Clinical trial • Phase III • Musculoskeletal|Dermatology|Immunology

USTEKINUMAB for Juvenile psoriatic arthritis

Phase III trial of USTEKINUMAB for Juvenile psoriatic arthritis.

Overview

Trial Therapeutic Area
Musculoskeletal|Dermatology|Immunology
Trial Disease
Juvenile psoriatic arthritis
Trial Stage
Phase III
Drug Modality
Monoclonal antibody
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
08-05-2024
First CTIS Authorization Date
17-07-2024

Trial design

open-label, cohort 1: ustekinumab (subcutaneous; products: stelara 45 mg and stelara 90 mg solution for injection in pre-filled syringe; dosing interval referenced as 12-week interval for pk assessments). cohort 2: guselkumab (subcutaneous; products: guselkumab 100 mg/ml or guselkumab formulations; dosing intervals referenced as 4- or 8-week intervals for pk assessments).-controlled Phase III trial across 24 sites in Denmark, Italy, Netherlands and others.

Open Label
Yes
Comparator
Cohort 1: Ustekinumab (subcutaneous; products: STELARA 45 mg and STELARA 90 mg solution for injection in pre-filled syringe; dosing interval referenced as 12-week interval for PK assessments). Cohort 2: Guselkumab (subcutaneous; products: Guselkumab 100 mg/mL or guselkumab formulations; dosing intervals referenced as 4- or 8-week intervals for PK assessments).
Target Sample Size
28
Trial Duration For Participant
476

Eligibility

Recruits 28 paediatric patients.

Vulnerable Population
The trial enrols pediatric participants aged ≥5 to <18 years (vulnerable population selected). Consent and assent handling includes age-specific informed consent and assent documents: parental/legal guardian consent required; assent from children/adolescents (documents and assent forms available for ages including 6-12 and 13-17). There are specific ICF/assent and related materials (child, adolescent, parental/legal guardian, withdrawal, pregnant partner, turning 18) provided in multiple country-language versions (examples in French, Spanish, German, Polish indicated in the submitted documents).

Inclusion criteria

  • {"criterion_text":"- ≥5 to <18 years of age, inclusive.\n- Diagnosis of jPsA by Vancouver inclusion criteria, with exclusion of ERA. Diagnosis made ≥3 months (ie. 90 days) prior to screening. Arthritis plus psoriasis, or arthritis plus ≥2 of the following: dactylitis, nail pits, family history of psoriasis in a first- or second-degree relative, psoriasis-like rash.\n- Active disease in ≥3 joints at screening and at Week 0 (defined as swelling or loss of motion with pain and/or tenderness). Swelling alone meets the criteria for an active arthritic joint. In the absence of swelling, loss of motion with pain or tenderness or both pain and tenderness meet the criteria for an active arthritic joint\n- Have active disease despite previous non-biologic DMARD and/or NSAID therapy: •\tNon-biologic DMARD therapy is defined as taking a non-biologic DMARD for at least 12 weeks or evidence of intolerance. •\tNSAID therapy is defined as taking an NSAID for at least 4 weeks or evidence of intolerance.\n- If previously treated with an anti-TNFα agent (such as adalimumab, etanercept, infliximab, golimumab [SC or IV], certolizumab pegol, or their respective biosimilars) or other biologic agents that are not included in the exclusion criteria, these agents should have been discontinued taking into consideration their elimination half-life, dosing frequency and acceptable clinical practice, before first study intervention administration (see Appendix 7 [Section 10.7] for Table 7 with the required minimal washout period for a specific prior treatment). Refer to Appendix 18 (Section 10.18.1) for country-specific requirements in France for the required minimum washout periods for Anti-TNFα agents."}

Exclusion criteria

  • {"criterion_text":"- Participants with enthesitis-related arthritis (ERA; see definition in Appendix 17 of the study protocol)\n- Taken any disallowed therapies as noted in Section 6.8, Concomitant Therapy within the timeframe specified before the planned first dose of study intervention.\n- If participants were non-responders to previously received IL-23 blockers including guselkumab, tildrakizumab (MK3222) and risankizumab (BI-655066). Prior non-response to an anti-TNFα inhibitor, an IL-17 inhibitor or a Janus kinase (JAK) inhibitor is not an exclusion. Participants who previously discontinued ustekinumab for intolerance or inadequate response may be enrolled into the guselkumab cohort. Patients who previously discontinued guselkumab due to intolerance may be enrolled into the ustekinumab cohort. Participants who previously discontinued tildrakizumab or risankizumab due to intolerance may be enrolled into either cohort.\n- Has other inflammatory disease that might confound the evaluation of benefit from ustekinumab or guselkumab therapy, including but not limited to moderate to severe inflammatory bowel disease, systemic lupus erythematosus, or Lyme disease.\n- Has active uveitis within 12 weeks prior to the first administration of study intervention."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Ustekinumab Steady-state trough concentrations and population PK model-predicted AUCss over a 12-week dosing interval at Week 28 by baseline age groups.","definition_or_measurement_approach":"Measurement: observed steady-state trough concentrations and population PK model-predicted AUCss over a 12-week dosing interval at Week 28, analysed by baseline age groups."}
  • {"endpoint_text":"- Ustekinumab ACR Pedi 30 response at Week 24.","definition_or_measurement_approach":"Measurement: proportion of participants achieving ACR Pedi 30 response at Week 24 according to American College of Rheumatology Pediatric criteria."}
  • {"endpoint_text":"- Guselkumab Steady-state trough concentrations and population PK model-predicted AUCss over a dosing interval (4 or 8 weeks) at Week 28 by baseline age groups.","definition_or_measurement_approach":"Measurement: observed steady-state trough concentrations and population PK model-predicted AUCss over a dosing interval (4 or 8 weeks) at Week 28, analysed by baseline age groups."}
  • {"endpoint_text":"- Guselkumab ACR Pedi 30 response at Week 24.","definition_or_measurement_approach":"Measurement: proportion of participants achieving ACR Pedi 30 response at Week 24 according to American College of Rheumatology Pediatric criteria."}

Secondary endpoints

  • {"endpoint_text":"- PK – Ustekinumab Steady-state trough concentrations and population PK model-predicted AUCss over a 12-week dosing interval at Week 52 by baseline age groups","definition_or_measurement_approach":"Measurement: observed steady-state trough concentrations and population PK model-predicted AUCss over a 12-week dosing interval at Week 52, by baseline age groups."}
  • {"endpoint_text":"- PK – Guselkumab Steady-state trough concentrations and population PK model-predicted AUCss over a dosing interval (4 or 8 weeks) at Week 52 by baseline age groups.","definition_or_measurement_approach":"Measurement: observed steady-state trough concentrations and population PK model-predicted AUCss over a dosing interval (4 or 8 weeks) at Week 52, by baseline age groups."}
  • {"endpoint_text":"- Efficacy – Ustekinumab ACR Pedi 30 response at Weeks 4, 8, 12, 16, and 52.","definition_or_measurement_approach":"Measurement: ACR Pedi 30 response assessed at specified weeks (4, 8, 12, 16, 52) per ACR Pedi criteria."}
  • {"endpoint_text":"- Efficacy – Ustekinumab ACR Pedi 50 and 70 responses at Weeks 4, 8, 12, 16, 24, and 52.","definition_or_measurement_approach":"Measurement: ACR Pedi 50 and ACR Pedi 70 responses assessed at specified weeks per ACR Pedi criteria."}
  • {"endpoint_text":"- Efficacy – Ustekinumab Time to response measured as time to achieving ACR Pedi 30 from baseline through Week 24.","definition_or_measurement_approach":"Measurement: time (in days/weeks) from baseline to first achievement of ACR Pedi 30 within Week 24."}
  • {"endpoint_text":"- Efficacy – Ustekinumab Change from baseline in cJADAS 10, JADAS 10, 27, and 71 at Weeks 4, 8, 12, 16, 24, and 52.","definition_or_measurement_approach":"Measurement: change from baseline in cJADAS and JADAS scores at specified weeks."}
  • {"endpoint_text":"- Efficacy – Ustekinumab Change from baseline in PASI score at Week 24 among the participants with ≥3% BSA psoriatic involvement and a PGA psoriasis score of ≥2 (mild) at baseline.","definition_or_measurement_approach":"Measurement: change from baseline in PASI score at Week 24 among participants meeting baseline psoriasis criteria (≥3% BSA and PGA ≥2)."}
  • {"endpoint_text":"- Efficacy – Guselkumab ACR Pedi 30 response at Weeks 4, 8, 12, 16, and 52.","definition_or_measurement_approach":"Measurement: ACR Pedi 30 response assessed at specified weeks for guselkumab cohort."}
  • {"endpoint_text":"- Efficacy – Guselkumab ACR Pedi 50 and 70 responses at Weeks 4, 8, 12, 16, 24, and 52.","definition_or_measurement_approach":"Measurement: ACR Pedi 50 and 70 responses at specified weeks for guselkumab cohort."}
  • {"endpoint_text":"- Efficacy – Guselkumab Time to response measured as time to achieving ACR Pedi 30 from baseline through Week 24.","definition_or_measurement_approach":"Measurement: time from baseline to first achievement of ACR Pedi 30 through Week 24."}
  • {"endpoint_text":"- Efficacy – Guselkumab Change from baseline in cJADAS 10, JADAS 10, 27, and 71 at Weeks 4, 8, 12, 16, 24, and 52.","definition_or_measurement_approach":"Measurement: change from baseline in cJADAS and JADAS scores at specified weeks for guselkumab cohort."}
  • {"endpoint_text":"- Efficacy – Guselkumab Change from baseline in PASI score at Week 24 among the participants with ≥3% BSA psoriatic involvement and a PGA psoriasis score of ≥2 (mild) at baseline.","definition_or_measurement_approach":"Measurement: change from baseline in PASI at Week 24 among participants meeting baseline psoriasis criteria."}
  • {"endpoint_text":"- Safety – Ustekinumab The occurrences and type of AEs, SAEs, and reasonably related AEs.","definition_or_measurement_approach":"Measurement: incidence and types of adverse events (AEs), serious adverse events (SAEs), and events deemed reasonably related to study drug through safety reporting."}
  • {"endpoint_text":"- Safety –Guselkumab The occurrences and type of AEs, SAEs, and reasonably related AEs.","definition_or_measurement_approach":"Measurement: incidence and types of AEs, SAEs, and reasonably related events for guselkumab cohort."}
  • {"endpoint_text":"- Immunogenicity – Ustekinumab The incidence of antibodies to ustekinumab/guselkumab (including peak titers) through Week 52 and Week 68.","definition_or_measurement_approach":"Measurement: incidence of anti-drug antibodies (including peak titers) through Weeks 52 and 68."}
  • {"endpoint_text":"- Immunogenicity –Guselkumab The incidence of antibodies to ustekinumab/guselkumab (including peak titers) through Week 52 and Week 68.","definition_or_measurement_approach":"Measurement: incidence of anti-drug antibodies (including peak titers) through Weeks 52 and 68 for guselkumab cohort."}

Recruitment

Planned Sample Size
28
Recruitment Window Months
49
Consent Approach
Informed consent is provided by the parent/legal guardian; assent obtained from children as appropriate (age-specific assent forms documented). Age-specific informed consent and subject information materials are provided (child, adolescent, parental/legal guardian, withdrawal, pregnant partner, 'turning 18' materials). Documents and ICF/assent versions are available in country/language-specific versions (examples submitted include French, Spanish, German, Polish).

Methods

  • Patient recruitment activities conducted by IQVIA Limited (role listed as 'Patient recruitment' in sponsor third-party duties).
  • Central laboratory and specialist vendor support (Labcorp Central Laboratory Services SARL / Labcorp Central Laboratory Services LP) and other vendor support for study operations as listed in third-party roles (no explicit public recruitment channels described in the submission).

Geography

Total Number Of Sites
24
Total Number Of Participants
28

Denmark

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
21-07-2024
Processing Time Days
59
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
Odense University Hospital
Department Name
HC Andersen Childrens Hospital
Principal Investigator Name
Anne Estmann
Principal Investigator Email
anne.estmann@rsyd.dk
Contact Person Name
Anne Estmann
Contact Person Email
anne.estmann@rsyd.dk
Site Name
Aarhus Universitetshospital
Department Name
Department of Pediatrics
Principal Investigator Name
Mia Glerup
Principal Investigator Email
miagleru@rm.dk
Contact Person Name
Mia Glerup
Contact Person Email
miagleru@rm.dk

Italy

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
22-07-2024
Processing Time Days
60
Number Of Sites
5
Number Of Participants
5

Sites

Site Name
Asst Centro Specialistico Ortopedico Traumatologico Gaetano Pini Cto
Department Name
UO Reumatologia Pediatrica
Principal Investigator Name
Achille Marino
Principal Investigator Email
achille.marino@asst-pini-cto.it
Contact Person Name
Achille Marino
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
UOC Pediatria
Principal Investigator Name
Giovanni Filocamo
Principal Investigator Email
giovanni.filocamo@policlinico.mi.it
Contact Person Name
Giovanni Filocamo
Site Name
Ospedale Pediatrico Bambino Gesu
Department Name
U.O. Reumatologia
Principal Investigator Name
Silvia Magni Manzoni
Principal Investigator Email
silvia.magnimanzoni@opbg.net
Contact Person Name
Silvia Magni Manzoni
Contact Person Email
silvia.magnimanzoni@opbg.net
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
Reumatologia Pediatrica
Principal Investigator Name
Marco Cattalini
Principal Investigator Email
marco.cattalini@unibs.it
Contact Person Name
Marco Cattalini
Contact Person Email
marco.cattalini@unibs.it
Site Name
IRCCS Istituto Giannina Gaslini
Department Name
UOC Reumatologia e Malattie Autoinfiammatorie
Principal Investigator Name
Silvia Rosina
Principal Investigator Email
silviarosina@gaslini.org
Contact Person Name
Silvia Rosina
Contact Person Email
silviarosina@gaslini.org

Netherlands

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
17-07-2024
Processing Time Days
55
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
rheumatology
Principal Investigator Name
Philomine van Pelt
Principal Investigator Email
p.vanpelt@erasmusmc.nl
Contact Person Name
Philomine van Pelt
Contact Person Email
p.vanpelt@erasmusmc.nl

France

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
17-07-2024
Processing Time Days
55
Number Of Sites
5
Number Of Participants
1

Sites

Site Name
Bicetre Hospital
Department Name
Pediatrcs
Principal Investigator Name
Linda ROSSI
Principal Investigator Email
linda.rossi@aphp.fr
Contact Person Name
Linda ROSSI
Contact Person Email
linda.rossi@aphp.fr
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Pediatrics
Principal Investigator Name
Alexandra DESDOITS
Principal Investigator Email
desdoits-a@chu-caen.fr
Contact Person Name
Alexandra DESDOITS
Contact Person Email
desdoits-a@chu-caen.fr
Site Name
CHRU De Nancy
Department Name
Pediatrics
Principal Investigator Name
Irene LEMELLE
Principal Investigator Email
i.lemelle@chru-nancy.fr
Contact Person Name
Irene LEMELLE
Contact Person Email
i.lemelle@chru-nancy.fr
Site Name
Hopital Des Enfants
Department Name
Pediatrics
Principal Investigator Name
Christine PAJOT
Principal Investigator Email
pajot.c@chu-toulouse.fr
Contact Person Name
Christine PAJOT
Contact Person Email
pajot.c@chu-toulouse.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Pediatrics
Principal Investigator Name
Diego URBINA
Principal Investigator Email
diego.urbina@ap-hm.fr
Contact Person Name
Diego URBINA
Contact Person Email
diego.urbina@ap-hm.fr

Germany

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
19-07-2024
Processing Time Days
57
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
Asklepios Klinik Sankt Augustin GmbH
Department Name
Pediatric department
Principal Investigator Name
Gerd Horneff
Principal Investigator Email
g.horneff@asklepios.com
Contact Person Name
Gerd Horneff
Contact Person Email
g.horneff@asklepios.com
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
SPZ Rheumatologie
Principal Investigator Name
Kirsten Minden
Principal Investigator Email
kirsten.minden@charite.de
Contact Person Name
Kirsten Minden
Contact Person Email
kirsten.minden@charite.de
Site Name
Schoen Klinik Hamburg Eilbek
Department Name
Rheumatology
Principal Investigator Name
Ivan Foeldvari
Principal Investigator Email
foeldvari@t-online.de
Contact Person Name
Ivan Foeldvari
Contact Person Email
foeldvari@t-online.de

Spain

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
17-07-2024
Processing Time Days
55
Number Of Sites
5
Number Of Participants
6

Sites

Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Raumatology
Principal Investigator Name
Antonio Mera Varela
Principal Investigator Email
antonio.mera.varela@sergas.es
Contact Person Name
Antonio Mera Varela
Contact Person Email
antonio.mera.varela@sergas.es
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Raumatology
Principal Investigator Name
Berta Paula Magallares Lopez
Principal Investigator Email
bmagallares@santpau.cat
Contact Person Name
Berta Paula Magallares Lopez
Contact Person Email
bmagallares@santpau.cat
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Principal Investigator Name
Mireia Lopez Corbeto
Principal Investigator Email
mireia.lopez@vallhebron.cat
Contact Person Name
Mireia Lopez Corbeto
Contact Person Email
mireia.lopez@vallhebron.cat
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Rheumatology
Principal Investigator Name
Lucia Lacruz Perez
Principal Investigator Email
lacruz_lucper@gva.es
Contact Person Name
Lucia Lacruz Perez
Contact Person Email
lacruz_lucper@gva.es
Site Name
Hospital General Universitario Reina Sofia
Department Name
Raumatology
Principal Investigator Name
Maria Rosa Roldan Molina
Principal Investigator Email
rosa.roldan@hotmail.es
Contact Person Name
Maria Rosa Roldan Molina
Contact Person Email
rosa.roldan@hotmail.es

Poland

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
17-07-2024
Processing Time Days
55
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi
Department Name
Oddział Kardiologii i Reumatologii dla Dzieci
Principal Investigator Name
Elżbieta Smolewska
Principal Investigator Email
e.smolewska@wp.pl
Contact Person Name
Elżbieta Smolewska
Contact Person Email
e.smolewska@wp.pl
Site Name
Centrum Zdrowia Dziecka I Rodziny Im. Jana Pawla II W Sosnowcu Sp. z o.o.
Department Name
Ośrodek Badań Klinicznych
Principal Investigator Name
Anna Gruenpeter
Principal Investigator Email
anna.gruenpeter@gmail.com
Contact Person Name
Anna Gruenpeter
Contact Person Email
anna.gruenpeter@gmail.com
Site Name
Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher
Department Name
Centrum Wsparcia Badań Klinicznych
Principal Investigator Name
Piotr Gietka
Principal Investigator Email
piotr.gietka@spartanska.pl
Contact Person Name
Piotr Gietka
Contact Person Email
piotr.gietka@spartanska.pl

Sponsor

Primary sponsor

Full Name
Janssen - Cilag International
Organisation Type
Pharmaceutical company
Country Of Registered Address
Belgium

Contract research organisations

Name
Eresearchtechnology Inc.
Responsibilities
eCoA, eLearning, Investigator Meeting, Custom Reports (as listed in sponsor duties)
Name
IQVIA Limited
Responsibilities
Multiple study support roles including patient recruitment (listed as 'Patient recruitment') and other listed duties
Name
Almac Clinical Technologies LLC
Responsibilities
Responsibilities listed under sponsor duties (code 3)
Name
Medidata Solutions Inc.
Responsibilities
Responsibilities listed under sponsor duties (code 7)

Third parties

  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: 4; contact zara.saeed@labcorp.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties: code 15; value: eCoA, eLearning, Investigator Meeting, Custom Reports","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties codes: 4; contact zara.saeed@labcorp.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties codes: 3; contact IRTHelp@almacgroup.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ancillare LP","duties_or_roles":"sponsorDuties: code 15; value: Ancillary supplies","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7; contact Matthew.RILEY@3ds.com","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1,12,15(value: Patient recruitment),2,5,6,8; contact eu_clinical_trials_information@iqvia.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"sponsorDuties codes: 4; contact srebarch@its.jnj.com","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
STELARA 90 mg solution for injection in pre-filled syringe / STELARA 45 mg solution for injection (ustekinumab)
Active Substance
USTEKINUMAB
Modality
Monoclonal antibody
Routes Of Administration
Subcutaneous use
Route
Subcutaneous
Authorisation Status
Marketing authorisation numbers present in submission (examples: EU/1/08/494/001 and EU/1/08/494/004 associated with STELARA products)
Dose Levels
45 mg; 90 mg (product strengths present in submission)
Frequency
Referenced in PK endpoints as 12-week dosing interval for ustekinumab
Maximum Dose
90 mg
Investigational Product Name
Guselkumab (Guselkumab - solution for injection in pre-filled syringe - 100 mg/mL)
Active Substance
GUSELKUMAB
Modality
Monoclonal antibody
Routes Of Administration
Subcutaneous use
Route
Subcutaneous
Authorisation Status
Product entries present (prodAuthStatus values in submission); product described as Guselkumab 100 mg/mL
Dose Levels
100 mg/mL formulation; dosing also referenced as mg/kg (maxTotalDoseAmount 1.3 mg/kg in one product entry)
Frequency
Referenced in PK endpoints as dosing interval of 4 or 8 weeks for guselkumab
Maximum Dose
100 mg/mL (product); 1.3 mg/kg (as indicated in one product entry)

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