Clinical trial NCT03502616: Efficacy and Safety of Tofacitinib in Subjects With Active Ankylosing Spondylitis (AS)
Official title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, STUDY OF THE EFFICACY AND SAFETY OF TOFACITINIB IN SUBJECTS WITH ACTIVE ANKYLOSING SPONDYLITIS (AS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ankylosing Spondylitis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-04-18
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if tofacitinib is safe and effective in subjects with active ankylosing spondylitis.


Eligibility criteria: Inclusion Criteria:

* Has a diagnosis of Ankylosing Spondylitis (AS) based on the Modified New York Criteria for AS (1984).
* Must have a radiograph of SI joints (AP Pelvis) documenting diagnosis of AS.
* Has active disease despite nonsteroidal anti-inflammatory drug (NSAID) therapy or intolerant to NSAIDs.

Exclusion Criteria:

* History of known or suspected complete ankylosis of the spine.
* History of allergies, intolerance or hypersensitivity to lactose or tofacitinib.
* History of any other rheumatic disease.
* Any subject with condition affecting oral drug absorption.

Primary outcomes:
measure: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS)20 Response at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Achieving Ankylosing Spondylitis (ASAS)40 Response at Week 16
timeFrame: Week 16
measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: Baseline up to Week 16 and Baseline up to Week 48
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity
timeFrame: Baseline up to Week 16 and Baseline up to Week 48
measure: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline up to Week 16 and Baseline up to Week 48
measure: Number of Participants With Vital Signs Abnormalities
timeFrame: Baseline up to Week 16 and Baseline up to Week 48
measure: Number of Participants With Abnormalities in Physical Examination
timeFrame: Screening, Week 16, and Week 48
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline up to Week 16, Baseline up to Week 48
measure: Percentage of Participants Achieving ASAS20 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48
timeFrame: Weeks 2, 4, 8, 12, 24, 32, 40 and 48
measure: Percentage of Participants Achieving ASAS40 Response at Weeks 2, 4, 8, 12, 24, 32, 40 and 48
timeFrame: Weeks 2, 4, 8, 12, 24, 32, 40 and 48
measure: Change From Baseline in Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Weeks 16 and 48
timeFrame: Baseline, Weeks 16 and 48
measure: Change From Baseline in Short-Form-36 Health Survey-Version 2 Acute (SF-36v2) Score at Weeks 16 and 48
timeFrame: Baseline, Weeks 16 and 48
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Cervical Rotation Angle at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Intermalleolar Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lateral Spinal Flexion at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Lumbar Flexion (Modified Schober) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Scores: Tragus-to-wall Distance at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Linear Method Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Experience Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Impact Domain Scores at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Patient's Global Assessment of Disease (PGA) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Patient's Assessment of Spinal Pain: Total Back Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Patient's Assessment of Spinal Pain: Nocturnal Spinal Pain at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Inflammation (Morning Stiffness) Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Percentage of Participants Achieving ASAS 5/6 Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Percentage of Participants Achieving ASAS Partial Remission at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Percentage of Participants With Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Clinically Important Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Percentage of Participants Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Major Improvement Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Percentage of Participants Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein (ASDAS[CRP]) Inactive Disease Response at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Swollen Joint Count (SJC) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in Spinal Mobility (Chest Expansion ) at Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40 and 48
measure: Change From Baseline in EuroQol 5 Dimensions 3 Levels (EQ-5D-3L) Score at Weeks 16 and 48
timeFrame: Baseline, Weeks 16 and 48
measure: Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score (mm) at Weeks 16 and 48
timeFrame: Baseline, Weeks 16 and 48
measure: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to Health Problem at Weeks 16 and 48
timeFrame: Baseline, Weeks 16 and 48
measure: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Due to Health Problem at Weeks 16 and 48
timeFrame: Baseline, Weeks 16 and 48
measure: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Due to Health Problem at Weeks 16 and 48
timeFrame: Baseline, Weeks 16 and 48
measure: Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Due to Health Problem at Weeks 16 and 48
timeFrame: Baseline, Weeks 16 and 48
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rheumatology Associates of North Alabama, PC
state: Alabama
city: Gilbert
country: United States
facility: Arizona Arthritis & Rheumatology Associates, P.C.
state: Arizona
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: San Diego
country: United States
facility: Rheumatology Center of San Diego PC
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
city: Tustin
country: United States
facility: Robin K. Dore, MD, Inc.
state: California
city: Bridgeport
country: United States
facility: New England Research Associates, LLC
state: Connecticut
city: Stamford
country: United States
facility: Advanced Radiology
state: Connecticut
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: Miami
country: United States
facility: Southcoast Research Center, Inc.
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Lexington
country: United States
facility: Bluegrass Community Research, Inc
state: Kentucky
city: Wheaton
country: United States
facility: Center for Rheumatology and Bone Research
state: Maryland
city: Durham
country: United States
facility: M3-Emerging Medical Research, LLC
state: North Carolina
city: Middleburg Heights
country: United States
facility: Paramount Medical Research and Consulting, LLC
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research
state: Pennsylvania
city: Summerville
country: United States
facility: Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology
state: South Carolina
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: Corpus Christi
country: United States
facility: Adriana Pop-Moody MD - Clinic PA
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Houston
country: United States
facility: Clinical Research Unit
state: Texas
city: Houston
country: United States
facility: Investigational Drug Services
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital Imaging
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research LLC
state: Texas
city: Plano
country: United States
facility: Trinity Universal Research Associates, Inc.
state: Texas
city: The Woodlands
country: United States
facility: Advanced Rheumatology of Houston
state: Texas
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC
state: Washington
city: Maroochydore
country: Australia
facility: Pacific Radiology,
state: Queensland
city: Maroochydore
country: Australia
facility: Rheumatology Research Unit Sunshine Coast
state: Queensland
city: Camberwell
country: Australia
facility: Emeritus Research Pty. Ltd.
state: Victoria
city: East Melbourne
country: Australia
facility: Melbourne Radiology Clinic
state: Victoria
city: Subiaco
country: Australia
facility: SKG Radiology
state: Western Australia
city: Subiaco
country: Australia
facility: Western Cardiology
state: Western Australia
city: Victoria Park
country: Australia
facility: RK Will Pty Ltd
state: Western Australia
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for active treatment "Kaspela" EOOD
city: Sofia
country: Bulgaria
facility: Diagnostic-Consulting Center XVII - Sofia
city: Sofia
country: Bulgaria
facility: Medical Centre Synexus Sofia EOOD
city: Trois-Rivieres
country: Canada
facility: Centre de Recherche Musculo-Squelettique
state: Quebec
city: Quebec
country: Canada
facility: G.R.M.O. (Groupe de recherche en maladies osseuses) Inc.
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hosptial of Wenzhou Medical University
state: Zhejiang
city: Shanghai
country: China
facility: Rheumatology and Immunology Department, Shanghai Changzheng Hospital
city: Ostrava
country: Czechia
facility: Lekarna Rezidence Nova Karolina
city: Ostrava
country: Czechia
facility: CCBR Ostrava s.r.o.
city: Pardubice
country: Czechia
facility: BENU Lekarna
city: Pardubice
country: Czechia
facility: CCR, Czech a.s.
city: Uherske Hradiste
country: Czechia
facility: Lekarna Hradebni, s.r.o.
city: Uherske Hradiste
country: Czechia
facility: Uherskohradistska nemocnice, a.s.
city: Uherske Hradiste
country: Czechia
facility: Medical Plus s.r.o.
city: TOURS Cedex 9
country: France
facility: CHRU de Tours, Hopital Trousseau
city: Budapest
country: Hungary
facility: Qualiclinic K ft
city: Kistarcsa
country: Hungary
facility: Pest megyei Flór Ferenc Kórház, Reumatológia-és Fizioterápiás Osztály
city: Veszprém
country: Hungary
facility: VITAL MEDICAL CENTER (VITÁL-MEDICINA Kft.)
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Katowice
country: Poland
facility: Geo Medical Sp. z.o.o Szpital Geo Medical
city: Katowice
country: Poland
facility: Moja Przychodnia
city: Katowice
country: Poland
facility: C.M. Silmedic Sp. z o.o.
city: Krakow
country: Poland
facility: Malopolskie Badania Kliniczne Sp. z o.o. s.k.
city: Krakow
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Krakow
country: Poland
facility: Centrum Medyczne LUX MED
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne S.C.
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Zaklad Radiologii
city: Lublin
country: Poland
facility: Top Medical
city: Lublin
country: Poland
facility: Zespol Poradni Specjalistycznych REUMED, Wallenroda Filia nr 1
city: Poznan
country: Poland
facility: NZOZ JAMED Pracownia Rentgenowska Jerema Antoszewski
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj
city: Sochaczew
country: Poland
facility: Klinika Alfa
city: Sochaczew
country: Poland
facility: RCMed Oddzial Sochaczew
city: Sochaczew
country: Poland
facility: Szpital Powiatowy w Sochaczewie
city: Warszawa
country: Poland
facility: Szpital Sw. Elzbiety, Mokotowskie Centrum Medyczne, Zaklad Diagnostyki
city: Warszawa
country: Poland
facility: "Reumatika - Centrum Reumatologii" NZOZ
city: Wroclaw
country: Poland
facility: Centrum Medyczne Oporow
city: Wroclaw
country: Poland
facility: Centrum Medyczne Medix
city: Kemerovo
country: Russian Federation
facility: Limited Liability Company Medical Center "Rheuma-Med"
city: Orenburg
country: Russian Federation
facility: State Budgetary Healthcare Institution "Orenburg Regional Clinical Hospital"
city: Saint-Petersburg
country: Russian Federation
facility: Limited Liability Company "Sanavita"
city: Saratov
country: Russian Federation
facility: State Healthcare Institution "Regional Clinical Hospital"
city: Smolensk
country: Russian Federation
facility: RSBHI "Smolensk Regional Clinical Hospital"
city: Vladimir
country: Russian Federation
facility: Limited Liability Company "BioMed"
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi Ibn-i Sina Hastanesi
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi, Ibn-i Sina Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi, Ic Hastaliklari Anabilim
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi, Ic Hastaliklari
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi
city: Istanbul
country: Turkey
facility: Marmara Univ. Istanbul Pendik Egitim ve Arastirma Hastanesi
city: Izmir
country: Turkey
facility: Izmir Katip Celebi Univ Ataturk Egitim ve Arastirma Hastanesi
city: Izmir
country: Turkey
facility: Izmir Katip Celebi Univ. Ataturk Egitim ve Arastirma Hastanesi
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital # 3, Rheumatology Department
city: Lviv
country: Ukraine
facility: Lviv Communal Clinical Hospital #4, Rheumatology department
city: Lviv
country: Ukraine
facility: Military-Medical Clinical Center (Clinical Hospital with 200 beds) of State Border Guard Service of
city: Ternopil
country: Ukraine
facility: Ternopil University Hospital, Department of Rheumatology,
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrohov, rheumatology department,
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Cella D, Lenderking WR, Chongpinitchai P, Bushmakin AG, Dina O, Wang L, Cappelleri JC, Navarro-Compan V. Functional Assessment of Chronic Illness Therapy-Fatigue is a reliable and valid measure in patients with active ankylosing spondylitis. J Patient Rep Outcomes. 2022 Sep 23;6(1):100. doi: 10.1186/s41687-022-00508-0.
citation: Navarro-Compan V, Wei JC, Van den Bosch F, Magrey M, Wang L, Fleishaker D, Cappelleri JC, Wang C, Wu J, Dina O, Fallon L, Strand V. Effect of tofacitinib on pain, fatigue, health-related quality of life and work productivity in patients with active ankylosing spondylitis: results from a phase III, randomised, double-blind, placebo-controlled trial. RMD Open. 2022 Jun;8(2):e002253. doi: 10.1136/rmdopen-2022-002253.
citation: Deodhar A, Sliwinska-Stanczyk P, Xu H, Baraliakos X, Gensler LS, Fleishaker D, Wang L, Wu J, Menon S, Wang C, Dina O, Fallon L, Kanik KS, van der Heijde D. Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2021 Aug;80(8):1004-1013. doi: 10.1136/annrheumdis-2020-219601. Epub 2021 Apr 27.