Neoplasms

Symptoms and General Pathology

All Conditions

Eye Diseases

Heart and Blood Diseases

Neoplasm Metastasis

Macular Edema

Macular Degeneration

Edema

Retinal Vein Occlusion

Neovascularization, Pathologic

Choroidal Neovascularization

Neoplastic Processes

Retinal Degeneration

Retinal Diseases

Thrombosis

Venous Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

Antineoplastic Agents

All Drugs and Chemicals

Ranibizumab

Angiogenesis Inhibitors

Growth Inhibitors

Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) for 24 months.

Ranibizumab intravitreal injection 0.5 mg in a single-dose regimen given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year).

Ranibizumab 0.5 mg

Phillip Lai, M.D.

This is an open-label, multicenter, extension study of intravitreally administered ranibizumab in two cohorts. The first cohort (reported separately under FVF3426g, NCT00379795) enrolled subjects with primary or recurrent Choroidal Neovascularization (CNV) secondary to Age-Related Macular Degeneration (AMD) who completed the treatment phase of a Genentech sponsored study (FVF2598g (NCT00056836), FVF2587g (NCT00061594), or FVF2428g (NCT00056823)). The second cohort (reported here) enrolled subjects with macular edema secondary to Retinal Vein Occlusion (RVO) who completed the 6-month treatment and 6-month observation phases (12 months total) of a Genentech sponsored study (FVF4165g (NCT00486018) or FVF4166g (NCT00485836)). Patients were enrolled within 14 days of completion of the previous study.

An Extension Study to Evaluate Safety and Tolerability of Ranibizumab in Macular Edema Secondary to Retinal Vein Occlusion (Cohort 2)

An Open-Label, Multicenter Extension Study to Evaluate the Safety and Tolerability of Ranibizumab in Subjects With Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD) or Macular Edema Secondary to Retinal Vein Occlusion (RVO) Who Have Completed a Genentech-Sponsored Ranibizumab Study

Number of participants with: any ocular adverse events, ocular adverse events causing treatment discontinuation, ocular serious adverse events, intraocular inflammation and cataracts that occurred in the study eye.

Only adverse events that occurred during this extension study are reported. For subjects in the crossover groups who started their first ranibizumab injection in this extension study, adverse events that occurred prior to any ranibizumab injection were also excluded.

Number of participants with non-ocular adverse events (not occurring in the eye) in the following categories: any adverse events, serious adverse events, adverse events leading to study discontinuation and death.

Only adverse events that occurred during this extension study are reported. For subjects in the crossover groups who started their first ranibizumab injection in this extension study, adverse events that occurred prior to any ranibizumab injection were also excluded.

Additional information about adverse events can be found in the adverse events section.

Change from baseline in then BCVA was assessed by the number of letters a patient could read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) Eye Chart at a Starting Test Distance of 4 Meters. An increase in the number of letters read indicates improvement in visual acuity.

Change from baseline in Central foveal (retinal) thickness was assessed by Optical Coherence Tomography (OCT). OCT was conducted at the study sites by personnel who were certified by the University of Wisconsin Fundus Photograph Reading Center.

NEI VFQ-25 is a 25 item questionnaire that assesses visual function and quality of life for a total possible score of 0 to 100. A higher score represents better functioning. The change from baseline is calculated at Month 12 and Month 24.

Participants are grouped according to the treatment they received in initial studies FVF4165g BRAVO (NCT00486018) and FVF4166g CRUISE (NCT00485836).

Genentech, Inc.

Safety Population included all participants who received at least one dose of study drug in one of the initial studies or this extension study. These analyses include only those adverse events that occurred during this extension study.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO or the 6 month treatment period of CRUISE and received Ranibizumab during the 6 month observation period of the initial study or this extension study.

Ranibizumab (Sham)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO or the 6 month treatment period of CRUISE.

Ranibizumab (0.3 mg)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO or the 6 month treatment period of CRUISE.

Ranibizumab (0.5 mg)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.

Ranibizumab (Sham BRAVO)

In this extension study participant received Ranibizumab 0.5 mg intravitreal injection administered as needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.

Ranibizumab (0.3 mg BRAVO)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.

Ranibizumab (0.5 mg BRAVO)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.

Ranibizumab (Sham CRUISE)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.

Ranibizumab (0.3 mg CRUISE)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.

Ranibizumab (0.5 mg CRUISE)

Total

<45 years

45 to <65 years

65 to <85 years

≥85 years

Age, Customized

Sex: Female, Male

Genentech

Any ocular adverse event (AE)

Ocular AE leading to treatment discontinuation

Ocular serious adverse event

Intraocular inflammation

Cataract

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received sham intravitreal injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibuzumab intravitreal injections in the 6 month treatment period of CRUISE.

Ranibizumab- Treated Participants includes all participants who received Ranibizumab in one of the initial studies or this extension study. This analysis includes only those adverse events that occurred during this extension study.

Number of Participants With Ocular Adverse Events in the Study Eye

Any non-ocular adverse event

Serious non-ocular adverse event

Non-ocular adverse event led to discontinuation

Death

Number of Participants With Non-ocular Adverse Events

Month 6 (n=88,96,98,90,101,91)

Month 12 (n=66,66,73,58,69,50)

Month 18 (n=23,26,32,31,26,22)

Month 24 (n=0,2,0,0,1,0)

Enrolled participants for whom data was available for analyses at the given time-points. Observed data were used with no imputation. The number of participants for whom data was available for analyses is represented by "n".

Change From Baseline in the Best Corrected Visual Acuity (BCVA)

Month 6 (n=86,96,97,90,101,89)

Month 12 (n=62,65,72,56,69,51)

Enrolled participants for whom data was available for analyses at the given time-point as indicated by "n" in the categories. Observed data were used with no imputation.

Change From Baseline in Central Foveal Thickness at Month 6 and Month 12

Month 12 (n=64,65,72,58,67,50)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of BRAVO and received ranibizumab in the 6 month observation period of BRAVO or in this extension study.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year)for 24 months. Participants in this group received sham intravitreal injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of CRUISE.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection as-needed administered no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Participants in this group received 0.5 mg Ranibuzumab intravitreal injections in the 6 month treatment period of CRUISE.

Change From Baseline in Visual Function Composite Score, as Measured by the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25)

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.3 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received 0.5 mg Ranibizumab intravitreal injections in the 6 month treatment period of BRAVO.

In this extension study participants received Ranibizumab 0.5 mg intravitreal injection administered as-needed no more frequently than every 30 days (no more than 12 injections per year) up to 24 months. Participants in this group received intravitreal sham injections in the 6 month treatment period of CRUISE and received ranibizumab in the 6 month observation period of CRUISE or in this extension study.

Overall Study

Nervous System Diseases

Vision, Low

Pharmaceutical Solutions

Aflibercept

Higher dose of aflibercept is administered with initial initiation doses intervals, followed by extension of treatment intervals and further adjustment of intervals according to treatment response.

Aflibercept 2 mg is administered by standard treatment intervals, followed by adjustment of treatment intervals according to treatment response.

Aflibercept, VEGF Trap-Eye(Eylea, BAY86-5321)_higher dose

Aflibercept, VEGF Trap-Eye(Eylea, BAY86-5321)_2 mg

Sham procedure will be given on visits when an active injection is not planned.

Sham

Fluorescein 100 mg/mL solution for injection is a dye that makes the retinal vessels visible during FA examinations, and as such, it will be used as an auxiliary medicinal product (AxMP) in this periodic ophthalmic examination. This medicine is for diagnostic use only. It is not used to treat any condition.

Fluorescein

Bayer Clinical Trials Contact

Researchers are looking for a better way to treat people who have macular edema secondary to retinal vein occlusion (RVO).

In people with RVO, a blood vessel that carries blood away from the retina (vein) becomes blocked. The retina is the very back part of the eye. The blocked vein causes fluid and blood to leak into the retina and thereby causes a swelling of the macula (the center of the retina responsible for fine vision). This swelling is called macular edema.

When a vein in the retina is blocked, the levels of a protein called vascular endothelial growth factor (VEGF) rises. VEGF helps the growth of new blood vessels. This can lead to macular edema and may cause the vision to become blurry.

The study treatment intravitreal (IVT) aflibercept is given as an injection into the eye. It works by blocking VEGF and this can help repair vision problems related to RVO. IVT aflibercept is already available and is prescribed by doctors as the standard of care treatment for macula edema secondary to RVO. Standard of care is a treatment that medical experts consider most appropriate for a disease.

Standard of care is given every 4 weeks in people with macula edema secondary to RVO. While repeated injections of aflibercept may prevent worsening of vision, it may place a burden on the patient. However, a higher amount (8 mg) compared to the standard of care (2 mg) of IVT aflibercept is being tested in studies. This higher amount could be given less often. The amount of IVT aflibercept given is measured in milligrams, also known as mg.

The main purpose of this study is to learn how well a higher amount of the study treatment aflibercept works in people with macular edema secondary to RVO. To answer this, researchers will measure changes in vision called best corrected visual acuity (BCVA) in the study participants between study start and after 36 weeks of treatment. Changes will then be compared between those participants who received the higher amount of IVT aflibercept and those that received standard of care.

To learn how safe the study treatment is in the participants, the researchers will count the number of participants from study start and up to 64 weeks later that have:

* adverse events
* serious adverse events

"Adverse events" are any medical problems that the participants have during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think they might be related to the study treatments. An adverse event is considered "serious" when it leads to death, puts the participants' lives at risk, requires hospitalization, causes disability, causes a baby being born with medical problems or is otherwise medically important.

Dependent on the treatment group, the participants will either receive the higher amount of aflibercept or standard of care as an intravitreal injection for up to 60 weeks. The study will consist of a test (screening) phase, a treatment phase and an end of study phase. Each participant will be in the study for up to 64 weeks.

One visit to the study site is planned during the screening phase, followed by visits approximately every 4 weeks (16 in total) during treatment and one visit at the end of the study.

During the study, the study doctors and their team will:

* check patients' eye health using various eye examination techniques
* measure patients' eye vision (BCVA)
* take blood and urine samples
* do physical examinations
* check vital signs
* examine heart health using electrocardiogram (ECG)
* do pregnancy tests in women of childbearing age

In addition, participants will be asked to fill a questionnaire on vision-related quality of life.

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)

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

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.

BCVA: Best-Corrected Visual Acuity; ETDRS: Early Treatment Diabetic Retinopathy Study; ETDRS letter score (ranging from 0 to 100 letters). A higher letter score means a better outcome (better visual acuity)

ETDRS letter score (ranging from 0 to 100 letters). A higher letter score means a better outcome (better visual acuity)

NEI-VFQ-25: National Eye Institute Visual Functioning Questionnaire-25; The NEI VFQ-25 total score ranges from 0 to 100. A higher score means a better outcome (better patient-reported visual function).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Extension Study to Evaluate Safety and Tolerability of Ranibizumab in Macular Edema Secondary to Retinal Vein Occlusion (Cohort 2)	NCT01442064	Macular Edema Retinal Vein Oc...	Ranibizumab 0.5...	18 Years -	Genentech, Inc.
An Extension Study to Evaluate Safety and Tolerability of Ranibizumab in Macular Edema Secondary to Retinal Vein Occlusion (Cohort 2)	NCT01442064	Macular Edema Retinal Vein Oc...	Ranibizumab 0.5...	18 Years -	Genentech, Inc.
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)	NCT05850520	Macular Edema S...	Aflibercept, VE... Aflibercept, VE... Sham Fluorescein	18 Years -	Bayer
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)	NCT05850520	Macular Edema S...	Aflibercept, VE... Aflibercept, VE... Sham Fluorescein	18 Years -	Bayer

Spots Global Cancer Trial Database for macular edema secondary to retinal vein occlusion