Study to measure filgotinib in the blood of children and teenagers with arthritis taking filgotinib-GLPG0634-CL-131

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alfasigma S.p.A.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

14 Feb 2024 → ongoing

Decision date (initial)

2024-01-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Galapagos NV

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

To characterize the PK of filgotinib in children and adolescents from 8 to <18 years of age with active JIA.

Secondary objectives 2

1. To evaluate the safety and tolerability of filgotinib in children and adolescents from 8 to <18 years of age with active JIA.
2. To evaluate the acceptability of the commercially developed film-coated tablets and of the minitablets in children and adolescents from 8 to <18 years of age with active JIA.

Conditions and MedDRA coding

juvenile idiopathic arthritis

Study design 4 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001619-PIP04-17

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. 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.
3. Subject must be able and willing to comply with restrictions on prior and concomitant medication (as described in Section 6.3.2).
4. 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
5. 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.
6. Female or male subjects from 8 to <18 years of age, on the date of signing the informed consent form (ICF).
7. Female subjects of childbearing potential (i.e. who have passed menarche) must have a negative highly sensitive urine pregnancy test.
8. 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).
9. Female subject of non-childbearing potential must meet the definition in Section 6.3.1.1.1.

Exclusion criteria 25

1. Subject with persistent oligoarthritis.
2. Subject with undifferentiated arthritis.
3. Subject with any other any other rheumatic, inflammatory, or immunologic disease (e.g. inflammatory bowel disease, hypogammaglobulinemia, systemic lupus erythematosus, or uncontrolled uveitis).
4. 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.
5. 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).
6. Subject has a history of or a current immunosuppressive condition (e.g. HIV infection).
7. 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.
8. Active infection that is clinically significant, as per judgment of the investigator.
9. Subject with a history of complicated herpes zoster infection (with multi-dermatomal, disseminated, ophthalmic, or central nervous system involvement).
10. Currently on any therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex, or atypical mycobacteria).
11. 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.
12. Subject has a history of malignancy or myelo- or lymphoproliferative disorder prior to screening.
13. 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.
14. 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.
15. Subject with a history of macrophage activation syndrome within 6 months prior to the screening visit.
16. Subject with psychological or cognitive difficulties that might interfere with study participation.
17. 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
18. Subject has taken any prohibited therapies within the defined washout periods before the planned first dose of IP.
19. 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.
20. Subject has a known hypersensitivity to IP ingredients or history of a significant allergic reaction to IP ingredients as determined by the investigator.
21. Female subject is pregnant or breast feeding or intending to become pregnant or breastfeed during the study.
22. Investigator or other study staff or relative thereof who is directly involved in the conduct of the study.
23. 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).
24. Subject has a history of chronic alcohol abuse, intravenous drug abuse, or other illicit drug abuse within the 2 years prior to screening.
25. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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]).

Secondary endpoints 2

1. Frequency and severity of treatment-emergent adverse events (TEAEs), TEAEs of interest, serious TEAEs, and TEAEs leading to treatment discontinuation.
2. 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).

Investigational products

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

Test 3

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

Alfasigma S.p.A.

Contact name

Valentina Agostini

Public contact point

Organisation

Alfasigma S.p.A.

Contact name

Valentina Agostini

Third parties 4

Locations

4 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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