FILGOTINIB for Juvenile idiopathic arthritis

Inclusion criteria

• {"criterion_text":"- Subject and/or parent(s)/legal guardian must be able and willing to comply with the CSP requirements and must sign and date the informed consent form as approved by the IEC/IRB and as described in Section 12.7.2, prior to any screening evaluations."}
• {"criterion_text":"- Subject with a body mass index (BMI) within the 5th to 95th percentiles for the age and gender (based on World Health Organization BMI charts, Appendix 3). Subject must have a minimum weight of 15 kg."}
• {"criterion_text":"- Subject must be able and willing to comply with restrictions on prior and concomitant medication (as described in Section 6.3.2)."}
• {"criterion_text":"- Subject must meet the ILAR classification for 1 of the following categories and have, according to the investigator’s judgment, moderately to severely active disease that is not adequately controlled with his/her current therapy. a. RF-positive polyarthritis b. RF-negative polyarthritis c. Oligoarthritis d. Psoriatic arthritis e. ERA Note: Historical HLA-B27 results are considered appropriate for ERA diagnosis during screening. f. sJIA with active arthritis without active systemic features, or with active systemic features that are stable in the prior 6 months of time of enrollment"}
• {"criterion_text":"- Subject with intolerance or a history of inadequate response to at least one of the following medications for the treatment of JIA, administered for at least 12 weeks, based on current treatment guidelines: conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and bDMARDs (including MTX) and non-steroidal anti-inflammatory drugs for ERA and psoriatic arthritis."}
• {"criterion_text":"- Female or male subjects from 8 to <18 years of age, on the date of signing the informed consent form (ICF)."}
• {"criterion_text":"- Female subjects of childbearing potential (i.e. who have passed menarche) must have a negative highly sensitive urine pregnancy test."}
• {"criterion_text":"- Female subject of childbearing potential who are, in the opinion of the investigator, potentially sexually active and at risk for pregnancy, must agree to use contraception/preventive exposure measures (as described in Section 6.3.1.1.2)."}
• {"criterion_text":"- Female subject of non-childbearing potential must meet the definition in Section 6.3.1.1.1."}

Exclusion criteria

• {"criterion_text":"- Subject with persistent oligoarthritis."}
• {"criterion_text":"- Currently on any therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex, or atypical mycobacteria)."}
• {"criterion_text":"- Subject presenting any signs or symptoms of SARS-Cov-2 infection, as detected at baseline following careful physical examination (e.g. cough, fever, headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, etc.) (BMJ, 2020a, 2020b), should undergo testing, even if fully vaccinated against SARS-CoV-2, as per locally applicable standard criteria to diagnose SARS-CoV-2 infection, and be excluded if positive."}
• {"criterion_text":"- Subject has a history of malignancy or myelo- or lymphoproliferative disorder prior to screening."}
• {"criterion_text":"- Subject has a history or presence of clinically significant abnormalities detected on 12-lead electrocardiogram (ECG) of either rhythm or conduction e.g. known long QT syndrome or a QTcF >450 ms detected on the 12-lead ECG. A first-degree atrioventricular block will not be considered as a significant abnormality."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Subject with a history of macrophage activation syndrome within 6 months prior to the screening visit."}
• {"criterion_text":"- Subject with psychological or cognitive difficulties that might interfere with study participation."}
• {"criterion_text":"- Subject for whom results of the following laboratory tests performed at the central laboratory at screening meet any of the criteria below: a. Hemoglobin <8.0 g/dL (SI: <80 g/L) b. Neutrophils <1.05 x 10 3 3 cells/mm (SI: <1.05 x 10 9 cells/L) c. Lymphocytes <0.5 x 10 3 3 cells/mm (SI: <0.5 x 10 9 cells/L) d. ALT or AST >=1.5x ULN e. Total bilirubin level >=2x ULN unlessor >=3x ULN if the subject has been diagnosed with Gilbert's disease and this is clearly documented f. CrCl <60 mL/min/1.73 m 2 by the revised bedside Schwartz equation"}
• {"criterion_text":"- Subject has taken any prohibited therapies within the defined washout periods before the planned first dose of IP."}
• {"criterion_text":"- Subject concurrently participates or participated in a drug, drug/device or biologic investigational research study within 4 weeks or 5 half-lives of the IP, whichever is longer, prior to the first dose."}
• {"criterion_text":"- Subject with undifferentiated arthritis."}
• {"criterion_text":"- Subject has a known hypersensitivity to IP ingredients or history of a significant allergic reaction to IP ingredients as determined by the investigator."}
• {"criterion_text":"- Female subject is pregnant or breast feeding or intending to become pregnant or breastfeed during the study."}
• {"criterion_text":"- Investigator or other study staff or relative thereof who is directly involved in the conduct of the study."}
• {"criterion_text":"- Subject has any condition or circumstances that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures and requirements (e.g. active alcohol or drug abuse)."}
• {"criterion_text":"- Subject has a history of chronic alcohol abuse, intravenous drug abuse, or other illicit drug abuse within the 2 years prior to screening."}
• {"criterion_text":"- Subject is institutionalized by virtue of an order issued by either the judicial or the administrative authorities or has a dependence on the sponsor or investigator."}
• {"criterion_text":"- Subject with any other any other rheumatic, inflammatory, or immunologic disease (e.g. inflammatory bowel disease, hypogammaglobulinemia, systemic lupus erythematosus, or uncontrolled uveitis)."}
• {"criterion_text":"- Subject has evidence of active HBV infection: subjects with positive HBsAg at screening are excluded from the study. Subjects with positive hepatitis B virus core antibody (HBcAb) and negative HBsAg require reflex testing for HBV DNA. Subjects with positive HBV DNA at screening will be excluded. Subjects with positive HBcAb and negative HBV DNA are eligible per investigator judgment but may require prophylactic treatment in accordance with HBV treatment guidelines/local standard of care and require ongoing viral monitoring with blood tests for HBV DNA."}
• {"criterion_text":"- Subject has chronic HCV infection, as defined by positive HCV Ab at screening and detectable HCV viremia. Subjects with positive HCV Ab must undergo reflex HCV RNA testing, and subjects with HCV RNA positivity will be excluded. Subjects with positive HCV Ab and negative HCV RNA are eligible per investigator judgment but require ongoing viral monitoring with blood tests for HCV RNA (see Section 8.3.2)."}
• {"criterion_text":"- Subject has a history of or a current immunosuppressive condition (e.g. HIV infection)."}
• {"criterion_text":"- Subject meets 1 of the following TB criteria at screening: • A history of active or currently active TB (regardless of treatment). • A positive QuantiFERON®-TB Gold Plus In-Tube test at screening. Note: If the test result is indeterminate, it may be repeated once; if indeterminate or positive on retest, subject is not eligible."}
• {"criterion_text":"- Active infection that is clinically significant, as per judgment of the investigator."}
• {"criterion_text":"- Subject with a history of complicated herpes zoster infection (with multi-dermatomal, disseminated, ophthalmic, or central nervous system involvement)."}

Primary endpoints

• {"endpoint_text":"- PK parameters of filgotinib and its major metabolite GS-829845 (including maximum observed plasma concentration at steady state [Cmax,ss], area under the plasma concentration-time curve over the dosing interval at steady state [AUC0-24,ss], and area under the plasma concentration-time curve over the dosing interval at steady state for the effective exposure [AUCeff,ss]).","definition_or_measurement_approach":"Measurement of PK parameters of filgotinib and metabolite GS-829845 including Cmax,ss, AUC0-24,ss and AUCeff,ss (plasma concentration-time sampling at steady state)."}

Secondary endpoints

• {"endpoint_text":"- Frequency and severity of treatment-emergent adverse events (TEAEs), TEAEs of interest, serious TEAEs, and TEAEs leading to treatment discontinuation.","definition_or_measurement_approach":"Safety assessment by recording and grading TEAEs, serious TEAEs and TEAEs leading to discontinuation (standard adverse event reporting)."}
• {"endpoint_text":"- Acceptability of the commercially developed film-coated tablets and of the minitablets as measured by the Pediatric Oral Medicine Acceptability Questionnaire for Patients (POMAQ-P).","definition_or_measurement_approach":"Patient-reported acceptability measured using the POMAQ-P questionnaire."}

France

Earliest CTIS Part Ii Submission Date

19-12-2023

Latest Decision Or Authorization Date

02-08-2024

Processing Time Days

227

Number Of Sites

2

Number Of Participants

10

Poland

Earliest CTIS Part Ii Submission Date

18-12-2023

Latest Decision Or Authorization Date

06-08-2024

Processing Time Days

232

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

18-12-2023

Latest Decision Or Authorization Date

30-07-2024

Processing Time Days

225

Number Of Sites

3

Number Of Participants

20

Germany

Earliest CTIS Part Ii Submission Date

18-12-2023

Latest Decision Or Authorization Date

03-09-2025

Processing Time Days

625

Number Of Sites

3

Number Of Participants

10

Primary sponsor

Full Name

Alfasigma S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

IQVIA Limited

Responsibilities

Feasibility, Identification and Qualification of Investigators; Submission to Competent Authorities and Ethics Committees; other operational tasks (sponsorDuties codes: 1,12,15,5,6)

Name

QPS Netherlands B.V.

Responsibilities

Laboratory/clinical operations support (sponsorDuties code: 4)

Name

Labcorp Central Laboratory Services S.a.r.l.

Responsibilities

Central laboratory services (sponsorDuties code: 4)

Name

Medidata Solutions Inc.

Responsibilities

Data/IT platform support (sponsorDuties code: 6)

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1, 12, 15 (Feasibility, Identification and Qualification of Investigators; Submission to Competent Authorities and Ethics Committees), 5, 6","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"QPS Netherlands B.V.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}