ICH GCP - EU Clinical trials Registry - 2022-000690-73 (DE)-ICH GCP

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Summary
EudraCT Number:	2022-000690-73
Sponsor's Protocol Code Number:	BAY86-5321/21912
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-07-15
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

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2022-000690-73

A.3

Full title of the trial

A Parallel-group Phase 4, Open-label, Two-arm Study to Assess the Safety and Efficacy of Intravitreal (IVT) Aflibercept with Proactive customized Treatment Intervals in Patients ≥50 Years of Age with No Fluid Due to Choroidal Neovascularization (CNV) Lesions Secondary to Neovascular (wet) Age-related Macular Degeneration (nAMD) Following Treatment Initiation with Aflibercept

A.3.1

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

A study to learn how well Aflibercept injected into the eye works and how safe it is when given in customized treatment intervals in patients with an eye disease called neovascular age-related macular degeneration after start of treatment

A.3.2

Name or abbreviated title of the trial where available

XPAND

A.4.1

Sponsor's protocol code number

BAY86-5321/21912

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	Bayer AG
B.1.3.4	Country	Germany
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	Bayer AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer AG
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	CTP Team/Ref:”EU CTR”/Bayer AG
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.6	E-mail	clinical-trials-contact@bayer.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	Eylea 40mg/ml solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer AG
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	Aflibercept
D.3.2	Product code	BAY 86-5321
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	Aflibercept
D.3.9.1	CAS number	862111-32-8
D.3.9.2	Current sponsor code	BAY 86-5321
D.3.9.3	Other descriptive name	VEGF Trap-Eye
D.3.9.4	EV Substance Code	SUB26987
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	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	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	Yes
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

Neovascular (wet) age-related macular degeneration

E.1.1.1

Medical condition in easily understood language

An eye disorder caused by abnormal blood vessels that leak fluid into the central part of the retina at the back of the eye leading to blurring or a blind spot in the central (straight ahead) vision

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10071129
E.1.2	Term	Neovascular age-related macular degeneration
E.1.2	System Organ Class	10015919 - Eye disorders

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 assess whether 2 mg intravitreal (IVT) aflibercept administered at a customized treatment interval (determined after the first extended treatment interval) is non-inferior to 2 mg IVT aflibercept administered according to a standard treat and extend (T&E) regimen (initiated after the first extended treatment interval) in patients with no fluid following treatment initiation for neovascular (wet) age-related macular degeneration (nAMD)

E.2.2

Secondary objectives of the trial

1. To assess treatment burden of 2 mg IVT aflibercept administered at a customized treatment interval compared with 2 mg IVT aflibercept administered according to a standard T&E regimen (initiated after the first extended treatment interval) in patients with no fluid following treatment initiation for nAMD
2. To evaluate the safety of aflibercept with proactive treatment intervals

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent and able to read (or if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member), understand, and willing to sign the ICF.
2. Men and women ≥50 years of age.
3. At treatment initiation, active macular neovascular lesions secondary to nAMD (Patients with polypoidal choroidal vasculopathy or retinal angiomatous proliferation are eligible to participate in the study, and their condition should be captured in the electronic case report form [eCRF]).
4. Treatment initiation with 3 × monthly IVT aflibercept injections (Weeks -16, -12, and -8 to planned study baseline visit) resulting in absence of any fluid at week -8.
5. ETDRS BCVA of at least 25 letters (20/320 Snellen equivalent) in the study eye at screening visit.
6. Willing, committed, and able to return for all clinic visits and complete all study-related procedures.
7. Able to use the provided monitoring device and willing to perform 5 × weekly self-assessments in the Investigator’s opinion.
8. Women and men of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time period between signing of the ICF and 3 months after the last administration of study drug.

E.4

Principal exclusion criteria

1. Any contraindication to IVT anti-VEGF treatment or treatment with Eylea® as detailed in the Summary of Product Characteristics (SmPC).
2. Any prior ocular (in the study eye) or systemic treatment (including investigational agents) or surgery for nAMD, except the 3 × monthly IVT aflibercept injections required for treatment initiation and dietary supplements or vitamins.
3. Any presence of intraretinal and subretinal fluid.
4. Any ocular or systemic condition expected to interfere with study outcomes and procedures, including but not limited to:
• Scar, fibrosis or other lesions (e.g., retinal pigment epithelium [RPE] tears, macular hole stage 2 or above and others) involving the center of the macula in the study eye.
• Clinically relevant opacities or conditions involving the optic media including cataract, corneal dystrophies or s.p. corneal transplant in the study eye.
• Uncontrolled glaucoma (defined as IOP ≥25 mm Hg despite treatment with antiglaucoma medication) in the study eye or prior trabeculectomy or other filtration surgery in the study eye.
• Intraocular surgery, periocular surgery, or cataract surgery within 90 days before Day 1 in the study eye, except the IVT aflibercept injections required for treatment initiation and any history of vitrectomy, retinal radiation therapy, retinal detachment or treatment or surgery for retinal detachment in the study eye.
• Aphakia or pseudophakia with absence of posterior capsule (unless as a result of an yttrium aluminum garnet posterior capsulotomy) in the study eye.
5. Participation as a patient in any clinical study within 12 weeks before screening.
6. Close affiliation with the investigational site; e.g., a close relative of the Investigator, dependent person (e.g., employee or student of the investigational site).
7. Previously screen failed patients for this study

E.5 End points

E.5.1

Primary end point(s)

Change in best-corrected visual acuity (BCVA) (early treatment diabetic retinopathy study [ETDRS] letters)

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to Week 36

E.5.2

Secondary end point(s)

1. Number of IVT aflibercept injections per patient
2. Number of IVT aflibercept injections per patient
3. Number of patients achieving pre-defined treatment intervals (≥4, ≥8, ≥10, ≥12¸ ≥14, and 16 weeks)
4. Change in BCVA (ETDRS letters)
5. Number of subjects with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. From baseline up to Week 52
2. From baseline up to Week 36
3. At Weeks 36 and 52
4. From baseline up to Week 52
5. From baseline up to Week 36 and Week 52

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Standard treat and extend regimen-2 week-adjustment

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

Canada

France

Spain

Germany

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

Last subject last visit

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

103

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

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

F.4.2.2

In the whole clinical trial

108

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

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

2022-08-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-06-06

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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