Clinical Trials Register

Summary
EudraCT Number:	2013-002626-23
Sponsor's Protocol Code Number:	CRFB002A2411
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-12-13
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2013-002626-23

A.3

Full title of the trial

A 12-month, phase IIIb, randomized, visual acuity, assessor-masked, multicenter study assessing the efficacy and safety of ranibizumab 0.5mg in treat and extend regimen compared to monthly regimen, in patients with neovascular age-related macular degeneration

A.3.1

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

Efficacy and safety of two different treatment patterns of ranibizumab in patients with wet AMD

A.3.2

Name or abbreviated title of the trial where available

TREND

A.4.1

Sponsor's protocol code number

CRFB002A2411

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 Pharmaceuticals UK Ltd
B.5.2	Functional name of contact point	Medical Collaboration Centre
B.5.3	Address:
B.5.3.1	Street Address	Frimley Business Park
B.5.3.2	Town/ city	Frimley, Camberley, Surrey
B.5.3.3	Post code	GU16 7SR
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441276698370
B.5.5	Fax number	+441276698449

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	Lucentis
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Lucentis
D.3.2	Product code	RFB002A
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	RANIBIZUMAB
D.3.9.1	CAS number	347396-82-1
D.3.9.2	Current sponsor code	RFB002
D.3.9.4	EV Substance Code	SUB22314
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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.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	Yes
D.2.1.1.1	Trade name	Lucentis
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Lucentis
D.3.2	Product code	RFB002A
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	RANIBIZUMAB
D.3.9.1	CAS number	347396-82-1
D.3.9.2	Current sponsor code	RFB002
D.3.9.4	EV Substance Code	SUB22314
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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

Visual impairment due to neovascular AMD

E.1.1.1

Medical condition in easily understood language

Impaired vision due to growth of new vessels (neovascularization) in the choroid which is caused by an intrinsic substance, so-called vascular endothelial growth factor (VEGF)

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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10060837
E.1.2	Term	Choroidal neovascularization
E.1.2	System Organ Class	100000004853

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to demonstrate that the ranibizumab Treat and Extend regimen is non-inferior to ranibizumab monthly regimen in patients with nAMD as assessed by the change in best corrected visual acuity (BCVA) from baseline to Month 12 .
For the primary analysis a non-inferiority margin of five letters will be applied..

E.2.2

Secondary objectives of the trial

To Evaluate
• the number of visits scheduled according to the TER after treatment initiation.
• the average change in BCVA from baseline to Month1 through Month 12, the time course of mean BCVA from baseline up to Month 12
• the change in BCVA, the occurrence of BCVA losses of <5, <10 and <15 letters and the occurrence of absolute BCVA ≥73 letters (20/40 Snellen equivalent), the occurrence of BCVA improvements of ≥1, ≥5, ≥10, ≥15, and ≥30 letters, the occurrence of a fluid free macula from baseline, over time up to Month 12.
• presence of active CNV leakage on fluorescein angiography (FA) over time up to Month 12
• Assess treatment frequency and average dosing interval and the impact on patient functioning and quality of life supported by ranibizumab 0.5 as assessed by the NEI-VFQ-25
• safety of 0.5 mg ranibizumab over 12 months

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained before any study related procedure is performed.

2. Male or female patients, ≥50 years of age.

Inclusion criteria for the study eye at Screening:
3. Visual impairment predominantly due to nAMD.

4. Active CNV secondary to AMD confirmed by presence of active leakage from CNV seen by fluorescein angiography (FA) and/or color fundus photography

5. Presence of intra- or subretinal fluid/hemorrhage seen by SD-OCT

6. CNV or sequelae of the CNV (i.e., pigment epithelium detachment, subretinal or sub- RPE hemorrhage, blocked fluorescence, macular edema, or subretinal, sub-RPE or intraretinal fluid involving the center of the fovea

7. The total area of fibrosis comprising less than 50% of the lesion area.

8. BCVA score must be ≤ 78 and ≥ 23 letters at 4 meters starting distance using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts (approximate Snellen equivalent of 20/32 and 20/320)

E.4

Principal exclusion criteria

Exclusion criteria for systemic medical history and conditions at Screening:
1. Any type of advanced, severe or unstable disease, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.
2. Stroke or myocardial infarction within 3 months prior to Screening.
3. Presence of uncontrolled systolic blood pressure > 160 mmHg or diastolic blood pressure > 100
mmHg.
4. Known hypersensitivity to the investigational drug (ranibizumab or any component of the Ranibizumab formulation) or to drugs of similar chemical class or to fluorescein or any other component of fluorescein formulation.

Exclusion criteria for ocular medical history and conditions at Screening:
5. Any active periocular or ocular infection or inflammation in both eyes.
6. Uncontrolled glaucoma (intraocular pressure [IOP] ≥30 mm Hg on medication or according to investigator’s judgment) in the study eye.
7. Atrophy or fibrosis involving the center of the fovea in the study eye.
8. History of focal/grid laser photocoagulation with involvement of the macular area at any time in the study eye.
9. Ocular disorders in the study eye (i.e. retinal detachment, pre-retinal membrane of the macula or cataract with significant impact on visual acuity) at the time of enrollment that may confound interpretation of study results and compromise visual acuity.
10. Presence of amblyopia or ocular disorders with final best corrected vision <20/200 or amaurosis in the fellow eye.

Exclusion criteria for prior or current ocular treatment at Screening:
11. History of treatment with any anti-angiogenic drugs (including any anti-VEGF agents) e.g., bevacizumab [Avastin®], aflibercept [Eylea®]) or vPDT in the study eye.
12. History of intravitreal treatment with corticosteroids within 6 months prior to Screening in the study eye.
13. History of intra-ocular surgery within 3 months in the study eye prior to the Screening. Exclusion criteria for prior or current systemic medication at Screening:
14. Use of other investigational drugs (excluding vitamins, minerals) within 30 days or 5 half-lives from Screening, whichever is longer.
15. Use of any systemic anti-VEGF drugs within 3 months prior to Screening (e.g., bevacizumab [Avastin®], ziv-aflibercept [Zaltrap®]).
16. Current or planned use of systemic medications know to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine (Plaquenil®), tamoxifen, henothiazines and ethambutol.

Exclusion criteria for patient at Screening:
17. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation, confirmed by a positive hCG laboratory test.
18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 m prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository
• Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal
contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or
transdermal hormone contraception
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).

E.5 End points

E.5.1

Primary end point(s)

Change in Best Corrected Visual Acuity (BCVA)

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to month 12

E.5.2

Secondary end point(s)

1) BCVA change over time; by measuring BCVA score at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts
2) Number of visits scheduled
3) avarage change in BCVA; BCVA score measured at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts
4) Period (time) between injections
5) Presence of the disease activity measured on the images by Reading center.
6) Change in retinal thickness measured on OCT image by Reading center
7) CNV leakage presence measured on Fluorescein angiography image by Reading center.
8) Quality of Life

E.5.2.1

Timepoint(s) of evaluation of this end point

From Month 1 through Month 12 (applicable to 1)
From Month 1 to Month 11 (Applicable to 2)
From Baseline to Month 12 (applicable to 3, 4, 5, 6, 7, 8)

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

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

Yes

E.6.13.1

Other scope of the trial description

Treatment monitoring

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

Information not present in EudraCT

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

Yes

E.8.1.7.1

Other trial design description

Assessor masked to treatment regimen

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

Monthly Lucentis regimen vs Treat and Extend Lucentis regimen

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

Belgium

Chile

Croatia

Denmark

Egypt

Germany

Hungary

India

Italy

Korea, Republic of

Portugal

Russian Federation

Serbia

Slovakia

Slovenia

Spain

Switzerland

Turkey

United Kingdom

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

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

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:

258

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

386

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

Legal representative (legally authorized authorised to act as personal representative to sign for patient) may sign ICF

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

483

F.4.2.2

In the whole clinical trial

644

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)

none - Lucentis is available on the market

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

2013-12-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-02-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-11-19

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials