|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Diseases [C] - Musculoskeletal Diseases [C05]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10028395 - Musculoskeletal and connective tissue disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|Evaluate the effect of filgotinib compared to placebo on the signs and symptoms of ankylosing spondylitis, as assessed by the ASDAS at Week 12.
|Secondary objectives of the trial
|Evaluate the effect of filgotinib compared to placebo on:
- The signs and symptoms of ankylosing spondylitis
- Physical function
- Spinal mobility
- Spinal and sacroiliac joint inflammation
- Quality of life
Evaluate the safety and tolerability of filgotinib
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|Subjects will have the option to participate in a PK sub-study (separate consent), requiring additional blood samples to be collected at different time points as specified in the protocol.
|Principal 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 (see protocol) for ankylosing spondylitis at screening, having radiographic sacroiliitis confirmed by central reading (historical radiographs up to 12 months are considered appropriate).
• 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.
• Screening serum high-sensitivity CRP (hsCRP) ≥0.3 mg/dL.
• Have had a documented inadequate response to 2 or more NSAIDs including cyclooxygenase-2 (COX-2) inhibitors at the therapeutic dose range for a total duration of at least 4 weeks (less than 4 weeks permitted in cases of documented intolerance).
• 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.
|Principal exclusion criteria
|• Use of JAK inhibitors, investigational or approved, at any time, including filgotinib;
• Prior use of more than one TNF inhibitor (including proposed biosimilars with demonstrated equivalence to an approved TNF inhibitor for efficacy in a clinical study), at any time. Prior use of one TNF inhibitor is allowed, with the following minimum washout periods prior to screening:
- Etanercept: 4 weeks
- Adalimumab, certolizumab pegol, golimumab: 8 weeks
- Infliximab: 12 weeks;
• 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. If an NSAID or COX-2 inhibitor is used, it must not exceed maximum doses permitted, as per local labeling and must have been used at a stable dose for at least 2 weeks prior to baseline. In addition, subjects are permitted to take acetylsalicylic acid at a dose of ≤325 mg q.d. for cardiac prophylaxis;
• 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.
|E.5 End points
|Primary end point(s)
|Change from baseline in the ASDAS at week 12
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
• The signs and symptoms of ankylosing spondylitis, as assessed by:
- Change from baseline in the ASDAS
- Percentage of patients achieving ASAS20, ASAS40, ASAS 5/6 response and ASAS
- Change from baseline in 44-joint count
- Proportions of subjects who experience clinically important improvement (decrease
of ASDAS from baseline ≥1.1), major improvement (decrease of ASDAS from
baseline ≥2.0), and inactive disease (ASDAS <1.3)
- Change from baseline in the individual components of the ASAS response criteria
and the ASDAS
- Percentage of patients achieving BASDAI 50% response (BASDAI50) and ≥2 units
improvement in BASDAI (ΔBASDAI≥2)
- Change from baseline in BASDAI
• Physical function, as assessed by change from baseline in BASFI
• Spinal mobility, as assessed by change from baseline in BASMI linear and in the individual components of the BASMI criteria, chest expansion and occiput-to-wall distance.
• Spinal and sacroiliac joint inflammation as assessed by change from baseline in SPARCC MRI score of sacroiliac joints and spine.
• Enthesitis, as assessed by change from baseline in MASES.
• Quality of life, as assessed by change from baseline in FACIT-Fatigue, SF-36, and ASQoL scores.
Incidence of AEs, SAEs, and discontinuations due to AEs, as well as changes in laboratory results, ECGs, physical examination and vital signs.
|Timepoint(s) of evaluation of this end point
|Various time points throughout the trial as specified in the protocol
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months