Efficacy and safety of two different aflibercept regimens in subjects with nAMD.

• Register: EUCTR
• Last refreshed on: 6 July 2020
• Main ID: EUCTR2013-000120-33-AT
• Date of registration: 02/07/2015
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: Efficacy and safety of two different aflibercept regimens in subjects with nAMD.
• Scientific title: An open-label, randomized, active-controlled, parallel-group, Phase-3b study of the efficacy, safety, and tolerability of 2 mg aflibercept administered by intravitreal injections using two different treatment regimens to subjects with neovascular age-related macular degeneration (nAMD). - AZURE
• Date of first enrolment: 22/09/2015
• Target sample size: 330
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000120-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Aflibercept; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Canada, Czech Republic, France, Germany, Hungary, Italy, Lithuania, Poland, Portugal, Slovakia, Spain, Switzerland, United Kingdom

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

Key inclusion & exclusion criteria

Inclusion criteria:
First set of inclusion criteria:
All of the following criteria must have been met at the initial start of aflibercept treatment (i.e. start of aflibercept treatment prior to this study) for a subject to be eligible for this study.
1. Subject had primary subfoveal choroidal neovascularization (CNV) lesions secondary to nAMD, including juxtafoveal lesions that affect the fovea, as evidenced by FA of the study eye within 4 weeks before the initiation of aflibercept treatment.
2. The area of CNV occupied at least 50% of the total lesion within 4 weeks before the initiation of aflibercept treatment.
3. Documented BCVA was 20/40 to 20/320 (comparable to a letter score of 73 to 25) in the study eye at the initiation of treatment (the initial BCVA of the study eye before treatment initiation must be documented as Snellen equivalent in the electronic case report form [eCRF]).
Second set of inclusion criteria:
All of the following criteria must be met at the time of screening for participation in this study for a subject to be eligible for this study.
4. Signed written informed consent
5. Men or women = 51 years of age
6. The subject’s history of aflibercept treatment meets ALL of the following:
a) Treatment in the study eye was initiated with three monthly (-1 week/+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed
b) Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks (one exception will be allowed)
c) The interval between the last two pre-study injections was =8 weeks, and visual and anatomic outcomes have been stable over this interval.
d) The subject received the last IVT injection of aflibercept in the study eye 2 months (+/- 10 days) before the first treatment in this study
e) Total prior treatment duration with aflibercept (i.e. from first treatment to randomization into this study) was =12 months
7. Subject is willing, committed, and able to return for ALL clinic visits and complete all study-related procedures.
8. Women and men of reproductive potential must agree to a method of highly effective contraception (as defined by the Clinical Trial Facilitation Group [CTFG] from 15 SEP 2014):
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
o oral
o intravaginal
o transdermal
•Progestogen-only hormonal contraception associated with inhibition of ovulation:
o oral
o injectable
o implantable
• Intrauterine device
• Intrauterine hormone-releasing system
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence
Alternatively women and men of reproductive potential can also use two acceptable methods of contraception (as defined by the CTFG from 15 SEP 2014) simultaneously:
• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
• Male or female condom with or without spermicide
• Cap, diaphragm or sponge with spermicide
Contraception has to be used from signing the informed consent form until 3 months after the last administration of study drug. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of s
Exclusion criteria:
First set of exclusion criteria:
A subject who has met any of the following criteria at the initial start of aflibercept treatment (i.e. start of aflibercept treatment before this study) will be excluded from this study.
1. Any prior or concomitant therapy with an investigational or approved agent to treat neovascular AMD in the study eye.
2. Total lesion size > 12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by FA in the study eye
3. Subretinal hemorrhage that was:
a) 50% or more of the total lesion area, or
b) if the blood was under the fovea, and
c) the blood under the fovea was 1 or more disc areas in size in the study eye.
4. Scar or fibrosis making up more than 50% of the total lesion in the study eye.
5. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
6. Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
7. Causes of CNV other than AMD in the study eye.
Second set of exclusion criteria:
A subject who meets any of the following criteria at the time of screening for participation in this study will be excluded from this study.
8. Subjects who currently meet any of the first set of exclusion criteria with the exception of prior treatment with aflibercept
9. Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD, except dietary supplements, vitamins and IVT injections of aflibercept, during the time (i.e. at least 12 months) between initiation of aflibercept treatment and randomization into this study
10. Any prior treatment with anti-VEGF therapy in the study eye, with the exception of IVT injections of aflibercept, during the time (i.e. at least 12 months) between initiation of aflibercept treatment and randomization into this study
11. Prior systemic anti-VEGF therapy, investigational or approved, within the last 15 months prior to randomization
12. Any vitreous hemorrhage within 4 weeks before randomization in the study eye
13. Active intraocular, extraocular and periocular inflammation or infection in either eye.
14. Any ocular or periocular infection within 4 weeks of randomization in either eye
15. Any serious adverse event related to aflibercept during prior treatment
16. Any history of allergy or hypersensitivity to povidone iodine.
17. Known serious allergy or hypersensitivity to the fluorescein sodium for injection in angiography
18. Presence of any contraindications indicated in the EU commission/locally approved label for aflibercept: Hypersensitivity to the active substance aflibercept or to any of the excipients; active or suspected ocular or periocular infection; active severe intraocular inflammation
19. Prior vitrectomy in the study eye
20. History of vitreomacular traction in the study eye
21. History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
22. Any history of macular hole of stage 2 and above in the study eye
23. Prior trabeculectomy or other filtration surgery in the study eye
24. Uncontrolled glaucoma (defined as intraocular pressure more than 25 mmHg despite treatment with antiglaucoma medication) in the study eye
25. Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of an yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye
26. Previous therapeutic radiation in the region of the study eye
27. History of corneal transplant or corne

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neovascular Age-Related Macular Degeneration (nAMD)
MedDRA version: 19.0 Level: PT Classification code 10071129 Term: Neovascular age-related macular degeneration System Organ Class: 10015919 - Eye disorders
MedDRA version: 19.0 Level: SOC Classification code 10015919 Term: Eye disorders System Organ Class: 10015919 - Eye disorders

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Intervention(s)

Trade Name: Eylea 40mg/ml solution for injection in a vial
Product Name: Aflibercept
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AFLIBERCEPT
CAS Number: 862111-32-8
Current Sponsor code: BAY 86-5321
Other descriptive name: VEGF Trap-Eye / AFLIBERCEPT
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Primary end point(s): Change in ETDRS BCVA letter score for the study eye from baseline
to Week 52.

Secondary Objective: To assess the safety and tolerability of aflibercept in this subject population.

Main Objective: To compare the efficacy of 2 mg aflibercept administered by two different
intravitreal (IVT) treatment regimens to subjects with nAMD.

Timepoint(s) of evaluation of this end point: Week 52

Secondary Outcome(s)

Secondary end point(s): Efficacy assessments:
- Proportion of subjects maintaining vision (i.e. loss of < 15 letters) in
the study eye at Week 52
- Proportion of subjects who gained = 5 letters from baseline to
Week 52
- Mean change in central retinal thickness (CRT) in the study eye from
baseline to Week 52
- Mean change in CNV area in the study eye from baseline to Week 52
- Proportion of subjects who lost = 30 letters from baseline to Week 52
- Mean change from baseline to Week 52 in total score for NEI VFQ-25

Timepoint(s) of evaluation of this end point: Baseline, Week 52.

Secondary ID(s)

2013-000120-33-HU

BAY86-5321/16598

Source(s) of Monetary Support

Bayer AG

Ethics review

Status: Approved
Approval date: 09/09/2015
Contact: