Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Three Different Aflibercept Regimens in Subjects With Diabetic Macular Edema (DME) (VIOLET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02818998
Recruitment Status : Completed
First Posted : June 30, 2016
Results First Posted : December 4, 2019
Last Update Posted : July 31, 2020
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
To evaluate the efficacy of long-term treatment with 2 mg aflibercept via different intravitreal (IVT) treatment regimens to participants with DME pretreated with 2 mg aflibercept every 8 weeks after 5 initial monthly injections for approximately 1 year or more (according to the EU label for the first year of treatment)

Condition or disease Intervention/treatment Phase
Macular Edema Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 463 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, Active-controlled, Parallel-group, Phase-3b Study of the Efficacy, Safety, and Tolerability of Three Different Treatment Regimens of 2 mg Aflibercept Administered by Intravitreal Injections to Subjects With Diabetic Macular Edema (DME)
Actual Study Start Date : November 16, 2016
Actual Primary Completion Date : November 13, 2018
Actual Study Completion Date : September 24, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Experimental: Aflibercept 2 mg fixed
Participants received fixed dosing of 2 mg aflibercept at injection intervals of 8 weeks
Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Experimental: Aflibercept 2 mg flexible
Participants received flexible dosing of 2 mg aflibercept at injection intervals of ≥8 week
Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Experimental: Aflibercept 2 mg PRN
Participants received monthly monitoring with 2 mg aflibercept injection pro re nata (PRN, as needed)
Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)



Primary Outcome Measures :
  1. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52 [ Time Frame: From baseline to Week 52 ]
    Best Corrected Visual Acuity (BCVA) was measured in the study eye by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. The ETDRS chart includes 70 letters in total and the letter score ranges from 0 to 100. More letters read correctly results in a higher letter score, which represents better visual acuity.


Secondary Outcome Measures :
  1. Mean Change From Baseline in Central Retinal Thickness (CRT) at Week 52 [ Time Frame: From baseline to week 52 ]
    Central Retinal Thickness (CRT) was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).

  2. Number of Participants With Categorized Changes From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52 [ Time Frame: From baseline to week 52 ]
    Best Corrected Visual Acuity (BCVA) was measured in the study eye by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. The ETDRS chart includes 70 letters in total and the letter score ranges from 0 to 100. More letters read correctly results in a higher letter score, which represents better visual acuity

  3. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 100 [ Time Frame: From baseline to Week 100 ]
    Best Corrected Visual Acuity (BCVA) was measured in the study eye by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. The ETDRS chart includes 70 letters in total and the letter score ranges from 0 to 100. More letters read correctly results in a higher letter score, which represents better visual acuity.

  4. Mean Change From Baseline in Central Retinal Thickness (CRT) at Week 100 [ Time Frame: From baseline to Week 100 ]
    Central Retinal Thickness (CRT) was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).

  5. Number of Participants With Categorized Changes From Baseline in Best Corrected Visual Acuity (BCVA) at Week 100 [ Time Frame: From baseline to Week 100 ]
    Best Corrected Visual Acuity (BCVA) was measured in the study eye by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. The ETDRS chart includes 70 letters in total and the letter score ranges from 0 to 100. More letters read correctly results in a higher letter score, which represents better visual acuity

  6. Number of Participants With Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to Week 100 ]
    AEs that started after the first application of aflibercept under this protocol until 30 days after the last dose of study drug administration



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

The subject's history of aflibercept treatment met all of the following:

  • Treatment in the study eye was initiated with five monthly (-1 week /+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed and documented.
  • Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks (one exception was allowed).
  • The interval between the last 2 pre-study injections was ≥ 8 weeks, and visual and anatomic outcomes had been stable over this interval.
  • The subject received the last intravitreal (IVT) injection of aflibercept in the study eye 8 weeks (±10 days) before the first planned treatment /randomization in this study.
  • Total prior treatment duration with aflibercept (i.e. from first aflibercept treatment ever to enrollment into this study) was 1 year or longer.

To be met at initiation of pre-study aflibercept treatment:

  • Type 1 or 2 diabetes mellitus (DM)
  • Diagnosis of diabetic macular edema (DME) secondary to DM involving the center of the macula (defined as the area of the center subfield on optical coherence tomography [OCT]) in the study eye
  • Decrease in vision determined to be primarily the result of DME in the study eye
  • Best corrected visual acuity (BCVA) in the study eye of Early Treatment Diabetic Retinopathy Study (ETDRS) letter score 73 to 24

Exclusion Criteria:

At initiation of pre-study aflibercept treatment:

- Previous treatment with anti-angiogenic drugs in study eye (e.g., pegaptanib sodium, bevacizumab, ranibizumab, or aflibercept) within the last 12 weeks before initiation of aflibercept pre-study treatment

At initiation of pre-study aflibercept treatment, screening for this study, and baseline for this study:

  • Prior treatment of the study eye with long acting steroids, either periocular or intraocular, in the preceding 120 days or Iluvien intravitreal implant at any time
  • Active proliferative diabetic retinopathy, current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye
  • Cataract surgery or any other intraocular surgery within 90 days of aflibercept treatment in the study eye
  • Ocular inflammation (including trace or above) or history of uveitis in the study eye
  • Structural damage to the center of the macula in the study eye that was likely to preclude improvement in BCVA following the resolution of macular edema including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia or organized hard exudates
  • Concurrent disease in the study eye, other than DME, that could compromise visual acuity, require medical or surgical intervention during the study period, or could confound interpretation of the results (including advanced glaucoma, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
  • Uncontrolled DM as defined by hemoglobin (Hb) A1c > 12.0% at screening and baseline for this study
  • Any ocular or periocular infection in the preceding 4 weeks in either eye
  • History of either cerebral vascular accident and/or myocardial infarction within 180 days before aflibercept treatment

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): NCT02818998


Locations
Show Show 64 study locations
Sponsors and Collaborators
Bayer
Investigators
Layout table for investigator information
Study Director: Bayer Study Director Bayer
  Study Documents (Full-Text)

Documents provided by Bayer:
Study Protocol  [PDF] December 7, 2015
Statistical Analysis Plan  [PDF] November 8, 2018

Additional Information:
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02818998    
Other Study ID Numbers: 17613
2014-004938-25 ( EudraCT Number )
First Posted: June 30, 2016    Key Record Dates
Results First Posted: December 4, 2019
Last Update Posted: July 31, 2020
Last Verified: July 2020

Layout table for additional information
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Bayer:
Diabetic macular edema
DME
Additional relevant MeSH terms:
Layout table for MeSH terms
Macular Edema
Edema
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases