Efficacy and safety of high-dose Aflibercept in macular edema due to retinal vein occlusion (short: "RVO")
Zusammenfassung der Studie
We are conducting this study because researchers are looking for an improvement in the treatment of patients with retinal vein occlusion (RVO). This involves a blockage in the blood vessels that drain the retina of the eye. As a result, fluid accumulates in the retina, and especially the so-called macula, which is the area of sharpest vision in the center of the retina, swells (this is called "macular edema") and vision is impaired. The drug being studied, Aflibercept, is approved in Switzerland for the treatment of this condition. It is injected into the eye every 4 weeks at a dose of 2 mg. Such short intervals between injections are a burden for the affected individuals. A higher dose of Aflibercept with injections of 8 mg has already been tested in other studies. It was found that the drug needed to be injected less frequently. The aim of this study is to investigate whether therapy with the higher dose of Aflibercept also works for those affected by RVO. Since it is not yet known whether the high dose for treating macular edema due to RVO is better than the currently available dose, the two doses (2 mg versus 8 mg) need to be compared. This will be determined using standardized vision tests and eye examinations. Additionally, we also investigate the tolerability and safety of the therapies. There are 3 treatment groups with the following treatment: 1. Aflibercept 8 mg or placebo injection, first 3 injections every 4 weeks, then every 8 weeks, then adjustment of intervals based on the effect of the therapy 2. Aflibercept 8 mg or placebo injection, first 5 injections every 4 weeks, then every 8 weeks, then adjustment of intervals based on the effect of the therapy 3. Aflibercept 2 mg every 4 weeks for 32 weeks, then adjustment of intervals based on the effect of the therapy. The therapy will be administered in all groups for 60 weeks.
(BASEC)
Untersuchte Intervention
Injections of Aflibercept at a high dose of 8 mg into the studied eye. Injection of Aflibercept (Eylea) at the dose approved in Switzerland of 2 mg into the studied eye. Placebo injections into the studied eye. In this case, the syringe is placed without a needle simply on the eye.
(BASEC)
Untersuchte Krankheit(en)
Macular edema due to retinal vein occlusion (RVO). This means that due to the blockage of veins (blood-draining blood vessels) in the retina of the eye, fluid accumulates, negatively affecting vision and damaging the retina.
(BASEC)
- Minimum age of 18 years. - An untreated macular edema due to retinal vein occlusion (RVO, diagnosed within 16 weeks prior to the preliminary examination (screening date). - Visual disturbances attributed to RVO as determined by the investigator. (BASEC)
Ausschlusskriterien
- Other diseases affecting vision. - Other severe eye diseases (in the past and currently). - At the preliminary examination (screening date), the following eye diseases are found: lens opacity (cataract), uncontrolled elevated intraocular pressure (glaucoma), infection and/or inflammation of the eye or absence of the lens in the eye. (BASEC)
Studienstandort
Basel, Bern, Lausanne, Zürich
(BASEC)
Sponsor
Bayer AG, Leverkusen Bayer (Schweiz) AG
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Sophia Birnbaum
+41 44 465 81 11
clinical.operations.switzerland@clutterbayer.comBayer (Schweiz) AG Uetlibergstrasse 132 8045 Zürich
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
29.09.2023
(BASEC)
ICTRP Studien-ID
NCT05850520 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of Aflibercept 8 mg in Macular Edema Secondary to Retinal Vein Occlusion (BASEC)
Wissenschaftlicher Titel
Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of Aflibercept 8 mg in Macular Edema Secondary to Retinal Vein Occlusion (ICTRP)
Öffentlicher Titel
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) (ICTRP)
Untersuchte Krankheit(en)
Macular Edema Secondary to Retinal Vein Occlusion (ICTRP)
Untersuchte Intervention
Drug: Aflibercept, VEGF Trap-Eye(Eylea, BAY86-5321)_higher doseDrug: Aflibercept, VEGF Trap-Eye(Eylea, BAY86-5321)_2 mgDrug: ShamDiagnostic Test: Fluorescein (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion Criteria:
- 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.
- Treatment-nave macular edema involving the foveal center secondary to RVO (BRVO,
HRVO, or CRVO) diagnosed within 16 weeks (112 days) before the screening visit in
the study eye.
- 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.
Decrease in BCVA determined to be primarily the result of RVO in the study eye.
- Mean CST =300 m on optical coherence tomography (OCT) if excluding Bruch's membrane
(e.g., Cirrus or Topcon) or =320 m 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.
- 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.
- 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.
- 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
Section 10.4.2.
Exclusion Criteria:
- 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.
- Presence or history of the following ocular conditions:
1. Advanced age-related macular degeneration (neovascular AMD or geographic
atrophy) in the study eye.
2. 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.
3. Anterior segment neovascularization, vitreous hemorrhage, retinal detachment in
the study eye.
4. 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.
5. Macular hole of stage 2 and above in the study eye.
6. Myopia of a spherical equivalent of at least 8 diopters prior to any refractive
or cataract surgery in the study eye.
7. Corneal transplant or corneal dystrophy in the study eye.
8. Idiopathic or autoimmune uveitis in the study or in the fellow eye.
- Presence of the following ocular conditions at screening or baseline visit:
1. Significant media opacities, including cataract, that interfere with BCVA, or
imaging assessments (e.g., fundus photography [FP], OCT) in the study eye.
2. 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.
3. 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.
4. 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.
5. Extraocular or periocular infection or inflammation (including infectious
blepharitis, keratitis, scleritis, or conjunctivitis) in the study or in the
fellow eye.
- Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg) at
the screening visit or baseline visit.
- Uncontrolled diabetes mellitus, defined by hemoglobin A1c (HbA1c) >12% at the
screening visit.
- History of cerebrovascular accident or myocardial infarction within 24 weeks (168
days) before the screening visit or between screening and baseline visits.
- Renal failure requiring dialysis, or renal transplant at screening or potentially
during the study.
- 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.
- Previous administration of systemic anti-angiogenic medications for any condition.
- Prior treatment of the study eye with any of the following drugs (any route of
ophthalmic administration) or procedures:
1. Anti-angiogenic drugs at any time including investigational therapy (e.g., with
anti-angiopoietin/anti-VEGF bispecific monoclonal antibodies).
2. 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.
3. Previous treatment with intraocular or periocular implant, gene therapy, or
cell therapy at any time.
4. Treatment with ocriplasmin at any time.
5. Vitreoretinal surgery (including scleral buckling) at any time.
6. Any intraocular surgery, including cataract surgery, within 12 weeks (84 days)
before the screening visit.
7. Previous treatment with retinal laser photocoagulation.
- Prior treatment of the fellow eye with any of the following:
a. Gene therapy, or cell therapy in the fellow eye at any time.
- 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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 36 (ICTRP)
Number of Active Injections From Baseline to Week 36;Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 36;Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 36;Participants Having no Intraretinal Fluid (IRF) and no Sub-retinal Fluid (SRF) in the Center Subfield at Week 36;Change From Baseline in Central Sub-field Thickness (CST) at Week 36;Change From Baseline in NEI VFQ 25 Total Score at Week 36;Participants Dosed Only Q8 Through Week 36 in the 8 mg Q8 Group;Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Weeks 36;Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Weeks 36 (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
Regeneron Pharmaceuticals (ICTRP)
Weitere Kontakte
Bayer Clinical Trials Contact, clinical-trials-contact@bayer.com, (+)1-888-84 22937 (ICTRP)
Sekundäre IDs
2022-502174-16-00, 22153 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT05850520 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
52b-b-273383-che-for-publication-layperson-summary-of-results-fr-20260410.pdfLink zu den Ergebnissen im Primärregister
nicht verfügbar