Clinical Trials Register

Summary
EudraCT Number:	2011-001595-19
Sponsor's Protocol Code Number:	32-007
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-09-12
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

Austria - BASG

A.2

EudraCT number

2011-001595-19

A.3

Full title of the trial

A Phase III, Multinational, Multicenter, Randomized, Double-Masked, Study Assessing the Safety and Efficacy of Intravitreal Injections of DE-109 (three doses) for the Treatment of active, Non-Infectious Uveitis of the Posterior Segment of the eye

A.3.1

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

A study to see how safe and how well an investigational study drug will work to treat active non-infectious posterior, intermediate or pan-uveitis.

A.3.2

Name or abbreviated title of the trial where available

n/a

A.4.1

Sponsor's protocol code number

32-007

A.5.4

Other Identifiers

Name:

n/a

Number:

n/a

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	SANTEN INCORPORATED
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	SANTEN INCORPORATED
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	SANTEN INCORPORATED
B.5.2	Functional name of contact point	Crystal Browning
B.5.3	Address:
B.5.3.1	Street Address	2100 Powell Street, 16th. Floor
B.5.3.2	Town/ city	Emeryville
B.5.3.3	Post code	CA 94608
B.5.3.4	Country	United States
B.5.4	Telephone number	+1415268 9010
B.5.5	Fax number	+1510655 5687
B.5.6	E-mail	CBrowning@Santeninc.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	DE-109
D.3.2	Product code	DE-109
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sirolimus
D.3.9.1	CAS number	53123-88-9
D.3.9.2	Current sponsor code	DE-109
D.3.9.3	Other descriptive name	RAPA
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	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.3.1	Product name	DE-109
D.3.2	Product code	DE-109
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sirolimus
D.3.9.1	CAS number	53123-88-9
D.3.9.2	Current sponsor code	DE-109
D.3.9.3	Other descriptive name	RAPA
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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: 3
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.3.1	Product name	DE-109
D.3.2	Product code	DE-109
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sirolimus
D.3.9.1	CAS number	53123-88-9
D.3.9.2	Current sponsor code	DE-109
D.3.9.3	Other descriptive name	RAPA
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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

Uveitis of the Posterior Segment of the Eye.

E.1.1.1

Medical condition in easily understood language

Active non-infectious posterior, intermediate or pan-uveitis.

E.1.1.2

Therapeutic area

Body processes [G] - Ocular Physiological Phenomena [G14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10036370
E.1.2	Term	Posterior uveitis
E.1.2	System Organ Class	100000004862

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

To evaluate the safety and efficacy of intravitreal injection of 440 μg DE-
109 as compared with 44 μg DE-109 for the treatment of active, noninfectious uveitis of the posterior segment of the eye.

E.2.2

Secondary objectives of the trial

To evaluate the safety of intravitreal injection of 880 μg DE-109 as
compared to 44 μg DE-109 for the treatment of active, non-infectious
uveitis of the posterior segment of the eye.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Ability to give informed consent and attend all study visits
2. Males or females greater than or equal to 18 years of age
3. Have diagnosis of active uveitis of the posterior segment determined
by the Investigator to be noninfectious based on the subject's medical
history, history of present illness, ocular examination, review of
systems, physical examination, and any relevant, pertinent laboratory
evaluations. If an anterior component is present, it must be less than the
posterior component
4. Have active uveitis defined as a >1+ (excluding 1+) VH score
(modified SUN scale) in the study eye
5. Best-corrected ETDRS visual acuity letter score of 19 letters or more
(20/400 Snellen equivalent or better) in study eye
6. Female participants of childbearing potential must not be pregnant or
breast-feeding, have a negative pregnancy test at screening and must be
willing to undergo pregnancy tests throughout the study
7. Both female participants of childbearing potential and male
participants able to father children must have (or have a partner who
has) had a hysterectomy or vasectomy, must abstain from intercourse or
must agree to practice acceptable methods of contraception throughout
the course of the study
8. Subjects must have vision ≥ 20/200 in the non-study eye

E.4

Principal exclusion criteria

Ocular:
1. Active infectious uveitis. However, if the uveitis is the consequence of
a previous infectious disease, such as Tuberculosis, the previous
infectious disease must be confirmed as no longer active
2. Clinically suspected or confirmed central nervous system or ocular
lymphoma
3. Primary diagnosis of anterior uveitis
4. Uncontrolled glaucoma, evidenced by an intraocular pressure of > 21
mmHg while on medical therapy, or chronic hypotony (<6 mmHg)
5. Any implantable corticosteroid-eluting device (e.g. Ozurdex, I-vation, Iluvien, triamcinolone acetonide [TA] intravitreal implant) in the study eye:
a. If the Investigator confirms the device has no demonstrable efficacy as indicated in the package insert, the subject will be eligible;
b. If a Medidur implant, Iluvien or Retisert has, it should have been
implanted no less than 3 years and 90 days prior to Day 1, the subject will be eligible
6. Any significant ocular disease that could compromise vision in the
study eye. These include, but are not limited to:
a. Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or
nonproliferative diabetic retinopathy (NPDR) that compromise vision.
Subjects with NPDR or PDR that does not compromise vision are not
excluded from the study;
b. Wet age-related macular degeneration;
c. Myopic degeneration with active subfoveal choroidal
neovascularization
7. Lens opacities or obscured ocular media other than vitreous haze
upon enrollment
such that reliable evaluations and grading of the posterior segment
cannot be performed
8. Intraocular surgery within 90 days prior to Day 1 in the study eye
9. Capsulotomy within 30 days prior to Day 1 in the study eye
10. Any of the following treatments within 90 days prior to Day 1 or
anticipated use
of any of the following treatments to the study eye:
a. Intravitreal injections (including but not limited to steroids or
antivascular endothelial growth factors);
b. Posterior subtenon steroids
11. Ocular or periocular infection in either eye
12. Pupillary dilation inadequate for quality stereoscopic fundus
photography in the
study eye
13. Media opacity that would limit clinical visualization, intravenous
fluorescein
angiography (IVFA), or OCT evaluation in the study eye
14. History of herpetic infection in the study eye or adnexa
15. Presence of known active, inactive toxoplasmosis or toxoplasmosis
scar in either eye
16. Presence of any form of ocular malignancy in either eye including
choroidal
melanoma
17. History of vitrectomy in the study eye
Non-Ocular:
1. Allergy or hypersensitivity to study drug product or fluorescein dye or
other study related procedures/medications
2. Participation in other investigational drug or device clinical trials
within 30 days prior to Day 1, or planning to participate in otherinvestigational drug or device clinical trials for the entire duration of the
study. This includes both ocular and non-ocular clinical trials.
3. Treatment with a monoclonal antibody or any other biologic therapy
(i.e. Etanercept, Tocilizumab, Adalimumab, Rituximab, etc.) within the
previous 30 days, or with alemtuzumab within the previous 12 months
from Day 1
4. Immunosuppressive therapy (e.g., methotrexate, cyclosporine,
cyclophosphamide, chlorambucil, mycophenolate mofetil, tacrolimus,
azathioprine or colchicine) other than prednisone or other
corticosteroids for the treatment of uveitis within 30 days of the first
study drug administration (Day 1)
5. Any recent systemic infection within 30 days of Screening
6. Known to be immunocompromised
7. History of cytomegalovirus infection or clinical evidence of active
cytomegalovirus infection at Screening and/or Day 1
8. History of other disease, metabolic dysfunction, physical examination
finding, or
clinical laboratory finding giving reasonable suspicion of a disease
condition that
contraindicates the use of an investigational drug, might affect the
interpretation of the results of the study, or renders the subject at high
risk for treatment complications
9. Malignancy in remission for less than 5 years prior to study
participation (except
basal cell or squamous cell skin cancer, or treated melanoma of the skin
less than 24 months since last treatment)
10. Females who are pregnant or lactating and females of child-bearing
potential who
are not using adequate contraceptive precautions (i.e., intrauterine
device, oral
contraceptives, barrier method, or other contraception deemed adequate
by the
Investigator)
11. Use of medically prescribed marijuana or other illegal medication
12. Active systemic sarcoidosis within the last 30 months (i.e. Subjects
with uveitis secondary to sarcoidosis will be eligible as long as systemic
sarcoidosis is not active and systemic immunosuppressive therapy has
not been given in the last 30 months)
In addition, the Investigator or Santen Medical Monitor may declare a
subject ineligible for any sound reason.

E.5 End points

E.5.1

Primary end point(s)

Vitreous haze (VH) 0 response: Having a VH score of 0 at Month 5 based
on the modified Standardized Uveitis Nomenclature (SUN) Photographic
scale.

E.5.1.1

Timepoint(s) of evaluation of this end point

Month 5

E.5.2

Secondary end point(s)

Key Secondary Endpoints:
• VH 0 or 2-unit response: Having a VH score of 0 or a decrease
(improvement) of at least 2 units from baseline in VH score at Month 5 (modified SUN scale)
• VH 0 or 0.5+ response: Having a VH score of 0 or 0.5+ at Month 5
(modified SUN scale)
• Corticosteroid tapering success (for the Intent-to-Taper Population):
The overall prednisoneequivalent dose being tapered off to ≤ 5 mg/day at Month 5.
Other Secondary Endpoints:
• VH 0 response at Month 6: Having a VH score of 0 at Month 6 (modified SUN scale)
• VH 0 or 2-unit response at Month 6: Having a VH score of 0 or a
decrease (improvement) of at least 2 units from baseline in VH score at Month 6 (modified SUN scale)
• VH 0 or 0.5+ response at Month 6: Having a VH score of 0 or 0.5+ at Month 6 (modified SUN scale)
• Change from baseline in VH score at Month 5 (modified SUN scale)
XML File Identifier: TXjGTZmS+vwtzYtRhD0R2UXgUVs=
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• Change from baseline in VH score at Month 6 (modified SUN scale)
• Change from baseline in best-corrected visual acuity (BCVA) at Month 5
• Change from baseline in central retinal thickness at Month 5 as
measured by optical coherence tomography (OCT)
• Change from baseline in the National Eye Institute (NEI) Visual
Functioning Questionnaire-25 (VFQ-25) composite score at Month 5
• Use of rescue therapy before Month 5
• Time to rescue from randomization before Month 5
Other secondary endpoints such as "time to VH score of 0 before Month 5", "having an increase (improvement) of at least 15 letters in BCVA
from baseline at Month 5", and the same set of endpoints at Month 6 that are not listed may also be analyzed for exploratory purposes.

E.5.2.1

Timepoint(s) of evaluation of this end point

Month 5

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

E.6.7

Pharmacodynamic

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)

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

Yes

E.8.1.7.1

Other trial design description

Open label treatment with 880 ug DE-109 after month 5

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Other doses of Sirolimus

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

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

Argentina

Austria

Brazil

Chile

Colombia

Dominican Republic

France

Germany

India

Israel

Italy

Mexico

Peru

Poland

Spain

Turkey

United Kingdom

United States

United States Minor Outlying Islands

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

Last visit of the last patient

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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

520

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

200

F.4.2.2

In the whole clinical trial

600

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)

Not different from standard of care

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

2011-10-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-30

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
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