A Phase 3 program evaluating the effect of filgotinib in subjects with active axial spondyloarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alfasigma S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

21 Jun 2023 → ongoing

Decision date (initial)

2023-05-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Alfasigma S.p.A

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Pharmacodynamic

To compare the efficacy of filgotinib 200 mg versus placebo on signs and symptoms

Secondary objectives 5

1. To compare the efficacy of filgotinib 200 mg versus placebo on disease activity
2. To compare the efficacy of filgotinib 200 mg versus placebo on physical function
3. To compare the efficacy of filgotinib 200 mg versus placebo on health-related outcomes
4. To compare the efficacy of filgotinib 200 mg versus placebo on spinal mobility
5. To evaluate the safety and tolerability of filgotinib

Conditions and MedDRA coding

axial spondyloarthritis

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

At Sponsor’s discretion.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Ambulatory female or male subjects >=18 years of age, on the date of signing the informed consent form (ICF)
2. Have an established diagnosis of axSpA by a rheumatologist (or other specialist with expertise in diagnosing axSpA)
3. Study A (r-axSpA): Meet Assessment of SpondyloArthritis International Society (ASAS) classification criteria with radiographic sacroiliitis on X-ray as follows: a. History of back pain >=12 weeks and age at onset of back pain <45 years, AND b. Have radiographic bilateral grade 2-4 sacroiliitis or unilateral grade 3-4 sacroiliitis, based on New York grading system, confirmed by central reading. Historical radiographs up to 6 months old are considered appropriate if they are accepted by the central reader. Otherwise, a new radiograph will be obtained during the screening period, AND c. >=1 spondyloarthritis (SpA) feature.
4. Study B (nr- axSpA): Meet ASAS classification criteria without radiographic sacroiliitis on X-ray as follows: a. History of back pain >= 12 weeks and age at onset of back pain <45 years, AND b. No radiographic bilateral grade 2-4 sacroiliitis or unilateral grade 3-4 sacroiliitis, AND c. Presence of sacroiliitis on MRI (based on central reading) and at least 1 SpA feature* or when positive for human leukocyte antigen (HLA)-B27: having at least 2 SpA features*, AND d. Have objective signs of inflammation, by sacroiliitis on MRI or elevated CRP *SpA features: inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn’s/colitis, good response to NSAIDs, family history for SpA, HLA-B27, elevated CRP.
5. Have active axSpA at screening and Day 1 defined by: • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >=4 (numeric rating scale [NRS] 0-10), AND • Spinal pain score >=4 (0-10 NRS) (based on BASDAI question 2)
6. Have a history of inadequate response to >=2 NSAIDs at the maximum dose of NSAIDs used in axSpA for >=2 weeks each (a total duration of NSAID trial >=4 weeks) or intolerance to >=2 NSAIDs for the treatment of axSpA
7. Subjects who are bDMARD(s) experienced; defined as below. - Subjects designated as bDMARD(s)-IR must have received not more than 2 bDMARD(s), that was/were administered in accordance with its/their labeling and discontinued due to: o Non-response (primary or secondary) after a minimum treatment of 12 weeks, and /or o Intolerance (defined as having experienced an adverse reaction [e.g. an infusion/injection reaction, an infection, a laboratory test change, etc] irrespective of treatment duration) - Subjects designated as bDMARD(s) non-IR have previously received bDMARD(s) and have discontinued these due to other reasons than non-response or intolerance (e.g. economic reasons, treatment as part of a clinical study, other, or unknown).
8. If continuing conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during the study, subjects are permitted to use only a maximum of 2 csDMARDs and must have been on this treatment for >=12 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. In addition, methotrexate (MTX) use may not be combined with leflunomide during the study

Exclusion criteria 13

1. Prior exposure to a Janus kinase inhibitor, investigational or approved, at any time, including filgotinib.
2. Active autoimmune disease other than those listed above, that would interfere with assessment of study parameters or increase risk to the subject by participating in the study (e.g. uncontrolled uveitis, uncontrolled thyroiditis, transverse myelitis, current peptic ulcer disease or prior history of severe diverticulitis [i.e. requiring hospitalization] or previous gastrointestinal perforation), per judgment of investigator
3. History of opportunistic infection, or immunodeficiency syndrome, which would put the subject at risk, as per investigator judgment
4. Subject has any other condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g. compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. For subjects at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past (>10 pack-years) and those at increased risk of cancer, the investigator should carefully consider if participation is in the best interest of the subject.
5. Active infection that is clinically significant, as per judgment of the investigator, or history of a serious infection (requiring hospitalization or systemic antibiotics) within 12 weeks prior to screening.
6. Contraindication to MRI or any condition that would interfere with the ability to perform an MRI
7. Use of any opioid analgesic at average daily doses >30 mg/day of morphine (or equivalent) or use of unstable doses of any opioid analgesic <=2 weeks prior to Day 1
8. Use of any of the following systemic immunomodulating therapies <= 4 weeks prior to Day 1, including, but not limited to: 6-mercaptopurine, azathioprine, cyclosporine or other calcineurin inhibitors (e.g. sirolimus, tacrolimus), MTX if being discontinued, mycophenolate, antimalarials (e.g. hydroxychloroquine, chloroquine) if being discontinued, or sulfasalazine if being discontinued
9. Complete spinal ankylosis defined as the presence of consecutive bridging syndesmophytes in >=5 segments on the lateral radiograph (assessed by the central reader)
10. Have undergone surgical treatments for peripheral manifestation of axSpA, including synovectomy or arthroplasty, or major surgery (requiring regional block or general anesthesia) <=12 weeks prior to Day 1 or planned major surgery during the study
11. Have a diagnosis of any generalized musculoskeletal disorder, e.g. generalized osteoarthritis, or systemic inflammatory condition other than axSpA such as, but not limited to, gout, rheumatoid arthritis, juvenile chronic arthritis, psoriatic arthritis (PsA), reactive arthritis, SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) Syndrome, systemic lupus erythematosus, systemic vasculitis, scleroderma, inflammatory myopathy, mixed connective tissue disease, fibromyalgia, post-acute coronavirus 19 (COVID-19) syndrome, and any overlapping syndrome. Note: Prior history of reactive or other types of inflammatory arthritis is permitted if there is documentation of change in diagnosis to axSpA or additional diagnosis of axSpA.
12. Have active Crohn's disease (CD) or active ulcerative colitis (UC). Note: subjects may be enrolled if they have had a history of inflammatory bowel disease (IBD), including CD and UC, but have had no exacerbation within 6 months prior to Day 1, and, if currently on treatment, must be on stable treatment for >=6 months prior to Day 1 and this treatment should be allowed per protocol.
13. Subject has a history of malignancy or myelo- or lymphoproliferative disorder, including NMSC, excised and curatively treated non-metastatic basal cell carcinoma, squamous cell carcinoma of the skin, or in situ uterine cervical carcinoma within the past 5 years prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To compare the efficacy of filgotinib 200 mg versus placebo at week 16 on achieving ASAS40 response (Y/N)

Secondary endpoints 6

1. To compare the efficacy of filgotinib 200 mg versus placebo at week 16 on change from baseline in Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDASCRP)
2. To compare the efficacy of filgotinib 200 mg versus placebo at week 16 on change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) score of sacroiliac joints (SIJs)
3. To compare the efficacy of filgotinib 200 mg versus placebo at week 16 on change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
4. To compare the efficacy of filgotinib 200 mg versus placebo at week 16 on change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
5. To compare the efficacy of filgotinib 200 mg versus placebo at week 16 on change from baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) (linear score)
6. To compare the efficacy of filgotinib 200 mg versus placebo at week 16 on frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alfasigma S.p.A.

Sponsor organisation

Alfasigma S.p.A.

Address

Via Ragazzi Del '99 5

City

Bologna

Postcode

40133

Country

Italy

Scientific contact point

Organisation

Galapagos

Contact name

Lien Gheyle

Public contact point

Organisation

Galapagos

Contact name

Lien Gheyle

Third parties 7

Locations

15 EU/EEA countries · 113 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 508 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications