Clinical Trials Register

Summary
EudraCT Number:	2018-000681-10
Sponsor's Protocol Code Number:	I1F-MC-RHCG
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-24
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-000681-10

A.3

Full title of the trial

Multicenter, Open-label, Efficacy, Safety, Tolerability, and Pharmacokinetic Study of Subcutaneous Ixekizumab with Adalimumab Reference Arm, in Children with Juvenile Idiopathic Arthritis Subtypes of Enthesitis-related Arthritis (Including Juvenile-Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis

Studio multicentrico, in aperto, per la valutazione dell'efficacia, della sicurezza, della tollerabilità e della farmacocinetica di Ixekizumab (somministrato per via sottocutanea) con braccio di trattamento Adalimumab come riferimento, in pazienti pediatrici affetti da artrite idiopatica giovanile, nei sottotipi di artrite associata ad entesite (incluso spondilite anchilosante ad esordio giovanile) e artrite psoriasica giovanile.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

An Ixekizumab study with Adalimumab reference arm in children and young adults with Juvenile Idiopathic Arthritis Subtypes of Enthesitis-related Arthritis

Un studio dell'Ixekizumab con braccio di trattamento Adalimumab come riferimento in bambini e giovani adulti affetti da artrite idiopatica giovanile, nei sottotipi di artrite associata ad entesite(incluso spondilite anchilosante ad esordio giovanile) e artrite psoriasica giovanile.

A.3.2

Name or abbreviated title of the trial where available

TALZ

A.4.1

Sponsor's protocol code number

I1F-MC-RHCG

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/280/2019

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ELI LILLY & COMPANY, LILLY CORPORATE CENTER
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Eli Lilly and Company
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Eli Lilly
B.5.2	Functional name of contact point	Clinical Trial Registry Office
B.5.3	Address:
B.5.3.1	Street Address	Lilly Corporate Center, DC 1526
B.5.3.2	Town/ city	Indianapolis
B.5.3.3	Post code	46285
B.5.3.4	Country	United States
B.5.4	Telephone number	0000000000
B.5.5	Fax number	0000000000
B.5.6	E-mail	EU_Lilly_Clinical_Trials@lilly.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Taltz (80 mg solution for injection in pre-filled syringe)
D.2.1.1.2	Name of the Marketing Authorisation holder	ELI LILLY NEDERLAND B.V.
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ixekizumab
D.3.2	Product code	[TALTZ]
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ixekizumab
D.3.9.2	Current sponsor code	LY243921
D.3.9.4	EV Substance Code	SUB176389
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Humira
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Ltd
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Humira
D.3.2	Product code	[L04AB04]
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Adalimumab
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	HUMIRA
D.3.9.4	EV Substance Code	SUB20016
D.3.10	Strength
D.3.10.1	Concentration unit	1X 100 milligrams/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Juvenile Idiopathic Arthritis subtypes of enthesitis-related arthritis (including juvenile-onset ankylosing spondylitis) and juvenile psoriatic arthritis

Sottotipi di artrite associata ad entesite, ERA (incluso spondilite anchilosante ad esordio giovanile SpA-ERA) e artrite psoriasica giovanile, JPsA

artrite idiopatica giovanile (Juvenile Idiopathic Arthritis) = AIG (JIA)
sottotipi di artrite associata ad entesite (Subtypes of Enthesitis-related Arthritis) = ERA
artrite psoriasica giovanile (Juvenile Psoriatic Arthritis) = JPsA
spondilite anchilosante ad esordio giovanile (Juvenile-Onset Ankylosing Spondylitis) = SpA-ERA

E.1.1.1

Medical condition in easily understood language

Childhood Arthritis

Artrite giovanile

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of ixekizumab in children with JIA subtypes of ERA (including JoAS) and JPsA based on the JIA American College of Rheumatology (ACR) 30 response

Valutare l’efficacia di ixekizumab nei bambini affetti dai sottotipi di AIG ERA (inclusa JoAS) e APsG, sulla base della risposta ACR 30 (American College of Rheumatology) per AIG

E.2.2

Secondary objectives of the trial

1. To evaluate the efficacy of ixekizumab in children with JIA subtypes of ERA (including JoAS) and JPsA based on the other clinical responses, disease activity and physical function measures
2. To evaluate the efficacy of adalimumab (reference arm) in children with JIA subtypes of ERA (including JoAS) and JPsA based on JIA ACR 30 and the other clinical responses, disease activity and physical function measures
3. To characterize ixekizumab pharmacokinetics (PK) in children with JIA subtypes of ERA (including JoAS) and JPsA
4. To evaluate the potential development of antiixekizumab antibodies and their impact on the efficacy and safety of ixekizumab in children with JIA subtypes of ERA (including JoAS) and JPsA
5. Describe the safety of ixekizumab in patients with JIA subtypes of ERA (including JoAS) and JPsA

1. Valutare l’efficacia di ixekizumab nei bambini affetti dai sottotipi di AIG ERA (inclusa JoAS) e APsG, sulla base di altre risposte cliniche, dell’attività di malattia e delle misure di funzionalità fisica
2. Valutare l’efficacia di adalimumab (braccio di riferimento) nei bambini affetti dai sottotipi di AIG ERA (inclusa JoAS) e APsG, sulla base della risposta ACR 30 per AIG e delle altre risposte cliniche, dell’attività di malattia e delle misure di funzionalità fisica
3. Caratterizzare la farmacocinetica (PK) di ixekizumab nei bambini affetti dai sottotipi di AIG ERA (inclusa JoAS) e APsG
4. Valutare il potenziale sviluppo di anticorpi anti-ixekizumab e il loro impatto
sull’efficacia e sulla sicurezza di ixekizumab nei bambini affetti dai sottotipi di AIG ERA (inclusa JoAS) e APsG
5. Descrivere la sicurezza di ixekizumab nei pazienti affetti dai sottotipi di AIG ERA (inclusa JoAS) e APsG

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants must have active juvenile idiopathic arthritis (categories of enthesitis related arthritis or juvenile psoriatic arthritis)
Participants must have weight of at least 10 kilograms (Kg), age starting at 2 years for participants with juvenile psoriatic arthritis and starting at 6 years for participants with enthesitis related arthritis
Participants must have all immunizations up-to-date in agreement with current immunization guidelines, in the opinion of the investigator

I partecipanti devono soffrire di artrite idiopatica giovanile artrite associata a entesite o artrite psoriasica giovanile)
I partecipanti devono pesare almeno 10 chilogrammi (kg), avere un’età dai 2 anni se affetti da artrite psoriasica giovanile e dai 6 anni se affetti da artrite associata a entesite
I partecipanti devono aver ricevuto tutte le vaccinazioni previste dalle attuali linee guida sull’immunizzazione, a giudizio dello sperimentatore

E.4

Principal exclusion criteria

Participants must not have active or history of inflammatory bowel disease
Participants must not have active uveitis
Participants must not have active or latent tuberculosis
Participants must not have an active infection
Participants must not have concurrent use of biologic agents for the treatment of the juvenile idiopathic arthritis

I partecipanti non devono avere un’anamnesi di malattia infiammatoria intestinale o soffrire di malattia infiammatoria intestinale in fase attiva
I partecipanti non devono soffrire di uveite in fase attiva
I partecipanti non devono soffrire di tubercolosi in fase attiva o latente
I partecipanti non devono avere un’infezione in atto

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients meeting the JIA ACR 30 response criteria at Week 16

Percentuale di pazienti che rientrano nei criteri della risposta stabilita dall'ACR 30 (American College of Rheumatology) per AIG alla settimana 16.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 16

Settimana 16

E.5.2

Secondary end point(s)

- Percentage of patients meeting the JIA ACR 30/50/70/90/100 response criteria
- Changes from baseline in each of the 6 individual components of the JIA ACR core set variables
- Change from baseline in Psoriasis Area and Severity Index (PASI) for JPsA patients with at least 3% Body Surface Area (BSA) at baseline
- Change from baseline in Leeds Enthesitis Index (LEI) for patients with enthesitis at baseline
- Proportion of patients with disease flare (flare defined as worsening of =30% from baseline in at
least 3 of the 6 JIA ACR core set criteria and an improvement of =30% in no more than 1 of the
criteria)
- Trough concentrations of ixekizumab in patients with JIA subtypes of ERA (including JoAS) and JPsA at Week 16
- Percentage of patients with anti-ixekizumab antibodies
- Adverse events (AEs) including serious adverse
events (SAEs)
- Safety parameters including but not limited to infections, injection site reactions, and laboratory
data including B-, T-cell, and natural killer (NK)- cell levels, white blood cell (WBC) count, red
blood cell (RBC) count, alanine aminotransferase (ALT), aspartate aminotransferase (AST)

- Percentuale di pazienti che soddisfano i criteri della risposta ACR 30/50/70/90/100 per AIG
-Variazione rispetto al basale di ognuna delle 6 singole variabili fondamentali che compongono la risposta ACR per AIG
-Variazione rispetto al basale dell’indice PASI (Psoriasis Area and Severity Index) per i pazienti affetti da APsG con un coinvolgimento della superficie corporea (BSA) di almeno il 3% al basale
-Variazione rispetto al basale dell’indice LEI (Leeds Enthesitis Index) per i pazienti con entesite al basale
-Percentuale di pazienti con una riacutizzazione della malattia (dove con “riacutizzazione” si intende un peggioramento =30%, rispetto al basale, di almeno 3 dei 6 criteri fondamentali della risposta ACR per AIG e un miglioramento =30% di non più di 1 criterio)
-Concentrazione minima di ixekizumab nei pazienti affetti dai sottotipi di AIG ERA (inclusa JoAS) e APsG alla settimana 16
-Percentuale di pazienti con anticorpi anti-ixekizumab
-Eventi avversi (AE) inclusi gli eventi avversi seri (SAE)
-Parametri di sicurezza inclusi, in via non esaustiva, infezioni, reazioni nel sito di iniezione e dati di laboratorio tra cui livelli di linfociti B, T e natural killer (NK), numero di globuli bianchi, numero di globuli rossi, alanina aminotransferasi (ALT), aspartato aminotransferasi (AST).

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary outcomes will be assessed at each regular study visit (every 3 months)

Gli outcome secondari saranno valutati in occasione di ciascuna visita regolare prevista dallo studio (ogni 3 mesi)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tollerabilità

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Denmark

France

Germany

Italy

Netherlands

Spain

Switzerland

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients 2-18 years old

pazienti dai 2 ai 18 anni di età

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

100

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients who complete the OLT and OLE periods of this study may be eligible to participate in an open-label LTE study (Study RHCY) if enrollment criteria for the LTE are met.

I pazienti che completano i periodi OLT e OLE dello studio potranno essere eleggibili per la partecipazione allo studio di estensione in aperto a lungo termine (LTE) (studio RHCY), nel caso in cui vengano soddisfatti i criteri di arruolamento per la LTE

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-12-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-11-23

P. End of Trial
P.	End of Trial Status	Ongoing

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