Clinical Trials Register

Summary
EudraCT Number:	2009-014835-19
Sponsor's Protocol Code Number:	CAIN457C2301
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-05-18
Trial results	View 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

2009-014835-19

A.3

Full title of the trial

A 24-week multicenter, randomized, double-masked, placebo controlled, dose-ranging phase III study of AIN457 versus placebo for maintaining uveitis suppression when reducing systemic immunosuppression in patients with quiescent, non-infectious intermediate, posterior or panuveitis (ENDURE Study)

A.3.2

Name or abbreviated title of the trial where available

ENDURE, C2301

A.4.1

Sponsor's protocol code number

CAIN457C2301

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	NOVARTIS FARMA
B.1.3.4	Country	Italy
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
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.3.2	Product code	AIN457
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	AIN457
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	150
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)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
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	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	anticorpo monoclonale umano anti-Interleuchina 17A della classe delle IgG1/kappa

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

quiescent, non-infectious intermediate, posterior or panuveitis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10033687
E.1.2	Term	Panuveitis

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 three dose regimens of subcutaneous AIN457 compared to placebo for maintaining the suppression of intraocular inflammation and the prevention of an active intermediate, posterior or panuveitis recurrence during the withdrawal of concomitant immunosuppressive therapy in adults with quiescent, non-infectious, uveitis affecting the posterior segment desiring to wean from the standard-of-care systemic immunosuppressive therapy required to control their ocular inflammatory disease.

E.2.2

Secondary objectives of the trial

• Key secondary objective 1: To determine if treatment with subcutaneous AIN457 can reduce or eliminate the need for standard-of-care immunosuppressive medications • Key secondary objective 2: To determine if treatment with subcutaneous AIN457 can delay the time to recurrence of active intermediate, posterior, or panuveitis from baseline • To assess the safety of targeted IL-17 inhibition with AIN457 in patients with quiescent uveitis affecting the posterior segment requiring standard-of-care immunosuppression • To evaluate the effect of subcutaneous AIN457 on visual acuity and quality of life when used as an adjunctive immunomodulatory therapy to standard-of-care immunosuppressive treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female subjects ≥18 years of age; 2. Patients with quiescent chronic, non-infectious intermediate uveitis, posterior uveitis or
panuveitis as evidenced by <1+ anterior chamber cell grade and <1+ vitreous haze in both eyes for at least 6 weeks prior to screening;
3. Requirement for either of the following immunosuppressive therapies at any time within the past 3 months for the treatment or prevention of uveitis which must not have been
increased within the 6 weeks prior to screening: • Prednisone or equivalent ≥10 mg daily; • ≥1 periocular injection or ≥1 intravitreal corticosteroid injection (i.e. triamcinolone) in the study eye within the past 6 months (the last injection must not have been given 6 weeks prior to screening); • Treatment with either cyclosporine, tacrolimus,azathioprine, mycophenolate mofetil,mycophenolic acid, methotrexate as monotherapy or in combination with or without
steroids. (Patients treated with chlorambucil or cyclophosphamide within the past 5 years are ineligible for the study); • Patients not meeting the above specified criteria for immunosuppressive therapies
are eligible for enrollment if they are intolerant to systemic immunosuppressive therapy as determined by the study investigator;
4. Patients must be willing to be weaned from their current systemic immunosuppressive therapy; 5. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed.

E.4

Principal exclusion criteria

Ocular concomitant conditions/disease. 1. Patients should be excluded: Uveitis secondary to Beh�et’s disease; Anterior uveitis; Any intermediate uveitis, posterior uveitis or panuveitis in which the manifestation(s) of the active intraocular inflammatory disease may spontaneously resolve without treatment; Any intermediate uveitis, posterior uveitis or panuveitis in which the patients history or the clinical manifestations of the disease are not characterized by the presence of either anterior chamber cells or vitritis such as the white dot retino-choroidopathies, acute zonal occult outer retinopathy. 2. Patients with active, non-infectious intermediate, posterior or panuveitis in one or both eyes. 3. Patients receiving or that may require corticosteroids ≥1 mg/kg/day to maintain quiescence of their intraocular inflammation. 4. Patients with infectious uveitis or uveitis of an underlying diagnosis that is uncertain and would reasonably include a disease for which immunosuppression would be contraindicated.
Ocular treatments. 5.Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening. 6. Treatment with fluocinolone acetonide implant (Retisert) in the study eye within the last 3 years, or dexamethasone intravitreal implant and any other investigational corticosteroid implants in the study eye within the last 6 months. 7. Intraocular surgery or laser photocoagulation in the study eye within the last 6 weeks prior
to screening except for a diagnostic vitreous or aqueous tap with a small-gauge needle. 8. Planned elective ocular surgery during the study. 9. Ocular disease that would interfere with ocular evaluations. 10. Current use of or likely need for systemic medications known to be toxic to the lens, retina, or optic nerve
Systemic conditions or treatments. 11. Any previous treatment with AIN457. 12. Any systemic biologic therapy given intravenously or subcutaneously within 3 months prior to screening.. 13. Any prior treatment with systemic alkylating agents within the past 5 years prior to screening. 14. Treatment with any live or live-attenuated vaccine within 2 months prior to screening. 15. Active systemic infections during the last two weeks prior to screening. 16. Underlying metabolic, hematologic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at an unacceptable risk for participation in an immunomodulatory therapy. 17. Systemic or extraocular disease that would contraindicate long-term immunosuppression, especially infectious diseases. 18. History of lymphoproliferative disease or any known malignancy or history of malignancy within the past 5 years of any organ system. 20. Any medical or psychiatric condition which, in the investigator’s opinion would preclude the participant from adhering to the protocol or completing the study per protocol.
Compliance/Administrative. 21. Inability or unwillingness to undergo repeated subcutaneous injections. 22. Inability or unwillingness to receive treatment with oral corticosteroids if recommended by the study investigator. 23. Participation in any other interventional study within 4 weeks prior to screening, and for any other limitation of participation based on local regulations. 24. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum pregnancy test (hCG>5mIU/ml) 25. Women of childbearing potential, defined as in Protocol section 4.2

E.5 End points

E.5.1

Primary end point(s)

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

Yes

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

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

E.8.7

Trial has a data monitoring committee

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

Dopo il completamento del trattamento core i pazienti entreranno nello studio di estensione CAIN457C2301E1 per un trattamento addizionale di 26 settimane oppure un periodo di follow-up di 12 settimane senza trattamento

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	20
F.4.2	For a multinational trial
F.4.2.1	In the EEA	125
F.4.2.2	In the whole clinical trial	232

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

2010-07-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-05-13

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2011-03-28

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