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

• ClinicalTrials.gov Identifier: NCT03117270
• Recruitment Status: Completed
• First Posted: April 17, 2017
• Last Update Posted: August 13, 2018
• Sponsor: Galapagos NV
• Information provided by (Responsible Party): Galapagos NV

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Ankylosing Spondylitis	Drug: filgotinib; Drug: Placebo Oral Tablet	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 7, 2017
• Actual Primary Completion Date: July 2, 2018
• Actual Study Completion Date: July 2, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Ankylosing Spondylitis disease activity score (ASDAS) in filgotinib treated subjects as compared to placebo [ Time Frame: week 12 ]
   To evaluate the effect of filgotinib on the AS disease activity score

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Belgium

ULB Hopital Erasme, Service de Rheumatology

Brussels, Belgium

Bulgaria

Eurohospital

Plovdiv, Bulgaria

UMHAT Kaspela EOOD

Plovdiv, Bulgaria

Medical Center "Teodora", EOOD

Ruse, 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

Sofia, Bulgaria

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD

Stara Zagora, Bulgaria

Czechia

Revmatologicka ambulance

Ostrava, Czechia

CCBR Czech, a.s

Pardubice, Czechia

MEDICAL PLUS s.r.o.

Uherské Hradiště, Czechia

Estonia

OÜ Innomedica

Tallinn, Estonia

Poland

Centrum Medyczne SILESIANA Sp z oo

Bytom, Poland

Twoja Przychodnia-Centrum Medyczne Nowa Sol

Nowa Sól, Poland

Ai Centrum Medyczne sp. z o.o. sp.k.

Poznań, Poland

Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z, Przychodnia Specjalistyczna

Toruń, Poland

Centrum Medyczne AMED, Warszawa Targowek

Warsaw, Poland

Spain

Corporacio Sanitaria Parc Tauli, Servicio de Reumatologia

Santiago de Compostela, Spain

Hospital Infanta Luisa, Servicio de Reumatologia

Sevilla, Spain

Hospital Universitario Virgen Macarena, Dept. of Rheumatology

Sevilla, Spain

Ukraine

CI of Healthcare Kharkiv CCH #8 Dept of Rheumatology Kharkiv MA of PGE of MOHU, Ch of Cardiology and Funct Diagnostics

Kharkiv, 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

Kiev, Ukraine

CH of State Border Service of Ukraine (Military Base 2522) Dept of Therapy, D.Halytskyi Lviv NMU, Ch of Family Medicine & Dermatology, Venereology

L'viv, Ukraine

M.V. Sklifosovskyi Poltava RCH Dept of Rheumatology HSEIU UMSA, Ch of Family Medicine and Therapy

Poltava, Ukraine

CI of TRC

Ternopil', Ukraine

A.Novak Transcarpathian Regional Clinical Hospital, Dept of Rheumatology

Uzhgorod, 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

Vinnytsia, Ukraine

MCIC MC LLC Health Clinic, Unit of Cardiology and Rheumatology

Vinnytsya, Ukraine

Sponsors and Collaborators

Galapagos NV

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Galapagos NV
• ClinicalTrials.gov Identifier: NCT03117270
• Other Study ID Numbers: GLPG0634-CL-223
• First Posted: April 17, 2017
• Last Update Posted: August 13, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Spinal Diseases; Arthritis; Joint Diseases; Axial Spondyloarthritis; Spondylarthropathies; Ankylosis