A Study to Assess Efficacy and Safety of Filgotinib in Ankylosing Spondylitis (TORTUGA)

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

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).

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Drug: filgotinib; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • ULB Hopital Erasme, Service de Rheumatology
• Bulgaria
  • Plovdiv, Bulgaria
    • Eurohospital
  • Plovdiv, Bulgaria
    • UMHAT Kaspela EOOD
  • Ruse, Bulgaria
    • Medical Center "Teodora", EOOD
  • Sofia, Bulgaria
    • Akademik Ivan Geshov, UMHAT "Sv. Ivan Rilski", EAD
  • Sofia, Bulgaria
    • Clinic of Rheumatology, UMHAT "Sv. Ivan Rilski", EAD
  • Sofia, Bulgaria
    • UMHAT "SofiaMed", OOD, Block 1
  • Stara Zagora, Bulgaria
    • Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
• Czechia
  • Ostrava, Czechia
    • Revmatologicka ambulance
  • Pardubice, Czechia
    • CCBR Czech, a.s
  • Uherské Hradiště, Czechia
    • MEDICAL Plus s.r.o.
• Estonia
  • Tallinn, Estonia
    • OU Innomedica
• Poland
  • Bytom, Poland
    • Centrum Medyczne SILESIANA Sp z oo
  • Nowa Sól, Poland
    • Twoja Przychodnia-Centrum Medyczne Nowa Sol
  • Poznań, Poland
    • Ai Centrum Medyczne Sp. Z O.O. Sp.K.
  • Toruń, Poland
    • Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z, Przychodnia Specjalistyczna
  • Warsaw, Poland
    • Centrum Medyczne AMED, Warszawa Targowek
• Spain
  • Santiago de Compostela, Spain
    • Corporacio Sanitaria Parc Tauli, Servicio de Reumatologia
  • Sevilla, Spain
    • Hospital Infanta Luisa, Servicio de Reumatologia
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena, Dept. of Rheumatology
• Ukraine
  • Kharkiv, Ukraine
    • CI of Healthcare Kharkiv CCH #8 Dept of Rheumatology Kharkiv MA of PGE of MOHU, Ch of Cardiology and Funct Diagnostics
  • Kiev, Ukraine
    • CNI Consultative and Diagnostic Center of Pecherskyi District of Kyiv, Department of Therapy
  • Kiev, Ukraine
    • SI NSС M.D. Strazhesko Institute of Cardiology of NAMSU, Unit of Non-coronary HD&Rh
  • L'viv, Ukraine
    • CH of State Border Service of Ukraine (Military Base 2522) Dept of Therapy, D.Halytskyi Lviv NMU, Ch of Family Medicine & Dermatology, Venereology
  • Poltava, Ukraine
    • M.V. Sklifosovskyi Poltava RCH Dept of Rheumatology HSEIU UMSA, Ch of Family Medicine and Therapy
  • Ternopil', Ukraine
    • CI of TRC
  • Uzhgorod, Ukraine
    • A.Novak Transcarpathian Regional Clinical Hospital, Dept of Rheumatology
  • Vinnytsia, Ukraine
    • M.I. Pyrogov VRCH Dept of Rheumatology M.I. Pyrogov VNMU, Ch of IM #1
  • Vinnytsia, Ukraine
    • SRI of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU, Un of Therapy and CRh Dept of Therapy
  • Vinnytsya, Ukraine
    • MCIC MC LLC Health Clinic, Unit of Cardiology and Rheumatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral filgotinib tablets	Drug: filgotinib; one filgotinib oral tablet q.d.
Placebo Comparator: placebo tablets	Drug: Placebo Oral Tablet; one placebo oral tablet q.d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ankylosing Spondylitis disease activity score (ASDAS) in filgotinib treated subjects as compared to placebo	To evaluate the effect of filgotinib on the AS disease activity score	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of SpondyloArthritis international Society (ASAS) in filgotinib treated subjects as compared to placebo	To evaluation the effect of filgotinib on the ASAS score in AS patients	week 12
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	To evaluate the effect of filgotinib on joint tenderness and swelling in AS patient	week 12
Assessement of the Bath Ankylosing Spondylitis Disease Activity Index in filgotinib treated subjects as compared to placebo	To assess the effect of filgotinib on BAS disease activity index in AS patients	week 12
Assessment of the Bath Ankylosing Spondylitis Functional Index in filgotinib treated subjects as compared to placebo	To assess the effect of filgotinib on BAS functional index in AS patients	week 12
Assessment of the Bath Ankylosing Spondylitis Metrology Index in filgotinib treated subjects as compared to placebo	To assess the effect of filgotinib on BAS metrology index in AS patients	week 12
Assessment Spondyloarthritis Research Consortium of Canada MRI in filgotinib treated subjects as compared to placebo	To assess the effect of filogtinib on Spondyloarthritis Research Consortium of Canada MRI in AS patients	week 12
Assessment of the Maastricht Ankylosing Spondylitis Enthesitis Score in filgotinib treated subjects as compared to placebo	To assess the effect of filgotinibe on Maastricht Ankylosing Spondylitis Enthesitis Score in AS patients	week 12
Assessment of FACIT fatigue scale in filgotinib treated subjects as compared to placebo	To assess the effect of filgotinib on FACIT fatigue scale in AS patients	week 12
Assessment of SF-36 health survey in filgotinib treated subjects as compared to placebo	To assess the effect of filgotinib on SF-36 health survey in AS patients	week 12
Assessment of Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) in filgotinib treated subjects as compared to placebo	To assess the effect of filgotinib on ASQoL in AS patients	week 12
Difference between filgotinib treated subjects and placebo subjects in the number of Adverse events	To assess safety and tolerability of filgotinib in AS patients	from baseline until the final follow up visit (week 16)
Difference in the number of filgotinib subjects and placebo subjects with abnormal Clinical laboratory evaluations	To assess safety and tolerability of filgotinib in AS patients	from baseline until the final follow up visit (week 16)
Difference in the number of filgotinib treated subjects and placebo subjects with abnormal vital signs	To assess safety and tolerability of filgotinib in AS patients	from baseline until the final follow up visit (week 16)
Difference between the number of filgotinib treated subjects and placebo subjects with abnormal physical examination	To assess safety and tolerability of filgotinib in AS patients	from baseline until the final follow up visit (week 16)
Difference between the number of filgotinib treated subjects and placebo with abnormal ECG	To assess safety and tolerability of filgotinib in AS patients	At baseline, end of study visit (week 12) and final follow up visit (week 16)
Difference between the number of filgotinib treated subjects and placebo with abnormal radiographic assessment	To assess safety and tolerability of filgotinib in AS patients	At baseline and end of study visit (week 12)

Collaborators and Investigators

• Sponsor: Galapagos NV
• Investigators: Study Director: Pille Harrison, MD, DPhil, MRCP (UK), Galapagos NV

Publications and helpful links

General Publications

• Maksymowych WP, Østergaard M, Landewé 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2017
• Primary Completion (Actual): July 2, 2018
• Study Completion (Actual): July 2, 2018

Study Registration Dates

• First Submitted: March 30, 2017
• First Submitted That Met QC Criteria: April 12, 2017
• First Posted (Actual): April 17, 2017

Study Record Updates

• Last Update Posted (Actual): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 10, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
• Other Study ID Numbers: GLPG0634-CL-223

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No