A Study Evaluating the Effect of Filgotinib in Participants With Active Axial Spondyloarthritis

Phase 3

Active, not recruiting

• Conditions: Axial Spondyloarthritis
• Interventions: Drug: Filgotinib; Drug: Placebo

• Registration Number: NCT05785611
• Lead Sponsor: Alfasigma S.p.A.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-14
• Study First Submitted QC: 2023-03-14
• Study First Posted: 2023-03-27
• Study Start: 2023-04-05
• Primary Completion: 2024-09-04
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-17
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 495

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non-radiographic Part (Study B) Filgotinib	Filgotinib	Participants will receive filgotinib 200 mg or placebo to match filgotinib. Participants will receive blinded treatment until Week 16. After that participants with an age under 65 and without certain health risks will enter open label period and will receive filgotinib 200 mg until Week 52. Participants reaching an ASDAS \<2.1 at weeks 40 and 52, will enter dose de-escalation phase and will be randomized to filgotinib 200 or 100 mg until Week 104. Participants, with an age of 65 or above or with certain health risks, will enter open label period until Week 104 and will receive 100 or 200 mg filgotinib a day, depending on their axSpA symptoms. The maximum duration of treatment period will be up to Week 104.
Non-radiographic Part (Study B) Filgotinib	Placebo	Participants will receive filgotinib 200 mg or placebo to match filgotinib. Participants will receive blinded treatment until Week 16. After that participants with an age under 65 and without certain health risks will enter open label period and will receive filgotinib 200 mg until Week 52. Participants reaching an ASDAS \<2.1 at weeks 40 and 52, will enter dose de-escalation phase and will be randomized to filgotinib 200 or 100 mg until Week 104. Participants, with an age of 65 or above or with certain health risks, will enter open label period until Week 104 and will receive 100 or 200 mg filgotinib a day, depending on their axSpA symptoms. The maximum duration of treatment period will be up to Week 104.
Radiographic Part (Study A) Filgotinib	Placebo	Participants will receive filgotinib 200 mg or placebo to match filgotinib. Participants will receive blinded treatment until Week 16. After that participants with an age under 65 and without certain health risks will enter open label period and will receive filgotinib 200 mg until Week 52. Participants reaching an Ankylosing Spondylitis Disease Activity Score (ASDAS) \<2.1 at weeks 40 and 52, will enter dose de-escalation phase and will be randomized to filgotinib 200 or 100 mg until Week 104. Participants, with an age of 65 or above or with certain health risks, will enter open label period until Week 104 and will receive 100 or 200 mg filgotinib a day, depending on their axSpA symptoms. The maximum duration of treatment period will be up to Week 104.
Radiographic Part (Study A) Filgotinib	Filgotinib	Participants will receive filgotinib 200 mg or placebo to match filgotinib. Participants will receive blinded treatment until Week 16. After that participants with an age under 65 and without certain health risks will enter open label period and will receive filgotinib 200 mg until Week 52. Participants reaching an Ankylosing Spondylitis Disease Activity Score (ASDAS) \<2.1 at weeks 40 and 52, will enter dose de-escalation phase and will be randomized to filgotinib 200 or 100 mg until Week 104. Participants, with an age of 65 or above or with certain health risks, will enter open label period until Week 104 and will receive 100 or 200 mg filgotinib a day, depending on their axSpA symptoms. The maximum duration of treatment period will be up to Week 104.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving SpondyloArthritis International Society 40% improvement (ASAS40) Response (Yes/No) at Week 16	Week 16

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) (linear score) at Week 16	Week 16
Change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score of Sacroiliac Joints (SIJs) at Week 16	Week 16
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16	Week 16
Change from baseline in Ankylosing Spondylitis DiseaseActivity Score with C-reactive protein (ASDASCRP) at Week 16	Week 16
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), TE Serious Adverse Events, and TEAEs Leading to Treatment Discontinuation at Week 16	Week 16
Change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 16	Week 16

Trial Locations

Locations (129)

Medical Center Teodora; 🇧🇬 Ruse, Bulgaria

Cliniques Universitaires de Bruxelles Hopital Erasme; 🇧🇪 Brussels, Belgium

ReumaClinic; 🇧🇪 Genk, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

CHU Helora; 🇧🇪 Mons, Belgium

Medical Center Rodopimed; 🇧🇬 Kardzhali, Bulgaria

MC Medconsult Pleven; 🇧🇬 Pleven, Bulgaria

UMHAT Plovdiv AD; 🇧🇬 Plovdiv, Bulgaria

UMHAT Eurohospital Plovdiv; 🇧🇬 Plovdiv, Bulgaria

Medical Center UNIMED EOOD; 🇧🇬 Plovdiv, Bulgaria

Medical Center 1 Sevlievo; 🇧🇬 Sevlievo, Bulgaria

DCC Ascendent EOOD; 🇧🇬 Sofia, Bulgaria

UMHAT Sofiamed OOD; 🇧🇬 Sofia, Bulgaria

Dcc Focus 5 Meoh Ood; 🇧🇬 Sofia, Bulgaria

Dcc Focus 5 Meoh; 🇧🇬 Sofia, Bulgaria

DCC XVII-Sofia EOOD; 🇧🇬 Sofia, Bulgaria

Medical Center Hera; 🇧🇬 Sofia, Bulgaria

Medical Center N I PIROGOV; 🇧🇬 Sofia, Bulgaria

Military Medical Academy MHAT; 🇧🇬 Sofia, Bulgaria

UMHAT Stoyan Kirkovich AD; 🇧🇬 Stara Zagora, Bulgaria

CHC Rijeka Immunology Department; 🇭🇷 Rijeka, Croatia

Poliklinika Bonifarm; 🇭🇷 Zagreb, Croatia

Poliklinika K-Centar; 🇭🇷 Zagreb, Croatia

Lekarna U Revmatologickeho; 🇨🇿 Prague, Nove Mesto, Czechia

Fakultni nemocnice u sv Anny, Interni klinika; 🇨🇿 Brno, Czechia

Revmaclinic s r o; 🇨🇿 Brno, Czechia

Lekarna BENU; 🇨🇿 Brno, Czechia

Revmatologie s r o; 🇨🇿 Brno, Czechia

CCR Ostrava; 🇨🇿 Ostrava, Czechia

Vesalion Revma ambulance; 🇨🇿 Ostrava, Czechia

Artroscan s r o; 🇨🇿 Ostrava, Czechia

ARTHROHELP s r o; 🇨🇿 Pardubice, Czechia

CCR Czech a s; 🇨🇿 Pardubice, Czechia

MUDR. Zuzana URBANOVA Revmatologie; 🇨🇿 Prague, Czechia

Fakultni nemocnice Motol; 🇨🇿 Prague, Czechia

Medical Plus Sro; 🇨🇿 Uherske Hradiste, Czechia

Clinical Research Centre; 🇪🇪 Tartu, Estonia

PV Medical Services; 🇨🇿 Zlín, Czechia

APHP Hopital Ambroise Pare; 🇫🇷 Boulogne Billancourt, France

Meditrials OU; 🇪🇪 Tartu, Estonia

Hopital Edouard Herriot; 🇫🇷 Lyon, France

CHR d'Orleans; 🇫🇷 Orleans Cedex 2, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Benite Cedex, France

Hopital Charles Nicolle; 🇫🇷 Rouen, France

Charite Medizinische Klinik I; 🇩🇪 Berlin, Germany

Hamburger Rheuma II; 🇩🇪 Hamburg, Germany

Rheumazentrum Ruhrgebiet; 🇩🇪 Herne, Germany

Klinische Forschung im med; 🇩🇪 Planegg, Germany

Universitatsklinikum Wurzburg; 🇩🇪 Wurzburg, Germany

General Hospital of Athens Laiko; 🇬🇷 Athens, Greece

University General Hospital "Attikon"; 🇬🇷 Athens, Greece

Revita Rheumatologiai Kft; 🇭🇺 Budapest, Hungary

University of Debrecen; 🇭🇺 Debrecen, Hungary

Reumatologiai es Immunologiai; 🇭🇺 Pecs, Hungary

Vita Verum Medical; 🇭🇺 Szekesfehervar, Hungary

Obudai Egeszsegugyi Centrum; 🇭🇺 Zalaegerszeg, Hungary

Istituto Ortopedico Rizzoli; 🇮🇹 Bologna, Italy

Azienda Ospedaliera Universitaria Luigi Vanvitelli; 🇮🇹 Napoli, Italy

Policlinico Paolo Giaccone; 🇮🇹 Palermo, Italy

Policlinico Uni Campus Bio-Med; 🇮🇹 Rome, Italy

Ospedale SM Misericordia; 🇮🇹 Udine, Italy

Policlinico Universitario Agostino Gemelli; 🇮🇹 Rome, Italy

Chonnam National University Hospital; 🇰🇷 Gwangju, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Hanyang University Seoul Hospital; 🇰🇷 Seoul, Korea, Republic of

Konkuk University Medical Center; 🇰🇷 Seoul, Korea, Republic of

Gangnam Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Kyung Hee University Hospital at Gangdong; 🇰🇷 Seoul, Korea, Republic of

Kaunas City Polyclinic; 🇱🇹 Kaunas, Lithuania

Kaunas Hospital of LUHSCP; 🇱🇹 Kaunas, Lithuania

Klaipeda University Hospital, Public Institution; 🇱🇹 Klaipėda, Lithuania

Vilnius UH Santariskiu Clinics; 🇱🇹 Vilnius, Lithuania

Medisch Spectrum Twente; 🇳🇱 Enschede, Netherlands

UMCG; 🇳🇱 Groningen, Netherlands

Zuyderland Medisch Centrum; 🇳🇱 Heerlen, Netherlands

Medisch Centrum Leeuwarden; 🇳🇱 Leeuwarden, Netherlands

S.C Centrul Medical Unirea SR; 🇷🇴 Târgu-Mureş, Romania

Clinresco Centres Pty Ltd,; 🇿🇦 Kempton Park, South Africa

Arthritis Clinical Trial Centre; 🇿🇦 Pinelands, South Africa

Emmed Research; 🇿🇦 Pretoria, South Africa

Winelands Medical Research Centre; 🇿🇦 Stellenbosch, South Africa

Hospital Marina Baixa; 🇪🇸 Alicante, Spain

UH Parc Tauli; 🇪🇸 Barcelona, Spain

Hospital Universitario Basurto; 🇪🇸 Bilbao, Spain

HU Reina Sofia; 🇪🇸 Córdoba, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

HU Marques de Valdecilla; 🇪🇸 Santander, Spain

Clinica GAIAS Santiago; 🇪🇸 Santiago De Compostela, Spain

HU Virgen Macarena; 🇪🇸 Sevilla, Spain

UH Virgen de Valme; 🇪🇸 Sevilla, Spain

Kaohsiung Veterans General Hospital; 🇨🇳 Kaohsiung, Taiwan

Kaohsiung Chang Gung Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Taipei Medical University Hospital; 🇨🇳 Taipei city, Taiwan

Royal United Hospital Bath NHS Foundation Trust; 🇬🇧 Bath, United Kingdom

Norfolk & Norwich University Hospital; 🇬🇧 Norwich, United Kingdom

Ilocos Training and Regional Medical Center; 🇵🇭 San Fernando, La Union, Philippines

Ospital Ng Makati; 🇵🇭 Makati City, Metro Manila, Philippines

Lipa Medix Medical Center; 🇵🇭 Lipa City, Philippines

Mary Mediatrix Medical Center; 🇵🇭 Lipa City, Philippines

Medical Center Manila; 🇵🇭 Manila, Philippines

The Medical City Clark, Mabalacat; 🇵🇭 Pampanga, Philippines

St. Luke's Medical Center; 🇵🇭 Quezon City, Philippines

Far Eastern University - Dr. Nicanor Reyes Medical Foundation; 🇵🇭 Quezon City, Philippines

ZDROWIE Osteo Medic; 🇵🇱 Bialystok, Poland

Centrum Kliniczno Badawcze; 🇵🇱 Elblag, Poland

Silmedic sp. z o. o; 🇵🇱 Katowice, Poland

Reumed Spolka z o o; 🇵🇱 Lubin, Poland

KO-MED Centra Kliniczne; 🇵🇱 Staszów, Poland

Twoja Przychodnia NCM; 🇵🇱 Nowa Sol, Poland

ETYKA Osrodek Badan Klinicznyc; 🇵🇱 Olsztyn, Poland

TPO Centrum Medyczne; 🇵🇱 Opole, Poland

AI Centrum Medyczne; 🇵🇱 Poznan, Poland

Solumed Medical Center; 🇵🇱 Poznań, Poland

Twoja Przychodnia PCM; 🇵🇱 Poznań, Poland

MICS Medical Center Torun; 🇵🇱 Toruń, Poland

Instytut Reumatologii im. Eleonory Reicher; 🇵🇱 Warsawa, Poland

Klinika Reuma Park; 🇵🇱 Warsawa, Poland

MICS Centrum Medyczne; 🇵🇱 Warszawa, Poland

ETG Warszawa; 🇵🇱 Warszawa, Poland

FutureMeds Wroclaw; 🇵🇱 Wrocław, Poland

Sj de Urgenta Bacau; 🇷🇴 Bacau, Romania

S.C Centrul Medical de Diagnostic si Tratament Ambulator Neomed S.R.L; 🇷🇴 Braşov, Romania

SC Delta Health Care SRL; 🇷🇴 Bucharest, Romania

Spitalul Clinic Judetean de Urgenta; 🇷🇴 Cluj-Napoca, Romania

Aqua Med Consulting SRL; 🇷🇴 Constanta, Romania

SC Medisof Diagnostic SRL; 🇷🇴 Craiova, Romania

Centrul Medical Unirea SRL; 🇷🇴 Iaşi, Romania

Sc Medaudio Optica Srl; 🇷🇴 Ramnicu Valcea, Romania