A study to learn how well a higher amount of aflibercept given as an injection into the eye works and how safe it is in people with reduced vision due to swelling in the macula, central part of the retina caused by a blocked vein in the retina (macula edema secondary to retinal vein occlusion)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

13 Sep 2023 → 27 May 2025

Decision date (initial)

2023-08-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bayer AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine if treatment with aflibercept 8 mg every 8 weeks (Q8W) provides non-inferior best-corrected visual acuity (BCVA) change compared to aflibercept 2 mg every 4 weeks (Q4W)

Secondary objectives 6

1. To determine if treatment with aflibercept 8 mg Q8W requires less injections compared to aflibercept 2 mg Q4W
2. To determine the effect of aflibercept 8 mg Q8W compared to aflibercept 2 mg Q4W on other visual and anatomic measures of response
3. To assess the efficacy of aflibercept 8 mg Q8W compared to aflibercept 2 mg aflibercept Q4W on vision-related quality of life (QoL)
4. To evaluate the safety of aflibercept 8 mg Q8W compared to aflibercept 2 mg aflibercept Q4W
5. To evaluate duration of effect of aflibercept 8 mg Q8W compared to aflibercept 2 mg aflibercept Q4W
6. To evaluate the PK of aflibercept 8 mg Q8W compared to aflibercept 2 mg aflibercept Q4W

Conditions and MedDRA coding

Macular edema secondary to retinal vein occlusion

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Adult ≥18 years of age (or country’s legal age of adulthood if the legal age is >18 years) at the time of signing the informed consent
2. Treatment-naïve macular edema involving the foveal center secondary to retinal vein occlusion (RVO) (branch RVO (BRVO), hemiretinal vein occlusion (HRVO), or central RVO (CRVO)) diagnosed within 16 weeks (112 days) before the screening visit in the study eye.
3. Early Treatment Diabetic Retinopathy Study BCVA letter score of 73 to 24 (20/40 to 20/320) at screening and baseline visits in the study eye.
4. Decrease in BCVA determined to be primarily the result of RVO in the study eye.
5. Mean central subfield thickness (CST) ≥300 µm on optical coherence tomography (OCT) if excluding Bruch’s membrane (e.g., Cirrus or Topcon) or ≥320 µm if including Bruch’s membrane (e.g., Heidelberg Spectralis), confirmed by the reading center at the screening visit and by the site at baseline visit in the study eye.
6. Capable of giving signed informed consent form (ICF) by study participant or legally acceptable representative, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
7. US participants will be required to have a Health Insurance Portability and Accountability Act (HIPAA) authorization; in other countries, as applicable according to national laws.
8. Women of childbearing potential (WOCBP) or men who are sexually active with partners of childbearing potential must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last administration of study intervention. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for participation in clinical studies and fulfil the conditions set on protocol.

Exclusion criteria 12

1. Concurrent disease that causes substantial decrease of BCVA, is expected to limit BCVA recovery or is likely to require medical or surgical intervention during the study in the study eye.
2. Presence or history of the following ocular conditions: a. Advanced age-related macular degeneration (neovascular AMD or geographic atrophy) in the study eye. b. Diabetic macular edema or diabetic retinopathy, defined in diabetic participants as diabetic retinopathy lesions outside the area of the vein occlusion in the study eye and anywhere in the retina in the fellow eye. c. Anterior segment neovascularization, vitreous hemorrhage, retinal detachment in the study eye. d. Vitreomacular traction, epiretinal membrane or structural damage to the macula that is considered by the Investigator to significantly affect central vision or preclude improvement in vision in the study eye. e. Macular hole of stage 2 and above in the study eye. f. Myopia of a spherical equivalent of at least 8 diopters prior to any refractive or cataract surgery in the study eye. g. Corneal transplant or corneal dystrophy in the study eye. h. Idiopathic or autoimmune uveitis in the study or in the fellow eye."
3. Presence of the following ocular conditions at screening or baseline visit: a. Significant media opacities, including cataract, that interfere with BCVA, or imaging assessments (e.g., fundus photography [FP], optical coherence tomography (OCT)) in the study eye. b. Aphakia, or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium-aluminum-garnet [YAG] posterior capsulotomy performed more than 30 days before the screening visit), in the study eye. c. Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication); or history or likely future need of glaucoma surgery in the study eye. d. Intraocular inflammation/infection (including trace, or above, cells in the anterior chamber and/or vitreous) within 12 weeks (84 days) of the screening visit in the study or in the fellow eye. e. Extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in the study or in the fellow eye.
4. Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg) at screening visit or baseline visit.
5. Uncontrolled diabetes mellitus, defined by hemoglobin A1c (HbA1c) >12% at the screening visit.
6. History of cerebrovascular accident or myocardial infarction within 24 weeks (168 days) before the screening visit or between screening and baseline visits.
7. Renal failure requiring dialysis, or renal transplant at screening or potentially during the study.
8. Any prior or concomitant ocular or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for RVO in the study eye.
9. Previous administration of systemic anti-angiogenic medications for any condition.
10. Prior treatment of the study eye with any of the following drugs (any route of ophthalmic administration) or procedures: a. Anti-angiogenic drugs at any time including investigational therapy (e.g., with anti-angiopoietin/anti-VEGF bispecific monoclonal antibodies). b. Previous use topical steroids within 4 weeks (28 days) from the screening visit, or intraocular or periocular steroids within 16 weeks (112 days) from the screening visit, or steroid implants at any time. c. Previous treatment with intraocular or periocular implant, gene therapy, or cell therapy at any time. d. Treatment with ocriplasmin at any time. e. Vitreoretinal surgery (including scleral buckling) at any time. f. Any intraocular surgery, including cataract surgery, within 12 weeks (84 days) before the screening visit. g. Previous treatment with retinal laser photocoagulation.
11. Prior treatment of the fellow eye with any of the following: a. Gene therapy, or cell therapy in the fellow eye at any time.
12. Participation in other clinical studies requiring administration of investigational treatments (other than vitamins and minerals) at the time of screening visit, or within 30 days or 5 half-lives of administration of the previous study intervention, whichever is longer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in BCVA measured by the ETDRS letter score at Week 36

Secondary endpoints 14

1. Number of active injections from baseline to Week 64
2. Number of active injections from baseline to Week 36
3. Change from baseline in BCVA measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at Week 44
4. Change from baseline in BCVA measured by the ETDRS letter score at Week 64
5. Participant gaining at least 15 letters in BCVA from baseline at Weeks 36 and 64
6. Participant achieving an ETDRS letter score of at least 69 (approximate 20/40 Snellen equivalent) at Weeks 36 and 64
7. Participant having no intraretinal fluid (IRF) and no sub-retinal fluid (SRF) in the center subfield at Weeks 36 and 64
8. Change from baseline in CST at Weeks 36 and 64
9. Change from baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) total score at Weeks 36 and 64
10. Occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) through Weeks 36 and 64
11. Participant dosed only Q8W through Week 36 in the 8 mg Q8W group
12. Participant having last treatment interval ≥12 or of 16 weeks at Week 64
13. Participant having next intended interval ≥12, ≥16 or of 20 weeks at Week 64
14. Systemic exposure to aflibercept as assessed by plasma concentrations of free, adjusted bound and total aflibercept from baseline through Weeks 36 and 64

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bayer AG

Sponsor organisation

Bayer AG

City

Leverkusen

Postcode

51368

Country

Germany

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Third parties 4

Locations

14 EU/EEA countries · 97 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 78 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

23 submissions — initial application plus substantial / non-substantial modifications