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Macular EdemaPhase 3VIOLETNCT02818998

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

A Phase 3 study testing Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) in people with Macular Edema, run by Bayer at 64 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Macular Edema
What is being tested?
Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
463 participants
Where
64 sitesin 14 countries
Study dates
16 Nov 2016to 24 Sep 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

64 sites in 14 countries.

64 sites in 14 countries

Italy9 sites

  • Study site

    Cagliari, Sardinia, 09124

  • Study site

    Florence, Tuscany, 50134

  • Study site

    Genoa, Liguria, 16132

  • Study site

    Milan, Lombardy, 20122

  • Study site

    Milan, Lombardy, 20132

  • Study site

    Padova, Veneto, 35128

  • Study site

    Rome, Lazio, 00133

  • Study site

    Sassari, Sardinia, 07100

  • Study site

    Turin, Piedmont, 10122

Other trials in Italy

Poland9 sites

  • Study site

    Bydgoszcz, 85-631

  • Study site

    Gdansk, 80-809

  • Study site

    Katowice, 40-594

  • Study site

    Krakow, 31-501

  • Study site

    Lodz, 91-134

  • Study site

    Lublin, 20-081

  • Study site

    Poznan, 61-285

  • Study site

    Warsaw, 01-013

  • Study site

    Warsaw, 04-141

Other trials in Poland

Germany7 sites

  • Study site

    Bonn, North Rhine-Westphalia, 53105

  • Study site

    Cologne, North Rhine-Westphalia, 50924

  • Study site

    Darmstadt, Hesse, 64297

  • Study site

    Dresden, Saxony, 01307

  • Study site

    Frankfurt am Main, Hesse, 60596

  • Study site

    Göttingen, Lower Saxony, 37075

  • Study site

    Marburg, Hesse, 35043

Other trials in Germany

Spain6 sites

  • Study site

    Albacete, 02006

  • Study site

    Barcelona, 08035

  • Study site

    Barcelona, 08036

  • Study site

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Study site

    Sant Cugat Del Vallés, Barcelona, 08195

  • Study site

    Valencia, 46014

Other trials in Spain

Canada5 sites

  • Study site

    Halifax, Nova Scotia, B3H 2Y9

  • Study site

    Mississauga, Ontario, L4W 1W9

  • Study site

    Montreal, Quebec, H4P 2S4

  • Study site

    Sherbrooke, Quebec, J1G 2V4

  • Study site

    Toronto, Ontario, M3C 0G9

Other trials in Canada

Hungary5 sites

  • Study site

    Budapest, 1085

  • Study site

    Budapest, 1106

  • Study site

    Budapest, 1133

  • Study site

    Debrecen, 4032

  • Study site

    Pécs, 7621

Other trials in Hungary

Portugal5 sites

  • Study site

    Coimbra, 3000-548

  • Study site

    Leiria, 2410-197

  • Study site

    Lisbon, 1649-035

  • Study site

    Porto, 4200-319

  • Study site

    Vila Franca de Xira, Lisbon District, 2600-178

Other trials in Portugal

Slovakia5 sites

  • Study site

    Bratislava, 826 06

  • Study site

    Bratislava, 851 07

  • Study site

    Nitra, 949 01

  • Study site

    Žilina, 01207

  • Study site

    Zvolen, 960 01

Other trials in Slovakia

United Kingdom4 sites

  • Study site

    Leeds, West Yorkshire, LS9 7TF

  • Study site

    London, EC1V 2PD

  • Study site

    Southampton, Hampshire, SO16 6YD

  • Study site

    Sunderland, Tyne and Wear, SR2 9HP

Other trials in United Kingdom

Austria2 sites

  • Study site

    Graz, Styria, 8036

  • Study site

    Vienna, 1090

Other trials in Austria

Czechia2 sites

  • Study site

    Hradec Králové, 500 05

  • Study site

    Prague, 100 34

Other trials in Czechia

Lithuania2 sites

  • Study site

    Kaunas, LT-50009

  • Study site

    Vilnius, LT-08661

Other trials in Lithuania

Switzerland2 sites

  • Study site

    Bern

  • Study site

    Geneva, 1204

Other trials in Switzerland

France1 site

  • Study site

    Créteil, 94010

Other trials in France

About this study

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)

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)

Conditions
Macular Edema
Being tested
Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Keywords
Diabetic macular edema, DME
Medical subject headings
Macular Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)Drug

Study groups in NCT02818998
Study groupRoleWhat they receive
Aflibercept 2 mg fixedExperimentalParticipants received fixed dosing of 2 mg aflibercept at injection intervals of 8 weeks
Receives: Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Aflibercept 2 mg flexibleExperimentalParticipants received flexible dosing of 2 mg aflibercept at injection intervals of ≥8 week
Receives: Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Aflibercept 2 mg PRNExperimentalParticipants received monthly monitoring with 2 mg aflibercept injection pro re nata (PRN, as needed)
Receives: Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at 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.

    Measured: From baseline to Week 52

Secondary outcomes (6)

  1. Mean Change From Baseline in Central Retinal Thickness (CRT) at Week 52

    Central Retinal Thickness (CRT) was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).

    Measured: From baseline to week 52

  2. Number of Participants With Categorized Changes From Baseline in Best Corrected Visual Acuity (BCVA) at 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

    Measured: From baseline to week 52

  3. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at 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.

    Measured: From baseline to Week 100

  4. Mean Change From Baseline in Central Retinal Thickness (CRT) at Week 100

    Central Retinal Thickness (CRT) was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).

    Measured: From baseline to Week 100

  5. Number of Participants With Categorized Changes From Baseline in Best Corrected Visual Acuity (BCVA) at 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

    Measured: From baseline to Week 100

  6. Number of Participants With Treatment-emergent Adverse Event (TEAE)

    AEs that started after the first application of aflibercept under this protocol until 30 days after the last dose of study drug administration

    Measured: Up to Week 100

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2016 (estimated)
  2. Study start16 Nov 2016
  3. Primary completion13 Nov 2018
  4. Study completion24 Sep 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
463 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02818998
Sponsor's protocol ID
17613
Other IDs
2014-004938-25, 2014
Acronym
VIOLET
Status last verified
Jul 2020
First submitted
28 Jun 2016
Last updated
31 Jul 2020
Data monitoring committee
No
FDA-regulated device
No

Publications

  • Garweg JG, Stefanickova J, Hoyng C, Niesen T, Schmelter T, Leal S, Sivaprasad S; VIOLET Investigators. Dosing Regimens of Intravitreal Aflibercept for Diabetic Macular Edema Beyond the First Year: VIOLET, a Prospective Randomized Trial. Adv Ther. 2022 Jun;39(6):2701-2716. doi: 10.1007/s12325-022-02119-z. Epub 2022 Apr 12.

    PubMed 35412227

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) in people with Macular Edema, run by Bayer at 64 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in Italy, Poland, Germany, Spain, Canada and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52 (time frame: From baseline to Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02818998, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.

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