Identification of Synovial Biomarkers of Response to Ixekizumab in Refractory Psoriatic Arthritis: the Precise Study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Hospital Of Ferrara

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-06-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of the study is to evaluate if synovial biomarkers modifications in culture supernatants and cellular homogenates (after in vitro administration of IXE in assays of different cells/tissues obtained from refractory PsA patients) predict clinical response to systemic IXE at 12 weeks.

Secondary objectives 1

1. Secondary objectives are: -To evaluate if relevant biomarkers modifications, after in vitro administration of IXE, relate to ultrasonography (US) response at 12 weeks; -To evaluate if baseline histopathological data (based on Krenn’s score (45,46), and number of CD20, CD3, CD68, CD117, CD31, evaluated using immunohistochemistry - IHC) relate to clinical response to systemic IXE at 12 weeks; -To evaluate if synovial biomarkers modifications, after in vitro administration of IXE, predict clinical response to systemic IXE at 24 weeks; -To deepen the synovial effect of IXE in synovial explant cultures and FLS/PBMCs co-cultures; -To establish if a concentration-dependent effect of IXE could be responsible of relevant results obtained; -To confirm safety of US-guided synovial biopsy procedures; to confirm reliability of US-guided synovial biopsies in collecting adequate synovial tissue to guarantee FLS cultures; to establish a reliable and reproducible method of co-culture system using PBMCs and FLS.

Conditions and MedDRA coding

PSORIATIC ARTHRITIS

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Confirmed diagnosis of PsA, according to an expert physician, and fulfilling the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria (55); 2. Age greater than or equal to 18 years; 3. Active disease (defined as 3 or more swollen joints AND 3 or more tender joints); 4. Potential indication to (new) bDMARD therapy with IXE according to treating physician opinion, in line with international and national recommendations (3,57) and product data sheet; 5. Patients refractory to previous (at least 1) csDMARDs therapies (incomplete response, loss of efficacy or adverse events), naïve to b/tsDMARDs; 6. One of the involved joints has to be appropriate for US-guided synovial biopsy; 7. Patients must provide written informed consent; 8. Oral prednisone at doses of ≤10 mg/day (stable for at least 4 weeks); 9. No concomitant csDMARDs or concomitant background csDMARDs stable for at least 4 weeks.

Exclusion criteria 1

1. 1. Contraindication to start a new bDMARD treatment course; 2. Previous treatment with bDMARDs (any, included anti-IL17A agents) or tsDMARDs (any); 3. Contraindication to US-guided synovial biopsy (e.g. uncontrolled haemostatic disorders, allergies to local anaesthetics); 4. Previous treatment with intra-articular steroids within the previous 1 month; 5. Patients with dementia or an altered mental status, which would preclude the understanding and rendering of informed consent; 6. Known allergy or hypersensitivity to any biologic therapy; 7. Administration of live attenuated vaccine(s) (LAVs) within 6 weeks of enrolment. Or intended use of LAV during the treatment period; 8. Any history of malignancy in the last 5 years except for completely resected squamous or basal cell carcinoma of the skin; 9. For women of childbearing potential: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3- months after study completion; 10. Known immunodeficiency or patients immunocompromised to an extent that participation in the study would pose and unacceptable risk to the patient; 11. Clinically relevant (chronic or acute) infections, including untreated (latent) tuberculosis, hepatitis B or C or HIV infections; 12. Subjects with other autoimmune disease, e.g. Crohn's disease, Ulcerative colitis and Graves disease, except celiac disease and hypothyroidism which do not need to be excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary clinical endpoint of this study is response to treatment at T12, which will be primarily measured as ACR20 response (59). The primary laboratory endpoints are the sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and accuracy of the test in predicting the response to the treatment [Time point: T12].

Secondary endpoints 1

1. The secondary endpoints are: - Patient-level ultrasonographic response according to multi-joint PsASon22 US score (56), measured as 20% variation in the inflammatory subscore [Time point: T12]; - Joint level ultrasonographic response according to single-joint PsASon22 US score (56) [Time point: T12]; - Other key clinical endpoints (ACR50, ACR70, DAPSA, MDA, HAQ-DI score; PGA, pain, PhGA, number of swollen/tender joints, BSA) [Time points: T12, T24]; - Response to treatment according to ACR20 res

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Hospital Of Ferrara

Sponsor organisation

University Hospital Of Ferrara

Address

Cona, Via Aldo Moro 8 Via Aldo Moro 8

City

Ferrara

Postcode

44124

Country

Italy

Scientific contact point

Organisation

University Hospital Of Ferrara

Contact name

Ettore Silvagni

Public contact point

Organisation

University Hospital Of Ferrara

Contact name

Ilaria Panzini

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 files

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

Application history

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