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Intravitreal Aflibercept in Neovascular AMD With Limited Response to Ranibizumab

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ClinicalTrials.gov Identifier: NCT02309281
Recruitment Status : Completed
First Posted : December 5, 2014
Last Update Posted : October 16, 2018
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Dr. med. Katja Hatz, Vista Klinik

Brief Summary:

Title: Intravitreal aflibercept (VEGF Trap-Eye) in neovascular age-related macular degeneration with limited response to ranibizumab

Purpose: The purpose of this investigator initiated study is to identify the duration of treatment effects of intravitreal aflibercept on sub- and intraretinal fluid and best corrected visual acuity (BCVA) in choroidal neovascularizations (CNV) due to age-related macular degeneration (AMD) in which the Optical coherence tomography (OCT) guided treatment interval failed to be extended to 6 weeks intervals in a treat and extend regimen.

Objectives: The primary objective is to evaluate the mean maximum recurrence-free treatment interval (Imax in weeks) with aflibercept treatment during the 24 months study peroid (for explanation see section Objectives). The individual maximum recurrence-free treatment interval (in weeks) at 24 weeks is defined as the maximum extension interval which is reached during the study follow-up period without showing any CNV activity (any intra-or subretinal fluid at OCT or new retinal hemorrhage). This measure reflects the duration of aflibercept effect in these lesions with limited response to ranibizumab. Key secondary Outcome Measures are mean changes in BCVA score at 24 weeks from baseline (Δ BCVAscore), mean changes in CRT (µm) at 24 weeks from baseline (Δ CRT), mean number of treatments needed during the 24 weeks study follow-up, number of participants with adverse events and serious adverse events (for further outcome measures see section Objectives).

Population: This outpatient study population will consist of a representative group of 33 male and female patients ≥ 50 years of age. The study population will include patients with subfoveal CNV secondary to AMD and being pre-treated with intravitreal ranibizumab in a treat and extend regimen and failed to be extended to 6-weeks intervals without showing CNV activity (for further information see section Criteria).

Interventions: 1-arm interventional study with 2mg aflibercept intravitreally up to 4-weekly. The first treatment interval with aflibercept will be 4 weeks and corresponding to the treat and extend regime intervals will be increased in 2-weeks-steps as long as no CNV activity (any intra-or subretinal fluid at OCT or new retinal hemorrhage) occurs. In case of occuring CNV activity the interval is shortened by 4 weeks with a minimum treatment interval of 4 weeks.


Condition or disease Intervention/treatment Phase
Neovascular Age-related Macular Degeneration Drug: aflibercept 2mg Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intravitreal Aflibercept (VEGF Trap-Eye) in Neovascular Age-related Macular Degeneration With Limited Response to Ranibizumab
Study Start Date : May 2013
Actual Primary Completion Date : May 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
aflibercept 2mg
Aflibercept 2mg (Eylea) is intravitreally applied. The first treatment interval with aflibercept will be 4 weeks and corresponding to the treat and extend regime intervals will be increased in 2-weeks-steps.
Drug: aflibercept 2mg
Aflibercept 2mg (Eylea) is intravitreally applied. The first treatment interval with aflibercept will be 4 weeks and corresponding to the treat and extend regime intervals will be increased in 2-weeks-steps.
Other Name: Eylea 2mg




Primary Outcome Measures :
  1. mean maximum recurrence-free treatment interval (Imax in weeks) with aflibercept treatment during the 24 months study peroid [ Time Frame: 24 weeks ]
    All eligible patients have to show a maximum treatment interval with ranibizumab (pre-study period) of 4 weeks (failed to be extended to 6 weeks, see Inclusion criteria), meaning that the mean maximum treatment interval at baseline is 4 weeks. During the study the treatment intervals with aflibercept will be increased in 2-weeks steps corresponding to the treat and extend regime (see Study design). The individual maximum recurrence-free treatment interval (in weeks) at 24 weeks is defined as the maximum extension interval which is reached during the study follow-up period without showing any CNV activity (any intra-or subretinal fluid at OCT or new retinal hemorrhage). This measure reflects the duration of aflibercept effect in these lesions with limited response to ranibizumab.


Secondary Outcome Measures :
  1. mean changes in BCVA score at 24 weeks compared to baseline (Δ BCVAscore=BCVAscore 24 weeks - BCVAscore Baseline) [ Time Frame: 24 weeks ]
    changes in BCVA score from Baseline to 24weeks

  2. mean changes in CRT (central retinal thickness; in µm) at 24 weeks compared to baseline (Δ CRT=CRT 24 weeks - CRT Baseline) [ Time Frame: 24 weeks ]
    changes from the CRT from Baseline to 24weeks

  3. percentage of patients with a maximum recurrence-free treatment interval of more than 4 weeks at 24 weeks [ Time Frame: 24 weeks ]
    percentage of patients have to show a Maximum recurrence

  4. mean number of treatments needed during the 24 weeks study follow-up [ Time Frame: 24 weeks ]
    number of treatments needed during the 24 weeks study

  5. percentage of lesions showing incidence of fluorescein leakage at baseline and 24 weeks. [ Time Frame: 24 weeks ]
    percentage of lesions showing incidence of fluorescein leakage from baseline to week 24

  6. mean change in total lesion area at 24 weeks compared to baseline (ΔTotalArea=TotalArea 24weeks - TotalArea Baseline) [ Time Frame: 24 weeks ]
    changes in total lesion area from Baseline to 24weeks

  7. mean change in area of leakage from CNV at 24 weeks compared to baseline (ΔLeakageArea=LeakageArea 24weeks - LeakageArea Baseline) [ Time Frame: 24 weeks ]
    change in area of leakage from CNV from baseline to week 24

  8. change of quality of life scores (VFQ-25, EQ 5D) from baseline to 24 weeks. [ Time Frame: 24 weeks ]
    changes of VFQ-25 questionaire from Baseline to 24weeks

  9. number of participants with adverse events (not fullfilling the criteria of serious adverse events) as a measure of safety and tolerability of up to 4weekly dosing of aflibercept in CNV due to AMD [ Time Frame: 24 weeks ]
    number of AEs from Baseline to week 24

  10. number of participants with serious adverse events as a measure of safety and tolerability of up to 4weekly dosing of aflibercept in CNV due to AMD [ Time Frame: 24 weeks ]
    number of SAEs from Baseline to week 24



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Male or female patients ≥ 50 years of age.
  • Active subfoveal CNV secondary to AMD, including those with predominantly classic, minimally classic or occult lesions with no classic component.
  • Pre-treatment with intravitreal ranibizumab in a treat and extend regimen with 2-weeks steps similar to the treat and extend regimen used in this study (see Study design) and failing to be extended to 6-weeks intervals without showing CNV activity (at least 2 attempts to extend from 4 to 6 weeks).
  • Evidence that CNV extends under the geometric center of the foveal avascular zone.
  • The total area of CNV (including all components) encompassed within the lesion must be ≥ 50% of the total lesion area.
  • The total lesion area ≤ 12 disc areas for minimally classic or occult with no classic component and ≤ 9 disc areas (5400µm) in greatest linear dimension with predominantly classic lesions.
  • BCVAscore of at least 23 letters (20/320) in the study eye using ETDRS charts.
  • Willing and able to give written informed consent according to legal requirements, and have signed the consent form prior to initiation of any study procedure including withdrawal from exclusionary medications for the purpose of this study.
  • Willing and able to comply with study procedures.

Exclusion criteria

  • Subretinal hemorrhage in the study eye involving the center of the fovea, if the size of the hemorrhage is ≥ 50% of the total lesion area or ≥ 1 disc area.
  • Presence of a retinal pigment epithelial tear or significant fibrosis involving the fovea in the study eye.
  • Angioid streaks or precursors of CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, pathologic myopia.
  • Concurrent disease in the study eye that could compromise visual acuity or require medical/surgical intervention during the study period.
  • Vitreous hemorrhage or history of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye.
  • Active intraocular inflammation in the study eye.
  • Any active infection involving ocular adnexa including infectious conjunctivitis, keratitis, scleritis, endophthalmitis, as well as idiopathic or autoimmune-associated uveitis in either eye.
  • History of uncontrolled glaucoma in the study eye (intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication).
  • Aphakia with absence of the posterior capsule in the study eye.
  • Prior treatment in the study eye with external-beam radiation therapy, subfoveal focal laser photocoagulation, vitrectomy, transpupillary thermotherapy.
  • History of submacular surgery or other surgical intervention for AMD in the study eye, glaucoma filtration surgery, corneal transplant surgery.
  • Extraction of cataract with phacoemulsification within 3 months preceding Baseline, or a history of post-operative complications within the last 12 months preceding Baseline in the study eye.
  • Use of other investigational drugs at the time of baseline, or within 30 days or 5 half- lives of baseline, whichever is longer (excluding vitamins + minerals).
  • Previous violation of the posterior capsule in the study eye unless as a result of YAG posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.
  • History of other disease, metabolic dysfunction, examination finding, or clinical laboratory finding giving reasonable suspicion of a disease/condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications.
  • Pregnant or nursing (lactating) women. Pregnancy is defined as the state after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>5 mIU/ml).
  • History of hypersensitivity/allergy to fluorescein.
  • Inability to obtain OCTs, fundus photographs, fluorescein angiograms of sufficient quality.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02309281


Sponsors and Collaborators
Vista Klinik
Bayer
Investigators
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Principal Investigator: Katja Hatz, MD Vista Klinik Binningen

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Responsible Party: Dr. med. Katja Hatz, Prof., Vista Klinik
ClinicalTrials.gov Identifier: NCT02309281     History of Changes
Other Study ID Numbers: Eylea1
First Posted: December 5, 2014    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
Keywords provided by Dr. med. Katja Hatz, Vista Klinik:
Eylea
Additional relevant MeSH terms:
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Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents