A Phase 3 randomized, placebo-controlled, double-blind, parallel-group program to evaluate efficacy and safety of filgotinib in adult subjects with active axial spondyloarthritis

The primary objective of this Phase 3 randomized, placebo-controlled, double-blind, parallel-group study is to compare the **efficacy** of filgotinib 200 mg versus placebo on the signs and symptoms of active axial spondyloarthritis. This is clinically relevant as it aims to determine the potential of filgotinib in alleviating the clinical manifestations of this chronic inflammatory disease, which can significantly impact patient quality of life.

Secondary objectives include:

• Comparing the efficacy of filgotinib 200 mg versus placebo on disease activity.
• Comparing the efficacy of filgotinib 200 mg versus placebo on physical function.
• Comparing the efficacy of filgotinib 200 mg versus placebo on health-related outcomes.
• Comparing the efficacy of filgotinib 200 mg versus placebo on spinal mobility.
• Evaluating the safety and tolerability of filgotinib.

These secondary objectives are crucial for understanding the broader impact of filgotinib on various aspects of patient health and its overall safety profile.

The clinical trial involves a total of **95 participants** diagnosed with **axial spondyloarthritis**. The study population comprises both male and female subjects who are **18 years of age or older**. Participants were selected based on their established diagnosis of axial spondyloarthritis by a rheumatologist or a specialist with expertise in this condition. The trial includes individuals who meet the Assessment of SpondyloArthritis International Society (ASAS) classification criteria, with specific radiographic or MRI findings and a history of back pain. Participants are required to have active disease at screening and Day 1, as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or higher and a spinal pain score of 4 or higher. The study includes individuals with a history of inadequate response or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs) and those who have experience with biologic disease-modifying antirheumatic drugs (bDMARDs). Participants may continue using conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) under specific conditions. The trial population is not limited by gender, and it includes a vulnerable population. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **filgotinib** in adult subjects with active **axial spondyloarthritis**. The trial will involve the administration of **Jyseleca** 100 mg and 200 mg film-coated tablets, with a placebo-to-match (PTM) used to maintain blinding. The trial is structured to include a screening visit, multiple follow-up visits, and an end-of-study visit, with the primary endpoint being the comparison of the efficacy of filgotinib 200 mg versus placebo at week 16 on achieving ASAS40 response. Secondary endpoints include changes from baseline in various disease activity and quality of life scores at week 16.

Participants will be involved in the study for a maximum treatment period of 104 weeks, with the trial estimated to conclude by May 2026. The inclusion criteria require participants to be ambulatory adults with a confirmed diagnosis of axial spondyloarthritis, meeting specific classification criteria and demonstrating active disease at screening and Day 1. Participants must have a history of inadequate response or intolerance to at least two NSAIDs and may have prior experience with biologic DMARDs. The study will exclude individuals who do not meet these criteria or who have conditions that could interfere with the trial's objectives.

The sequence of study visits begins with an inclusion (screening) visit to assess eligibility based on the inclusion and exclusion criteria. Follow-up visits will occur at regular intervals to monitor the participants' response to treatment and any adverse events. The end-of-study visit will evaluate the overall outcomes and safety of the treatment. Participants may be withdrawn from the study early if they experience severe adverse events, fail to adhere to the study protocol, or withdraw consent. The trial's design ensures rigorous assessment of the treatment's efficacy and safety, contributing valuable data to the understanding of filgotinib's role in managing axial spondyloarthritis.

The clinical trial involves the administration of **Jyseleca** 100 mg film-coated tablets, which contain the active substance **filgotinib**. These tablets are designed for **oral use** and are manufactured by GALAPAGOS. The maximum daily dose for this formulation is 100 mg, with a total treatment period of up to 52 weeks. The pharmaceutical form is a film-coated tablet, ensuring ease of administration and patient compliance. The chemical origin of the active substance is confirmed, and the product is authorized under the marketing authorization number EU/1/20/1480/002.

Additionally, **Jyseleca** 200 mg film-coated tablets are utilized in the study, also containing the active substance **filgotinib**. These tablets are similarly intended for **oral use** and are produced by GALAPAGOS. The maximum daily dose for this formulation is 200 mg, with a total treatment period extending up to 104 weeks. The film-coated tablet form facilitates patient adherence to the dosing regimen. The chemical origin of the active substance is consistent with the 100 mg formulation, and the product holds the marketing authorization number EU/1/20/1480/004.

To maintain the blinding of the study, **Placebo-to-match (PTM)** tablets are employed. These tablets are identical in appearance to the active **filgotinib** tablets, available in both 200 mg and 100 mg dosages. The use of PTM tablets ensures that neither the participants nor the investigators can distinguish between the active treatment and the placebo, thereby preserving the integrity of the double-blind study design. The placebo tablets are administered **orally**, matching the route of administration of the active treatment.

The efficacy of filgotinib in the treatment of active axial spondyloarthritis will be assessed through a series of primary and secondary endpoints. The primary endpoint is the achievement of the ASAS40 response at week 16, comparing filgotinib 200 mg to placebo. Secondary endpoints include changes from baseline at week 16 in several measures: Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), Spondyloarthritis Research Consortium of Canada (SPARCC) MRI score of sacroiliac joints, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear score. Additionally, the frequency and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to treatment discontinuation will be evaluated.

These efficacy parameters will be measured and collected at baseline and at week 16 using validated scales and imaging techniques. The ASAS40 response is a widely recognized measure in spondyloarthritis trials, while ASDAS-CRP and SPARCC MRI scores provide insights into disease activity and inflammation. BASFI, ASQoL, and BASMI are established tools for assessing functional status, quality of life, and physical mobility, respectively. The analysis will focus on comparing the changes from baseline between the filgotinib and placebo groups to determine the treatment's efficacy.