Clinical Trials Register

Summary
EudraCT Number:	2011-001243-67
Sponsor's Protocol Code Number:	CAIN457A2208
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-04-27
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

Germany - PEI

A.2

EudraCT number

2011-001243-67

A.3

Full title of the trial

An open-label proof-of-concept study with a double-masked, dose-ranging component to assess the effects of AIN457 in patients with noninfectious uveitis

A.3.1

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

Safety and effectiveness of AIN457 in the treatment of patients with noninfectious uveitis

A.3.2

Name or abbreviated title of the trial where available

A2208

A.4.1

Sponsor's protocol code number

CAIN457A2208

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00685399

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma GmbH
B.5.2	Functional name of contact point	Medical Competence Center
B.5.3	Address:
B.5.3.1	Street Address	Roonstrasse 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49180223 23 00
B.5.5	Fax number	+49911273 12160
B.5.6	E-mail	infoservice.novartis@novartis.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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMEA/OD/060/09
D.3 Description of the IMP
D.3.1	Product name	Secukinumab
D.3.2	Product code	AIN457
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	AIN457
D.3.9.4	EV Substance Code	SUB14228MIG
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

Intermediate, posterior or pan-uveitis of noninfectious origin

E.1.1.1

Medical condition in easily understood language

Inflammation of the eye involving the uveal layer

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10033687
E.1.2	Term	Panuveitis
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10036370
E.1.2	Term	Posterior uveitis
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10022557
E.1.2	Term	Intermediate uveitis
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

This study has 6 cohorts of patients with noninfectious uveitis. The recruitments for cohorts 1 to 5 are closed. Therefore, patients in Germany can only be recruited in cohort 6 which purpose is to assess the safety and tolerability of intravenous AIN457 in patients with uveitis. Patients in Cohort 6 may continue to be retreated, if eligible, in Cohort 4, thru 1 year past the LPLV for Cohort 6.

E.2.2

Secondary objectives of the trial

To determine whether doses of AIN457 of 300 mg sub-cutaneous administered every two weeks, 10 mg/kg IV every two weeks or 30 mg/kg IV every 4 weeks with or without a short course of corticosteroids are able to induce a clinically significant reduction in the severity of uveitis in the study eye at the end of an 8 week treatment period.
To determine whether doses of AIN457 of 300 mg sub-cutaneous administered every two weeks, 10 mg/kg IV every two weeks or 30 mg/kg IV every 4 weeks with or without a short course of corticosteroids are able to induce a sustained remission of uveitis in both eyes at the end of an 8 week treatment period.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

This study has 6 cohorts of patients with noninfectious uveitis. The recruitments for cohorts 1 to 5 are closed. Therefore, patients in Germany can only be recruited in cohort 6 for which principal inclusion criteria are:
1.Male and female subjects age 18 to 75 (inclusive) years of age
2.All female subjects must have negative pregnancy test results at screening and just before each dose
3.Male subjects must agree to use simultaneously two acceptable methods of contraception for the entire duration of the study, up to the study completion visit, unless they have undergone a vasectomy more thans six months prior to first dosing. A vasectomy must be supported with clinical documentation made available to the sponsor and/or Principal Investigator and noted in the Relevant Medical History/Current Medical Conditions sections of the CRF.
4.Able to communicate well with the investigator, to understand and comply with the requirements of the study.
5.Understand and sign the written informed consent.
6.Patients with noninfectious uveitis requiring systemic immunosuppression with prednisone or with agents other than or in addition to prednisone. The forms of uveitis include but are not limited to Behcet`s disease, Vogt-Koyanagi-Harada disease, sarcoidosis, anterior uveitis, intermediate uveitis or pars planitis, posterior uveitis, and panuveitis.
7.At the screening visit and baseline visit, the vitreous haze score must be +1 or worse in the study eye.

E.4

Principal exclusion criteria

This study has 6 cohorts of patients with noninfectious uveitis. The recruitments for cohorts 1 to 5 are closed. Therefore, patients in Germany can only be recruited in cohort 6 for which principal exclusion criteria are:
1.Participation in any other clinical investigation within 4 weeks prior to Day 1 (or longer if required by local regulation), and for any other limitation of participation based on local regulations.
2.Any concurrent medical condition unrelated to uveitis that requires immunosuppressive or immunomodulatory therapy or that may be exacerbated by immunosuppressive therapies.
3.Body weight greater than 120 kg.
4.Systemic or extraocular disease that would contraindicate long-term immunosuppression, especially infectious diseases such as any active infection within 2 weeks of screening with the exception of the common cold, a history of an infectious disease that can spontaneously re-emerge or that are impossible to completely cure such as tuberculosis, histoplasmosis, toxoplasmosis, malaria, viral hepatitis and HIV/AIDS, a history of on-going, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by either a positive PPD skin test or a positive QuantiFERON TB-Gold test. Patients with evidence of latent tuberculosis may enter the trial after evaluation by an appropriate specialist and after sufficient treatment has been initiated according to local regulations or standard of care.
5.Donation or loss of 400 ml or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation.
6.Significant illness within two weeks prior to dosing.
7.History of clinically significant adverse events to vaccines or other "antibodies" drugs.
8.History of lymphoproliferative disease or any known malignancy or history of malignancy within the past 5 years of any organ system, treated or untreated, whether or not there is evidence of local recurrence or metastases.
9.Uveitis that is so severe that, in the investigator`s judgment, it is too risky to test an experimental drug
10.Uveitis with an underlying diagnosis that is uncertain and which would reasonably include a disease for which immunosuppression would be contraindicated or for which immunosuppression is not proven to be beneficial
11.Forms of uveitis that may spontaneously resolve such as acute multifocal placoid pigment epitheliopathy or multiple evanescent white dot syndrome.
12. Oral non-steroidal immunosuppressive drugs are allowed up to the baseline day as long the dose has not changed during the 3 weeks prior to baseline.
13. Any systemic immunosuppressive antibodies given intravenously or subcutaneously
within 4 months prior to Day 1 such as infliximab, daclizumab, etanercept, or
adalimumab, except for Raptiva (efalizumab) and Rituxan (rituximab) which are excluded
for 12 months prior to Day 1.
14. Any previous AIN457 treatment.
15. Periocular or intra-vitreal drugs (e.g., corticosteroids) administered to the study eye within three months prior to Day 1.
16. A Retisert® implant in the study eye within the last 3 years.
17. Use of antibiotic treatment over the 4 weeks prior to screening that cannot safely be discontinued at the screening visit or that is given between the screening visit and the baseline visit.
18. Topical ocular steroid therapy greater than the equivalent of Prednisolone acetate 1% every hour while awake within 1 week of Day 1.
19. Ocular surgery in the study eye within the last 4 months except for a diagnostic vitreous or aqueous tap with a small-gauge needle.

E.5 End points

E.5.1

Primary end point(s)

This study has 6 cohorts of patients with noninfectious uveitis. The recruitments for cohorts 1 to 5 are closed. Therefore, patients in Germany can only be recruited in cohort 6 for which primary end points are:
The primary statistical analysis will be based on the percentage of patients in response and complete response (remission). A patient is considered a responder if meeting at least one of the
following criteria:
- Decrease in vitreous haze by 2 steps or more OR reduction of vitreous haze to 0.5 or 0.0 without an increase in daily prednisone dose or topical corticosteroids dose compared to baseline week 1
- Reduction in daily prednisone dose to 10 mg/day or less for those patients on more than 20 mg/day of prednisone during baseline week 1 OR to 0 mg/day for those patients on less than or equal to 20 mg/day of
prednisone during baseline week 1 OR reduction in daily topical corticosteroid dose to 0 for patients only on topical corticosteroids during baseline week 1 without initiation of oral prednisone without any
worsening of uveitis.

"Without any worsening of uveitis" is defined as no increase in vitreous haze and no increase in anterior chamber inflammation other then from 0 to +0.5 and less than 5-letter decrease in visual acuity.

Uveitis wii be considered in complete response (remission) if, both eyes, cells in the anterior chamber and vitreous haze scores are 0.5 or 0.0 for a minimum of 1 week and the patient is not taking any immunosuppressive therapy other than AIN457.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 week

E.5.2

Secondary end point(s)

Secondary endpoints include the percent of time during the 8-week treatment period that the patient shows a response to study medication and the time to first response.

E.5.2.1

Timepoint(s) of evaluation of this end point

8 weeks

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised