Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
260
Countries
1
Sites
20
juvenile idiopathic arthritis
to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation (Step-up strategy) and driven by the treat-to-target approach, with that of an early aggressive intervention based on a combination of conventional and biological DMARDs (Step-down strategy).
Key facts
- Sponsor
- Giannina Gaslini Institute For Scientific Hospitalization And Care
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20], Diseases [C] - Musculoskeletal Diseases [C05]
- Trial duration
- 4 Sep 2024 → ongoing
- Decision date (initial)
- 2024-09-04
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Grants: Italian Medicine Agency and Compagnia di San Paolo. IMP donated by Pfizer (Enbrel)
External identifiers
- EU CT number
- 2023-505051-43-00
- EudraCT number
- 2018-001931-27
- ClinicalTrials.gov
- NCT03728478
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation (Step-up strategy) and driven by the treat-to-target approach, with that of an early aggressive intervention based on a combination of conventional and biological DMARDs (Step-down strategy).
Conditions and MedDRA coding
juvenile idiopathic arthritis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 23.1 | PT | 10059176 | Juvenile idiopathic arthritis | 100000004859 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Newly-diagnosed and synthetic or biologic DMARD-naïve children (only treatment with 1 NSAID is allowed and no corticosteroid joint injections prior to randomization) with a JIA classified according to the following ILAR categories: i. Oligoarthritis, ii. Rheumatoid factor negative polyarthritis
- Active arthritis
- Onset of JIA symptoms no more than 6 months before randomization, IV. Age 2 to 16 years at enrolment
- Female of child-bearing potential must have a negative pregnancy test at the beginning of the trial. If sexually active, they must agree to use highly effective contraceptive measures, throughout study participation, and must have no intention of conceiving during the course of the study. Post-pubertal males must have no plans to father a child during the study and agree to use highly effective contraceptive measures if sexually active
- Ability to comply with the entire study procedures, ability to communicate meaningfully with the investigational staff, competence to give written informed consent; to be applied to the parents and/or patients, as appropriate
- Duly executed, written, informed consent/assent obtained from the parents/patient
- Age 2 to 16 years at enrolment
Exclusion criteria 7
- Classification in one of the following JIA categories: systemic arthritis, RF-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis, undifferentiated arthritis
- Patients who need systemic treatment for uveitis
- Tuberculosis related issues: patients are excluded from the study if they have: a. Active TB or a history of incompletely treated TB; b. PPD or QuantiFERON-TB positive patients (with no active disease) unless it is documented by a specialist that the patient has been adequately treated for TB and can start treatment with a biologic agent, based on the medical judgment of the study investigator and / or an infectious disease specialist; c. Suspected extrapulmonary TB infection; d. Patients at high risk of contracting TB, such as close contact with individual with active or latent TB.
- Previous treatment with any synthetic or biologic DMARD
- Any live attenuated vaccine within 4 weeks prior to the baseline visit, such as varicella-zoster, oral polio, measles, mumps or rubella vaccines and throughout the study. Killed or inactive vaccine may be permitted based on the investigator’s judgment
- Prior or current history of malignancy or any other significant concomitant illness(es) as per the treating physician evaluation
- Any of the following laboratory abnormalities based on the most recent laboratory results: a. White blood cell (WBC) count <3.50 x 103/mm3 (SI units: <3.50 x 109/L) and neutrophils < 1x109/L; b. Hemoglobin < 8.5 g/dL (SI units: <85 g/L); c. Platelet Count < 125,0000/mm3 or ≥1,000,000/mm3 (SI units: <125 x 109/L or ≥1,000 x 109/L; d. Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) ≥ 2.0 x upper limit of normal (ULN)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Clinical remission on or off medication at 12 months.
Secondary endpoints 1
- The rate of patients who achieve the JADAS/JIA ACR state of ID at any single point in time throughout the study period will be compared between the 2 arms.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
Enbrel 10 mg powder and solvent for solution for injection for paediatric use
PRD6538807 · Product
- Active substance
- Etanercept
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 7.1 mg milligram(s)
- Max total dose
- 1200 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AB01 — -
- Marketing authorisation
- EU/1/99/126/022
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Enbrel 25 mg solution for injection in pre-filled syringe
PRD6538806 · Product
- Active substance
- Etanercept
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 7.1 mg milligram(s)
- Max total dose
- 1200 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AB01 — -
- Marketing authorisation
- EU/1/99/126/013
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Enbrel 50 mg solution for injection in pre-filled syringe
PRD6538802 · Product
- Active substance
- Etanercept
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 7.1 mg milligram(s)
- Max total dose
- 1200 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AB01 — -
- Marketing authorisation
- EU/1/99/126/017
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 6
Reumaflex 50 mg/ml soluzione iniettabile, siringa preriempita
PRD11003605 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 2.9 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AX03 — -
- Marketing authorisation
- 045171434
- MA holder
- ALFASIGMA S.P.A.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Reumaflex 50 mg/ml soluzione iniettabile, siringa preriempita
PRD11003898 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 2.9 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AX03 — -
- Marketing authorisation
- 045171461
- MA holder
- ALFASIGMA S.P.A.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Reumaflex 50 mg/ml soluzione iniettabile, siringa preriempita
PRD11003614 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 2.9 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AX03 — -
- Marketing authorisation
- 045171675
- MA holder
- ALFASIGMA S.P.A.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Reumaflex 50 mg/ml soluzione iniettabile, siringa preriempita
PRD11003617 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 2.9 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AX03 — -
- Marketing authorisation
- 045171459
- MA holder
- ALFASIGMA S.P.A.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Reumaflex 50 mg/ml soluzione iniettabile, siringa preriempita
PRD11003894 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 2.9 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AX03 — -
- Marketing authorisation
- 045171550
- MA holder
- ALFASIGMA S.P.A.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Reumaflex 50 mg/ml soluzione iniettabile, siringa preriempita
PRD11003609 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 2.9 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AX03 — -
- Marketing authorisation
- 045171446
- MA holder
- ALFASIGMA S.P.A.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Giannina Gaslini Institute For Scientific Hospitalization And Care
- Sponsor organisation
- Giannina Gaslini Institute For Scientific Hospitalization And Care
- Address
- Via Gerolamo Gaslini 5
- City
- Genoa
- Postcode
- 16147
- Country
- Italy
Scientific contact point
- Organisation
- Giannina Gaslini Institute For Scientific Hospitalization And Care
- Contact name
- Alessandro Consolaro
Public contact point
- Organisation
- Giannina Gaslini Institute For Scientific Hospitalization And Care
- Contact name
- Alessandro Consolaro
Locations
1 EU/EEA country · 20 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 260 | 20 |
| Rest of world | — | 0 | — |
Investigational sites
Azienda USL IRCCS Di Reggio Emilia
Unità trial clinici di reumatologia, Viale Risorgimento 80, 42123, Reggio Emilia
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Salute della Donna, del Bambino e dell'Adolescente, Via Pietro Albertoni 15, 40138, Bologna
Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo
Scienze della Riproduzione e dello Sviluppo, Via Dell' Istria 65/1, 34137, Trieste
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Unita' di Immunologia e Reumatologia Pediatrica, Piazzale Spedali Civili 1, 25123, Brescia
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Clinica Pediatrica, Via Santa Sofia 78, 95123, Catania
Azienda Unita Sanitaria Locale Della Romagna
Dipartimento Salute Donna, Infanzia ed età evolutiva, Viale Vincenzo Randi 5, 48121, Ravenna
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
UOC Pediatria a Media Intensità di Cure, Via Della Commenda 12, 20122, Milan
IRCCS Istituto Giannina Gaslini
UOC Reumatologia e Malattie Autoinfiammatorie, Via Gerolamo Gaslini 5, 16147, Genoa
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Dipartimento di Pediatria F.Fede, Piazza Luigi Miraglia 2, 80138, Naples
Ospedale Pediatrico Bambino Gesu
Reumatologia, Piazza Di Sant'onofrio 4, 00165, Rome
Azienda Ospedaliera Universitaria Meyer IRCCS
Dipartimento di Pediatria, Viale Gaetano Pieraccini 24, 50139, Florence
Azienda Sanitaria Locale 2 Lanciano Vasto Chieti
Dipartimento di Pediatria, Via Dei Vestini Snc, 66100, Chieti
Ospedale Santa Chiara
Pediatria, Via Roma 67, 56126, Pisa
ARNAS Civico Di Cristina Benfratelli
Dipartimento Universitario, Piazza Nicola Leotta 4, 90127, Palermo
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Dip.to di Scienze Pediatriche e dell'Adolescenza, Piazza Polonia 94, 10126, Turin
Azienda Ospedaliera Universitaria Federico II Di Napoli
Dipartimento di Pediatria, Via Sergio Pansini 5, 80131, Naples
Asst Centro Specialistico Ortopedico Traumatologico Gaetano Pini Cto
Divisione di Reumatologia, Piazza Cardinale Andrea Ferrari 1, 20122, Milan
Ospedale Vito Fazzi Lecce
UOSD Reumatologia e Immunologia Pediatrica, Piazza Filippo Muratore 1, 73100, Lecce
Azienda Ospedaliero Universitaria Renato Dulbecco
UOC Pediatria Specialistica e Malattie Rare, Viale Europa, 88100, Catanzaro
Ospedale Pediatrico Giovanni XXIII, AOU Consorziale Policlinico di Bari
UOC Pediatria, Via Giovanni Amendola 207, 70126, Bari
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2024-09-04 | 2025-05-29 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2023-505051-43-00 | 5 |
| Recruitment arrangements (for publication) | K1_placeholder | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parent | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF post pubertal patient | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pre pubertal patient | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_Enbrel | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_Reumaflex | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ENG 2023-505051-43-00 | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ITA_2023-505051-43-00 | 2 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-10 | Italy | Acceptable 2024-07-25
|
2024-09-04 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-12-13 | Italy | Acceptable 2024-07-25
|
2024-12-13 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-07-17 | Italy | Acceptable 2025-09-29
|
2025-09-30 |