Clinical trial NCT05785611: A Study Evaluating the Effect of Filgotinib in Participants With Active Axial Spondyloarthritis
Official title: A Phase 3 Randomized, Placebo-controlled, Double-blind, Parallel-group Program to Evaluate Efficacy and Safety of Filgotinib in Adult Subjects With Active Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Keywords: chronic inflammatory disease
Lead sponsor: Alfasigma S.p.A.
Sponsor class: INDUSTRY
First posted: 2023-03-27
Enrollment: 495
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 study is comparing 200 milligrams (mg) of filgotinib a day with a placebo to see if filgotinib helps to treat Axial Spondyloarthritis (axSpA) and is safe to use. The study will also be comparing 200 mg with 100 mg filgotinib a day to see if the lower dose also helps to treat axSpA.


Eligibility criteria: Key Inclusion Criteria:

* Have an established diagnosis of axSpA by a rheumatologist (or other specialist with expertise in diagnosing axSpA).
* Study A (r-axSpA): Meet Assessment of SpondyloArthritis International Society (ASAS) classification criteria with radiographic sacroiliitis on X-ray as follows:

  1. History of back pain \>=12 weeks and age at onset of back pain \<45 years, AND
  2. Have radiographic bilateral grade 2-4 sacroiliitis or unilateral grade 3-4 sacroiliitis, based on New York grading system, confirmed by central reading, AND,
  3. \>=1 spondyloarthritis (SpA) feature.
* Study B (nr- axSpA): Meet ASAS classification criteria without radiographic sacroiliitis on X-ray as follows:

  1. History of back pain \>= 12 weeks and age at onset of back pain \<45 years, AND
  2. No radiographic bilateral grade 2-4 sacroiliitis or unilateral grade 3-4 sacroiliitis, AND,
  3. Presence of sacroiliitis on MRI (based on central reading) and at least 1 SpA feature or when positive for human leukocyte antigen (HLA)-B27: having at least 2 SpA features, AND
  4. Have objective signs of inflammation, by sacroiliitis on MRI or elevated CRP.
* Have active axSpA at screening and Day 1 defined by:

  * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) \>=4 (numeric rating scale \[NRS\] 0-10), AND
  * Spinal pain score \>=4 (0-10 NRS) (based on BASDAI question 2),
* Have a history of inadequate response to \>=2 NSAIDs at the maximum dose of NSAIDs used in axSpA for \>=2 weeks each (a total duration of NSAID trial \>=4 weeks) or intolerance to \>=2 NSAIDs for the treatment of axSpA.
* Participants who are biologic disease-modifying antirheumatic drug (BDMARD)(s) experienced; defined as below.

  * Participants designated as bDMARD(s)-inadequate responder(IR) must have received not more than 2 bDMARD(s), that was/were administered in accordance with its/their labeling and discontinued due to:

    * Non-response (primary or secondary) after a minimum treatment of 12 weeks, and /or
    * Intolerance (defined as having experienced an adverse reaction \[e.g. an infusion/injection reaction, an infection, a laboratory test change, etc\] irrespective of treatment duration)
  * Participants designated as bDMARD(s) non-IR have previously received bDMARD(s) and have discontinued these due to other reasons than non-response or intolerance (e.g. economic reasons, treatment as part of a clinical study, other, or unknown).
* If continuing conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during the study, participants are permitted to use only a maximum of 2 csDMARDs and must have been on this treatment for \>=12 weeks prior to screening, with a stable dose and route of administration (defined as no change in prescription) for \>4 weeks prior to Day 1.
* For participants aged 65 years or above on the date of signing the informed consent form (ICF), the investigator should carefully consider if participation is in the best interest of the participant.

Key Exclusion Criteria:

* Prior exposure to a Janus kinase inhibitor, investigational or approved, at any time, including filgotinib.
* Use of any opioid analgesic at average daily doses \>30 mg/day of morphine (or equivalent) or use of unstable doses of any opioid analgesic \<=2 weeks prior to Day 1.
* Use of any of the following systemic immunomodulating therapies \<= 4 weeks prior to Day 1, including, but not limited to: 6-mercaptopurine, azathioprine, cyclosporine or other calcineurin inhibitors (e.g. sirolimus, tacrolimus), methotrexate if being discontinued, mycophenolate, antimalarials (e.g. hydroxychloroquine, chloroquine) if being discontinued, or sulfasalazine if being discontinued.
* Complete spinal ankylosis defined as the presence of consecutive bridging syndesmophytes in \>=5 segments on the lateral radiograph (assessed by the central reader).
* Have undergone surgical treatments for peripheral manifestation of axSpA, including synovectomy or arthroplasty, or major surgery (requiring regional block or general anesthesia) \<=12 weeks prior to Day 1 or planned major surgery during the study.
* Have a diagnosis of any generalized musculoskeletal disorder, e.g. generalized osteoarthritis, or systemic inflammatory condition other than axSpA.
* Have active Crohn's disease (CD) or active ulcerative colitis (UC). Note: participants may be enrolled if they have had a history of inflammatory bowel disease (IBD), including CD and UC, but have had no exacerbation within 6 months prior to Day 1, and, if currently on treatment, must be on stable treatment for \>=6 months prior to Day 1 and this treatment should be allowed per protocol.
* Active autoimmune disease that would interfere with assessment of study parameters or increase risk to the participant by participating in the study (e.g. uncontrolled uveitis, uncontrolled thyroiditis, transverse myelitis, current peptic ulcer disease or prior history of severe diverticulitis \[i.e. requiring hospitalization\] or previous gastrointestinal perforation), per judgment of investigator,
* History of opportunistic infection, or immunodeficiency syndrome, which would put the participant at risk, as per investigator judgment,
* Active infection that is clinically significant, as per judgment of the investigator, or history of a serious infection (requiring hospitalization or systemic antibiotics) within 12 weeks prior to screening.
* Participant has a history of malignancy or myelo- or lymphoproliferative disorder, including non-melanoma skin cancer (NMSC), excised and curatively treated non-metastatic basal cell carcinoma, squamous cell carcinoma of the skin, or in situ uterine cervical carcinoma within the past 5 years prior to screening.
* Participant has any other condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g. compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. For participants at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past (\>10 pack-years) and those at increased risk of cancer, the investigator should carefully consider if participation is in the best interest of the participant.
* Contraindication to magnetic resonance imaging (MRI).

Primary outcomes:
measure: Percentage of Participants Achieving SpondyloArthritis International Society 40% improvement (ASAS40) Response (Yes/No) at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Change from baseline in Ankylosing Spondylitis DiseaseActivity Score with C-reactive protein (ASDASCRP) at Week 16
timeFrame: Week 16
measure: Change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score of Sacroiliac Joints (SIJs) at Week 16
timeFrame: Week 16
measure: Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16
timeFrame: Week 16
measure: Change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 16
timeFrame: Week 16
measure: Change from baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) (linear score) at Week 16
timeFrame: Week 16
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), TE Serious Adverse Events, and TEAEs Leading to Treatment Discontinuation at Week 16
timeFrame: Week 16
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires de Bruxelles Hopital Erasme
city: Genk
country: Belgium
facility: ReumaClinic
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Mons
country: Belgium
facility: CHU Helora
city: Kardzhali
country: Bulgaria
facility: Medical Center Rodopimed
city: Pleven
country: Bulgaria
facility: MC Medconsult Pleven
city: Plovdiv
country: Bulgaria
facility: UMHAT Plovdiv AD
city: Plovdiv
country: Bulgaria
facility: UMHAT Eurohospital Plovdiv
city: Plovdiv
country: Bulgaria
facility: Medical Center UNIMED EOOD
city: Ruse
country: Bulgaria
facility: Medical Center Teodora
city: Sevlievo
country: Bulgaria
facility: Medical Center 1 Sevlievo
city: Sofia
country: Bulgaria
facility: DCC Ascendent EOOD
city: Sofia
country: Bulgaria
facility: UMHAT Sofiamed OOD
city: Sofia
country: Bulgaria
facility: Dcc Focus 5 Meoh Ood
city: Sofia
country: Bulgaria
facility: Dcc Focus 5 Meoh
city: Sofia
country: Bulgaria
facility: DCC XVII-Sofia EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Hera
city: Sofia
country: Bulgaria
facility: Medical Center N I PIROGOV
city: Sofia
country: Bulgaria
facility: Military Medical Academy MHAT
city: Stara Zagora
country: Bulgaria
facility: UMHAT Stoyan Kirkovich AD
city: Rijeka
country: Croatia
facility: CHC Rijeka Immunology Department
city: Zagreb
country: Croatia
facility: Poliklinika Bonifarm
city: Zagreb
country: Croatia
facility: Poliklinika K-Centar
city: Prague
country: Czechia
facility: Lekarna U Revmatologickeho
state: Nove Mesto
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv Anny, Interni klinika
city: Brno
country: Czechia
facility: Revmaclinic s r o
city: Brno
country: Czechia
facility: Lekarna BENU
city: Brno
country: Czechia
facility: Revmatologie s r o
city: Ostrava
country: Czechia
facility: CCR Ostrava
city: Ostrava
country: Czechia
facility: Vesalion Revma ambulance
city: Ostrava
country: Czechia
facility: Artroscan s r o
city: Pardubice
country: Czechia
facility: ARTHROHELP s r o
city: Pardubice
country: Czechia
facility: CCR Czech a s
city: Prague
country: Czechia
facility: MUDR. Zuzana URBANOVA Revmatologie
city: Prague
country: Czechia
facility: Fakultni nemocnice Motol
city: Uherske Hradiste
country: Czechia
facility: Medical Plus Sro
city: Zlín
country: Czechia
facility: PV Medical Services
city: Tartu
country: Estonia
facility: Clinical Research Centre
city: Tartu
country: Estonia
facility: Meditrials OU
city: Boulogne Billancourt
country: France
facility: APHP Hopital Ambroise Pare
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Orleans Cedex 2
country: France
facility: CHR d'Orleans
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Berlin
country: Germany
facility: Charite Medizinische Klinik I
city: Hamburg
country: Germany
facility: Hamburger Rheuma II
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Planegg
country: Germany
facility: Klinische Forschung im med
city: Wurzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Athens
country: Greece
facility: General Hospital of Athens Laiko
city: Athens
country: Greece
facility: University General Hospital "Attikon"
city: Budapest
country: Hungary
facility: Revita Rheumatologiai Kft
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Pecs
country: Hungary
facility: Reumatologiai es Immunologiai
city: Szekesfehervar
country: Hungary
facility: Vita Verum Medical
city: Zalaegerszeg
country: Hungary
facility: Obudai Egeszsegugyi Centrum
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Luigi Vanvitelli
city: Palermo
country: Italy
facility: Policlinico Paolo Giaccone
city: Rome
country: Italy
facility: Policlinico Uni Campus Bio-Med
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Udine
country: Italy
facility: Ospedale SM Misericordia
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
city: Kaunas
country: Lithuania
facility: Kaunas Hospital of LUHSCP
city: Kaunas
country: Lithuania
facility: Kaunas City Polyclinic
city: Klaipėda
country: Lithuania
facility: Klaipeda University Hospital, Public Institution
city: Vilnius
country: Lithuania
facility: Vilnius UH Santariskiu Clinics
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: UMCG
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: San Fernando
country: Philippines
facility: Ilocos Training and Regional Medical Center
state: La Union
city: Makati City
country: Philippines
facility: Ospital Ng Makati
state: Metro Manila
city: Lipa City
country: Philippines
facility: Lipa Medix Medical Center
city: Lipa City
country: Philippines
facility: Mary Mediatrix Medical Center
city: Manila
country: Philippines
facility: Medical Center Manila
city: Pampanga
country: Philippines
facility: The Medical City Clark, Mabalacat
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
city: Quezon City
country: Philippines
facility: Far Eastern University - Dr. Nicanor Reyes Medical Foundation
city: Bialystok
country: Poland
facility: ZDROWIE Osteo Medic
city: Elblag
country: Poland
facility: Centrum Kliniczno Badawcze
city: Katowice
country: Poland
facility: Silmedic sp. z o. o
city: Lubin
country: Poland
facility: Reumed Spolka z o o
city: Lublin
country: Poland
facility: KO-MED Centra Kliniczne
city: Nowa Sol
country: Poland
facility: Twoja Przychodnia NCM
city: Olsztyn
country: Poland
facility: ETYKA Osrodek Badan Klinicznyc
city: Opole
country: Poland
facility: TPO Centrum Medyczne
city: Poznan
country: Poland
facility: AI Centrum Medyczne
city: Poznań
country: Poland
facility: Solumed Medical Center
city: Poznań
country: Poland
facility: Twoja Przychodnia PCM
city: Staszów
country: Poland
facility: KO-MED Centra Kliniczne
city: Toruń
country: Poland
facility: MICS Medical Center Torun
city: Warsawa
country: Poland
facility: Instytut Reumatologii im. Eleonory Reicher
city: Warsawa
country: Poland
facility: Klinika Reuma Park
city: Warszawa
country: Poland
facility: MICS Centrum Medyczne
city: Warszawa
country: Poland
facility: ETG Warszawa
city: Wrocław
country: Poland
facility: FutureMeds Wroclaw
city: Bacau
country: Romania
facility: Sj de Urgenta Bacau
city: Braşov
country: Romania
facility: S.C Centrul Medical de Diagnostic si Tratament Ambulator Neomed S.R.L
city: Bucharest
country: Romania
facility: SC Delta Health Care SRL
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta
city: Constanta
country: Romania
facility: Aqua Med Consulting SRL
city: Craiova
country: Romania
facility: SC Medisof Diagnostic SRL
city: Iaşi
country: Romania
facility: Centrul Medical Unirea SRL
city: Ramnicu Valcea
country: Romania
facility: Sc Medaudio Optica Srl
city: Târgu-Mureş
country: Romania
facility: S.C Centrul Medical Unirea SR
city: Kempton Park
country: South Africa
facility: Clinresco Centres Pty Ltd,
city: Pinelands
country: South Africa
facility: Arthritis Clinical Trial Centre
city: Pretoria
country: South Africa
facility: Emmed Research
city: Stellenbosch
country: South Africa
facility: Winelands Medical Research Centre
city: Alicante
country: Spain
facility: Hospital Marina Baixa
city: Barcelona
country: Spain
facility: UH Parc Tauli
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto
city: Córdoba
country: Spain
facility: HU Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santander
country: Spain
facility: HU Marques de Valdecilla
city: Santiago De Compostela
country: Spain
facility: Clinica GAIAS Santiago
city: Sevilla
country: Spain
facility: HU Virgen Macarena
city: Sevilla
country: Spain
facility: UH Virgen de Valme
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taipei city
country: Taiwan
facility: Taipei Medical University Hospital
city: Bath
country: United Kingdom
facility: Royal United Hospital Bath NHS Foundation Trust
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University Hospital
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director
role: STUDY_DIRECTOR
References: