Clinical trial NCT03117270: A Study to Assess Efficacy and Safety of Filgotinib in Ankylosing Spondylitis
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II Study to Assess the Efficacy and Safety of Filgotinib Administered for 12 Weeks to Subjects With Active Ankylosing Spondylitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ankylosing Spondylitis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2017-04-17
Enrollment: 116
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: This is a multicenter, Phase 2, double-blind, placebo-controlled study in subjects with active Ankylosing Spondylitis (AS). A total of approximately 100 subjects will be randomized to one of 2 treatment arms in a 1:1 ratio: oral filgotinib tablets q.d. or matching placebo q.d. Treatment duration will be 12 weeks. Each subject will stay in the study for a maximum of 20 weeks (from Screening visit to Follow-up visit).


Eligibility criteria: Key Inclusion Criteria:

* Male or female subjects who are ≥18 years of age on the day of signing informed consent.
* Diagnosis of moderate to severe ankylosing spondylitis with documented evidence of fulfilling the Modified New York (NY) criteria
* Have active ankylosing spondylitis with a BASDAI ≥4 (numeric rating scale \[NRS\] 0-10) and spinal pain ≥4 (0-10 NRS) (based on BASDAI question 2, see protocol) at screening and baseline.
* Have had a documented inadequate response to NSAIDs including cyclooxygenase-2 (COX-2) inhibitors.
* If using cDMARD therapy, stable dose for at lead 4 weeks prior to Baseline.
* If using non-drug therapies (including physical therapies), these should be kept stable during screening.
* Male and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use highly effective methods of contraception as described in the protocol.

Key Exclusion Criteria:

* Use of JAK inhibitors, investigational or approved, at any time, including filgotinib;
* Prior use of more than one TNF inhibitor, at any time.
* Use of oral steroids at a dose \>10 mg/day of prednisone or prednisone equivalent or at a dose that hasn't been stable for at least 4 weeks prior to baseline;
* Any therapy by intra-articular injections (e.g. corticosteroid, hyaluronate) within 4 weeks prior to screening;
* Use of more than 1 NSAID or COX-2 inhibitor.
* Contraindication to MRI.
* History of known or suspected complete ankylosis of the spine.
* Presence of very poor functional status or unable to perform self-care.
* Have undergone surgical treatment for ankylosing spondylitis within the last 12 weeks prior to screening.
* Administration of a live or attenuated vaccine within 12 weeks prior to baseline.

Primary outcomes:
measure: Ankylosing Spondylitis disease activity score (ASDAS) in filgotinib treated subjects as compared to placebo
timeFrame: week 12
Secondary outcomes:
measure: Assessment of SpondyloArthritis international Society (ASAS) in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessment by a trained joint assessor of 44 joints for tenderness (counting the number or tender joints - TJC) and swelling (counting the number of swollen joints - SJC) in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessement of the Bath Ankylosing Spondylitis Disease Activity Index in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessment of the Bath Ankylosing Spondylitis Functional Index in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessment of the Bath Ankylosing Spondylitis Metrology Index in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessment Spondyloarthritis Research Consortium of Canada MRI in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessment of the Maastricht Ankylosing Spondylitis Enthesitis Score in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessment of FACIT fatigue scale in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessment of SF-36 health survey in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Assessment of Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) in filgotinib treated subjects as compared to placebo
timeFrame: week 12
measure: Difference between filgotinib treated subjects and placebo subjects in the number of Adverse events
timeFrame: from baseline until the final follow up visit (week 16)
measure: Difference in the number of filgotinib subjects and placebo subjects with abnormal Clinical laboratory evaluations
timeFrame: from baseline until the final follow up visit (week 16)
measure: Difference in the number of filgotinib treated subjects and placebo subjects with abnormal vital signs
timeFrame: from baseline until the final follow up visit (week 16)
measure: Difference between the number of filgotinib treated subjects and placebo subjects with abnormal physical examination
timeFrame: from baseline until the final follow up visit (week 16)
measure: Difference between the number of filgotinib treated subjects and placebo with abnormal ECG
timeFrame: At baseline, end of study visit (week 12) and final follow up visit (week 16)
measure: Difference between the number of filgotinib treated subjects and placebo with abnormal radiographic assessment
timeFrame: At baseline and end of study visit (week 12)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: ULB Hopital Erasme, Service de Rheumatology
city: Plovdiv
country: Bulgaria
facility: Eurohospital
city: Plovdiv
country: Bulgaria
facility: UMHAT Kaspela EOOD
city: Ruse
country: Bulgaria
facility: Medical Center "Teodora", EOOD
city: Sofia
country: Bulgaria
facility: Akademik Ivan Geshov, UMHAT "Sv. Ivan Rilski", EAD
city: Sofia
country: Bulgaria
facility: Clinic of Rheumatology, UMHAT "Sv. Ivan Rilski", EAD
city: Sofia
country: Bulgaria
facility: UMHAT "SofiaMed", OOD, Block 1
city: Stara Zagora
country: Bulgaria
facility: Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
city: Ostrava
country: Czechia
facility: Revmatologicka ambulance
city: Pardubice
country: Czechia
facility: CCBR Czech, a.s
city: Uherské Hradiště
country: Czechia
facility: MEDICAL PLUS s.r.o.
city: Tallinn
country: Estonia
facility: OÜ Innomedica
city: Bytom
country: Poland
facility: Centrum Medyczne SILESIANA Sp z oo
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia-Centrum Medyczne Nowa Sol
city: Poznań
country: Poland
facility: Ai Centrum Medyczne sp. z o.o. sp.k.
city: Toruń
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z, Przychodnia Specjalistyczna
city: Warsaw
country: Poland
facility: Centrum Medyczne AMED, Warszawa Targowek
city: Santiago de Compostela
country: Spain
facility: Corporacio Sanitaria Parc Tauli, Servicio de Reumatologia
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa, Servicio de Reumatologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena, Dept. of Rheumatology
city: Kharkiv
country: Ukraine
facility: CI of Healthcare Kharkiv CCH #8 Dept of Rheumatology Kharkiv MA of PGE of MOHU, Ch of Cardiology and Funct Diagnostics
city: Kiev
country: Ukraine
facility: CNI Consultative and Diagnostic Center of Pecherskyi District of Kyiv, Department of Therapy
city: Kiev
country: Ukraine
facility: SI NSС M.D. Strazhesko Institute of Cardiology of NAMSU, Unit of Non-coronary HD&Rh
city: L'viv
country: Ukraine
facility: CH of State Border Service of Ukraine (Military Base 2522) Dept of Therapy, D.Halytskyi Lviv NMU, Ch of Family Medicine & Dermatology, Venereology
city: Poltava
country: Ukraine
facility: M.V. Sklifosovskyi Poltava RCH Dept of Rheumatology HSEIU UMSA, Ch of Family Medicine and Therapy
city: Ternopil'
country: Ukraine
facility: CI of TRC
city: Uzhgorod
country: Ukraine
facility: A.Novak Transcarpathian Regional Clinical Hospital, Dept of Rheumatology
city: Vinnytsia
country: Ukraine
facility: M.I. Pyrogov VRCH Dept of Rheumatology M.I. Pyrogov VNMU, Ch of IM #1
city: Vinnytsia
country: Ukraine
facility: SRI of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU, Un of Therapy and CRh Dept of Therapy
city: Vinnytsya
country: Ukraine
facility: MCIC MC LLC Health Clinic, Unit of Cardiology and Rheumatology
Study officials:
affiliation: Galapagos NV
name: Pille Harrison, MD, DPhil, MRCP (UK)
role: STUDY_DIRECTOR
References:
citation: Maksymowych WP, Ostergaard M, Landewe R, Barchuk W, Liu K, Gilles L, Hendrikx T, Besuyen R, Baraliakos X. Filgotinib decreases both vertebral body and posterolateral spine inflammation in ankylosing spondylitis: results from the TORTUGA trial. Rheumatology (Oxford). 2022 May 30;61(6):2388-2397. doi: 10.1093/rheumatology/keab758.
citation: Maksymowych WP, Ostergaard M, Landewe R, Barchuk W, Liu K, Tasset C, Gilles L, Hendrikx T, Besuyen R, Baraliakos X. Impact of filgotinib on sacroiliac joint magnetic resonance imaging structural lesions at 12 weeks in patients with active ankylosing spondylitis (TORTUGA trial). Rheumatology (Oxford). 2022 May 5;61(5):2063-2071. doi: 10.1093/rheumatology/keab543.
citation: van der Heijde D, Baraliakos X, Gensler LS, Maksymowych WP, Tseluyko V, Nadashkevich O, Abi-Saab W, Tasset C, Meuleners L, Besuyen R, Hendrikx T, Mozaffarian N, Liu K, Greer JM, Deodhar A, Landewe R. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet. 2018 Dec 1;392(10162):2378-2387. doi: 10.1016/S0140-6736(18)32463-2. Epub 2018 Oct 22.