth Hospitals University NHS Trust /ID# 225002	Portsmouth
United Kingdom	Southend Hospital /ID# 202839	Southend
United Kingdom	Torbay and South Devon Nhs Foundation Trust /Id# 224689	Torquay
United States	Allen Arthritis /ID# 225527	Allen	Texas
United States	University of Michigan Hospitals /ID# 168645	Ann Arbor	Michigan
United States	Arthritis and Rheumatology /ID# 170295	Atlanta	Georgia
United States	Tekton Research, Inc. /ID# 201801	Austin	Texas
United States	Ochsner Clinic Foundation /ID# 200723	Baton Rouge	Louisiana
United States	Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 169040	Boca Raton	Florida
United States	University of Vermont Medical Center /ID# 211179	Burlington	Vermont
United States	Rush University Medical Center /ID# 224581	Chicago	Illinois
United States	Precision Comprehensive Clinical Research Solutions /ID# 201798	Colleyville	Texas
United States	Western Connecticut Health Network- Germantown Rd /ID# 205071	Danbury	Connecticut
United States	Denver Arthritis Clinic /ID# 171552	Denver	Colorado
United States	Henry Ford Medical Center /ID# 207456	Detroit	Michigan
United States	Wayne State University Health Center /ID# 212755	Detroit	Michigan
United States	Aurora Rheumatology and Immunotherapy Center /ID# 201853	Franklin	Wisconsin
United States	Arizona Arthritis and Rheumatology Research - Glendale Office /ID# 204702	Glendale	Arizona
United States	AA Medical Research Center - Grand Blanc /ID# 201854	Grand Blanc	Michigan
United States	Duplicate_West Michigan Rheumatology /ID# 168647	Grand Rapids	Michigan
United States	Piedmont Arthritis Clinic, PA /ID# 212431	Greenville	South Carolina
United States	Rheum Assoc of North Alabama /ID# 168668	Huntsville	Alabama
United States	Institute of Arthritis Research /ID# 168490	Idaho Falls	Idaho
United States	West Tennessee Research Institute /ID# 209256	Jackson	Tennessee
United States	Kadlec Clinic Rheumatology /ID# 201618	Kennewick	Washington
United States	Arthritis Associates of Kingsport /ID# 212756	Kingsport	Tennessee
United States	Physician Research Collaboration, LLC /ID# 168610	Lincoln	Nebraska
United States	VA Long Beach Healthcare System /ID# 203833	Long Beach	California
United States	West Texas Clinical Research /ID# 204834	Lubbock	Texas
United States	Marietta Memorial Hospital /ID# 210834	Marietta	Ohio
United States	Ctr Arthritis & Rheumatic Dise /ID# 168667	Miami	Florida
United States	Lakes Research, LLC /ID# 210442	Miami	Florida
United States	Froedtert Memorial Lutheran Hospital /ID# 224557	Milwaukee	Wisconsin
United States	The Arthritis & Diabetes Clinic, Inc. /ID# 171199	Monroe	Louisiana
United States	Medallion Clinical Research Institute, LLC /ID# 168666	Naples	Florida
United States	Ochsner Clinic Foundation-New Orleans /ID# 171200	New Orleans	Louisiana
United States	Omega Research Group /ID# 201903	Orlando	Florida
United States	University of Pennsylvania /ID# 168655	Philadelphia	Pennsylvania
United States	Arthritis and Rheumatology Institute, PLLC /ID# 214612	Plano	Texas
United States	IRIS Research and Development, LLC /ID# 169406	Plantation	Florida
United States	Rheumatology Associates PA - Portland /ID# 225011	Portland	Maine
United States	Carilion Clinic /ID# 212928	Roanoke	Virginia
United States	University of Rochester Medical Center /ID# 213527	Rochester	New York
United States	University of Washington /ID# 201619	Seattle	Washington
United States	Louisiana State Univ HSC /ID# 202646	Shreveport	Louisiana
United States	University Clinical Research Center /ID# 202504	Somerset	New Jersey
United States	Clinvest Research LLC /ID# 208182	Springfield	Missouri
United States	Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 212761	Summerville	South Carolina
United States	Clinical Research of West Florida - Tampa /ID# 201899	Tampa	Florida
United States	Clinical Research of West Florida, Inc /ID# 201901	Tampa	Florida
United States	University of South Florida /ID# 207077	Tampa	Florida
United States	Baylor Scott & White Center for Diagnostic Medicine /ID# 213529	Temple	Texas
United States	Robin K. Dore MD, Inc /ID# 201950	Tustin	California
United States	STAT Research, Inc. /ID# 200436	Vandalia	Ohio
United States	Lovelace Scientific Resources /ID# 169041	Venice	Florida
United States	The Center for Rheumatology and Bone Research /ID# 168652	Wheaton	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Netherlands,  New Zealand,  Norway,  Portugal,  Romania,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Sustained Remission	Sustained remission is defined as having achieved absence of giant cell arteritis (GCA) signs and symptoms from Week 12 through Week 52, and adherence to the protocol-defined corticosteroid (CS) taper regimen.	At Week 52
Secondary	Percentage of Participants Achieving Sustained Complete Remission	Sustained complete remission is defined as having absence of GCA signs and symptoms; normalization of erythrocyte sedimentation rate (ESR); Normalization of high sensitivity C-reactive protein (hs-CRP) and adherence to the protocol-defined CS taper regimen.	Week 12 through Week 52
Secondary	Cumulative Corticosteroid (CS) exposure	The cumulative exposure to corticosteroid(s) is assessed.	Up to Week 52
Secondary	Time to First Disease Flare	Disease flare is defined as an event determined by the investigator to represent recurrence of GCA signs or symptoms or an ESR measurement > 30 mm/hr (attributable to GCA) AND requiring an increase in CS dose.	Up to Week 52
Secondary	Percentage of Participants Who Experience at Least 1 Disease Flare	The percentage of participants who experience at least 1 disease flare is assessed	Up to Week 52
Secondary	Percentage of Participants in Complete Remission	Complete remission is defined as having achieved absence of GCA signs and symptoms; normalization of ESR; normalization of hs-CRP and adherence to the protocol-defined CS taper regimen.	Up to Week 52
Secondary	Change from Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Score (PCS)	The SF-36 is a generic health-related quality-of-life instrument that can be used across age, disease and treatment groups and includes 8 domains: physical functioning, role limitations due to physical health problems, role limitations due to emotional health problems, social functioning, pain, energy/fatigue, emotional well-being, and general health problems.	At Week 52
Secondary	Number of Disease Flares per Participant	The number of disease flares per participant during Period 1 will be assessed.	Up to Week 52
Secondary	Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)	The FACIT-Fatigue is a 13-item electronic-patient reported outcome (ePRO) measure of fatigue, which has been validated in the general population and in other chronic diseases. The FACIT-Fatigue content and measurement validity and related reliability has been extensively tested in the psoriatic arthritis (PsA) population, with evidence of reliability, construct validity, and responsiveness.	From Week 0 to Week 52
Secondary	Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale	The Treatment Satisfaction Questionnaire for Medications (TSQM) is a generic ePRO measure of treatment satisfaction, developed to compare treatment satisfaction between medication types and conditions. TSQM comprises of 14 items to assess 4 domains (effectiveness, side effects, convenience, and global satisfaction). The TSQM items are rated on a Likert scale (1 = extremely dissatisfied to 7 = extremely satisfied). Scores for each of the 4 domains range from 0 to 100, with higher scores corresponding to higher satisfaction.	At Week 52
Secondary	Rate of CS-related Adverse Events	The rate of CS-related adverse events will be assessed.	At Week 52

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