| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037160 |
| E.1.2 | Term | Psoriatic arthritis |
| E.1.2 | System Organ Class | 100000004859 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| •To evaluate the effect of filgotinib compared to placebo in active PsA as assessed by the ACR20 response at Week 12 |
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| E.2.2 | Secondary objectives of the trial |
•To evaluate the effect of filgotinib on core domains of PsA (e.g. peripheral arthritis, psoriatic skin disease, enthesitis and dactylitis) as assessed by MDA, VLDA, ACR responses, PASI including BSA responses, SPARCC Enthesitis Index and LEI, LDI including TDC, PASDAS, DAPSA, mNAPSI, and PhGAP
•To evaluate the effect of filgotinib on physical function in active PsA as assessed by HAQ-DI
•To evaluate the effect of filgotinib on fatigue and quality of life in active PsA as assessed by FACIT-Fatigue, SF-36v2, and PsAID-12
•To evaluate the efficacy of filgotinib versus adalimumab in active PsA as assessed by ACR20
•To evaluate the safety and tolerability of filgotinib
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Skin Biopsy Substudy :
At selected investigational sites, subjects may consent to participate in an optional (lesional / non-lesional) skin biopsy research. Skin biopsy will be assessed for changes in histology and gene expression analyses including but not limited to genes related to IL23 / IL17 pathways.
MRI Investigation:
At capable sites (i.e. qualifying equipment, local regulatory approval, etc.) a subset of subjects (approximately 50 per dosing group) will undergo MRI evaluation with gadolinium. These subjects must provide consent and meet the entrance criteria for MRI in Section 4.4 of the Protocol. MRIs with gadolinium of a single hand / wrist will be performed at two time points: Screening and at the Week 16 Visit.
Biomarker Samples for Optional Future Research:
Subjects may be able to provide consent to allow the use of the remainder of their already collected biomarker and PK specimens for optional future research. The specimens collected for optional future research will be used to increase our knowledge and understanding of the biology of the PsA and related autoimmune-related arthropathy and to study the association of biomarkers with PsA pathogenesis, progression and / or treatment outcomes, including efficacy, AEs, and the processes of drug absorption and disposition. These specimens may be used also to develop biomarker or diagnostic assays and establish the performance characteristics of these assays.
Biomarker Samples for Optional Genomic Research:
Subjects may be able to consent to provide additional samples for optional genomic research. The samples will be used to identify or validate genetic markers that may increase our knowledge and understanding of the biology of the study disease and related diseases and to study the association of genetic markers with disease
pathogenesis, progression and / or treatment outcomes, including efficacy, AEs, and the processes of drug absorption and disposition.
These specimens may be used also to develop biomarker or diagnostic assays and establish the performance characteristics of these assays. |
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| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in this
study.
•Male or female subjects who are 18-75 years of age (19-75 years of age at sites in Republic of Korea. 20-75 years of age at sites in Japan and Taiwan), on the day of signing initial informed consent
•Meet Classification Criteria for Psoriatic Arthritis (CASPAR) and have a history consistent with PsA ≥6 months at Screening
•Have active PsA defined as ≥3 swollen joints (from a 66 swollen joint count [SJC]) and ≥3 tender joints (from a 68 tender joint count [TJC]) at Screening and Day 1;these may or may not be the same joints at Screening and Day 1
•Must have a documented history or active signs of at least one of the following at Screening:
Plaque psoriasis or nail changes attributed to psoriasis
•Have had inadequate response or intolerance to ≥1 csDMARD, apremilast and / or NSAID, administered over the course of ≥12 weeks for the treatment of PsA, as per local guidelines / standard of care
•If continuing csDMARD(s) during the study, subjects are permitted to use only a maximum of 2 of the drugs as outlined in Section 4.2 of the Protocol and must have been on this treatment for ≥12 consecutive 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
•Concomitant NSAIDs or corticosteroids are permitted as specified in Sections 4.2 and 4.3 of the Protocol
•Meet one of the TB screening criteria as described in Section 4.2 of the Protocol.
•Able and willing to sign the informed consent as approved by the IRB/IEC
•Able and willing to perform SC self-injections or have a caregiver able, willing, and available to administer the injections
•Subjects receiving non-prohibited medication for any reason should be on a stable dose prior to the first administration of the study drug on day 1
•A negative serum pregnancy test result at the Screening Visit and negative urine pregnancy test result at the Day 1 Visit are required for female subjects of child bearing potential
•Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
•Lactating females must agree to discontinue nursing before the study drug is administered
MRI Inclusion Criteria
•Subject must fulfill criteria for entry to the Main Study
•Subject must have PsA joint involvement at a minimum in one hand / wrist as confirmed by the investigator at Screening. The same hand / wrist (R or L) should be imaged at all subsequent MRIs, regardless of PsA activity
•Subject’s baseline MRI must fulfill at least one of the following criteria by central reading: Definitive intra-articular MRI synovitis (PsAMRIS Grade ≥2 in any applicable hand or wrist joint, or PsAMRIS Grade 1 in ≥2 applicable joints); or definitive MRI osteitis in any applicable bone
•An acceptable baseline MRI read and approved by central imaging, on or before day 28 of Screening
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|
| E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
•Known hypersensitivity to the study drug, the metabolites or the formulation excipients
•Prior PsA or psoriasis treatment with a bioDMARD
•Prior exposure to a JAK inhibitor >2 doses
•Any active / recent infection, as specified in Section 4.3 of the Protocol
•Any chronic and / or uncontrolled medical condition that would put the subject at increased risk during study participation or circumstances which may make a subject unlikely or unable to complete or comply with study procedures and requirements, per investigator judgement
•Any moderately to severely active musculoskeletal or skin disorder other than PsA or plaque psoriasis that would interfere with assessment of study parameters, as per judgement of the investigator NOTE: Prior history of reactive arthritis or axial spondyloarthritis is permitted if there is documentation of change in diagnosis to PsA or additional diagnosis of PsA
•Any history of an inflammatory arthropathy with onset before age 16 years old
•Active autoimmune disease that would interfere with assessment of study parameters or increase risk to the subject by participating in the study (e.g. uveitis, inflammatory bowel disease, uncontrolled thyroiditis, systemic vasculitis, transverse myelitis), per judgement of investigator
•Presence of any extra-articular manifestations typically associated with rheumatoid arthritis (RA), such as rheumatoid nodules, rheumatoid lung, or other signs / symptoms, as per judgement of investigator
•Pregnancy or nursing females
•Active drug or alcohol abuse, as per judgement of investigator
•Unwilling or unable to follow protocol requirements
Key MRI Exclusion Criteria
NOTE: Subject may still participate in the Main Study / LTE if ineligible for the MRI investigation. Reasons for ineligibility may include, but are not limited to:
•Inability or medical contraindication for an MRI examination (e.g. presence of a pacemaker, defibrillator, or other contraindicated implanted metallic device, such as anterior interbody cages, aneurysm clip or pedicle screws, severe claustrophobia or weight >350 lbs or >158kg.))
•Metallic fragments embedded anywhere in the body OR pigment-containing tattoos in the area of examination
•Known or potential risk of adverse reaction to gadolinium-base contrast agents, including but not limited to, allergy or compromised renal function, per investigator judgement
•Very difficult peripheral intravascular access
•Site or region was not selected by Sponsor to perform MRIs
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the ACR20 response at Week 12. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The key secondary endpoints include:
•ACR50 response at Week 12
•Change from Baseline in HAQ-DI at Week 12
•Change from Baseline in SF-36v2 physical component summary (PCS) at Week 16
•Change from Baseline in LEI at Week 16, in subjects with enthesitis at Baseline
•PASI75 response at Week 16, in subjects with psoriasis covering ≥3% of the BSA at Baseline
•MDA response at Week 16
•Change from Baseline in FACIT-Fatigue at Week 16
•Change from Baseline in LDI at Week 16, in subjects with dactylitis at Baseline
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 174 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Australia |
| Belgium |
| Bulgaria |
| Canada |
| Czech Republic |
| Estonia |
| France |
| Germany |
| Hong Kong |
| Hungary |
| Italy |
| Japan |
| Korea, Republic of |
| Mexico |
| New Zealand |
| Poland |
| Romania |
| Slovakia |
| Spain |
| Taiwan |
| Thailand |
| United Kingdom |
| United States |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of study is defined as when the last subject has completed all scheduled dosing plus their safety follow-up visit or the study has been terminated |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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