Macular Edema, DiabeticPhase 4VIBIMNCT02788877
Treat-and-extend Regimen of Aflibercept in Diabetic Macular Edema (VIBIM Study)
A Phase 4 study testing aflibercept in people with Macular Edema, Diabetic, run by Pusan National University Hospital at 8 sites in South Korea.
Trial summary
Efficacy of Treat-and-extend regimen (TER) using aflibercept in diabetic macular edema (DME) will be evaluated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Macular Edema, Diabetic
- What is being tested?
- aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 8 sitesSouth Korea
- Study dates
- 10 Apr 2016to Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Type I or II diabetes older than 18 years old
- Patients with DME secondary to diabetes mellitus involving the center of the macula (defined as CSMT >= 300μm measured using OCT) in the study eye.
- Decreased visual acuity to 20/40 - 20/300 to be primarily the results of DME in the study eye.
- Willing and able to comply with clinic visits and study-related procedures, and provide a signed informed consent form.
Who cannot join
- History of vitreoretinal surgery including scleral buckling in the study eye.
- Laser photocoagulation (panretinal or macular) in the study eye within 90 days of day 1.
- More than two previous macular laser treatments in the study eye.
- Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of day 1.
- Previous treatment with anti-angiogenic drugs in the study eye within 90 days of day 1.
- Active proliferative diabetic retinopathy in the study eye.
Show all 30Show fewer
- History of idiopathic or autoimmune uveitis in the study eye.
- Cataract surgery within 90 days before day 1 in the study eye.
- Aphakia in the study eye.
- Yttrium-aluminium-garnet capsulotomy in the study eye within 30 days before day 1.
- Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or on OCT that is thought to affect central vision.
- Current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye.
- Structural damage to the center of the macula in the study eye that is likely to preclude improvement in best-corrected visual acuity (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.
- Evidence of infection including infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye.
- Uncontrolled glaucoma in the study eye (>25mmHg) or filtration surgery and/or valve surgery for glaucoma in the past on the study eye.
- Myopia of a spherical equivalent prior to any possible refractive or cataract surgery of ≥ -8 diopters.
- Concurrent disease in the study eye, other than DME, that could compromise VA, require medical or surgical intervention during the study period, or could confound interpretation of the results (including retinal vascular occlusion retinal detachment, macular hole, or choroidal neovascularization of any cause).
- Ocular media of insufficient quality to obtain fundus and OCT images.
- Current treatment for a serious systemic infection.
- Administration of systemic anti-angiogenic agents within 180 days before day 1.
- Uncontrolled diabetes mellitus in the opinion of the investigator (VISTA) or as defined by hemoglobin A1c >12%.
- Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic > 95 mmHg while patient is sitting).
- History of either cerebral vascular accident and/or myocardial infarction within 180 days prior to day 1.
- Renal failure requiring dialysis or renal transplant.
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, might affect interpretation of the results of the study, or renders the patient at high risk for treatment complications.
- Pregnant or breast-feeding women.
- Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study.
- Allergy to fluorescein.
- Patients with hypersensitivity to study drug or excipients.
- Participation in an investigational study within 30 days prior to screening visit that involved treatment with any drug (excluding vitamins and minerals) or device.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
South Korea8 sites
Gospel Hospital
Busan, 602-702
Pusan National University Hospital
Busan, 602-739
Haeundae Paik Hospital
Busan, 612-030
Busan Paik Hospital
Busan, 614-735
Yeungnam University Medical Center
Daegu, 705-717
Keimyung University Dongsan Medical Center
Daegu
Kyungpook National University Hospital
Daegu
Gyeongsang National University Hospital
Jinju, Gyeongsangnam-do, 660-702
About this study
Official title: Single Arm, Single Dose Clinical Study to Investigate Efficacy of Treat-and-Extend Regimen of Intravitreal Aflibercept Injection in Diabetic Macular Edema
Efficacy of Treat-and-extend regimen (TER) using aflibercept in diabetic macular edema (DME) will be evaluated.
Read the detailed description
Efficacy of aflibercept for diabetic macular edema was demonstrated in the phase III, VIVID and VISTA studies. In these studies, aflibercept was injected using the fixed dosing regimen that an intravitreal injection was performed 5 times every 4 weeks and then every 8 weeks. Although the efficacy was comparable to that of ranibizumab injected every 4 weeks, continuous visits and treatments account for quite a burden. TER is regarded as a alternative regimen that may reduce visit and treatment numbers for age-related macular degeneration. TER is a variable dosing regimen that an injection interval is adjusted based on the treatment response. The aim of this study is to evaluate efficacy of TER using aflibercept for DME, by assessing changes of visual acuity at 104 weeks compared to baseline.
- Conditions
- Macular Edema, Diabetic
- Being tested
- aflibercept
- Medical subject headings
- Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
afliberceptDrug
Also called Eylea, VEGF Trap-Eye
Aflibercept 2mg is injected into the vitreous cavity through the pars plana using 30 gauge needle-attached syringe.
| Study group | Role | What they receive |
|---|---|---|
| treat-and-extend | Experimental | Aflibercept 2mg is injected into the vitreous cavity. An injection is given every 4 weeks five times and then the Treat-and-Extend process begins. If 1mm central subfield macular thickness (CSMT) improved (10% or more reduction) compared to the previous visit, the next treatment will be performed at the same interval. If CSMT is maintained (less than 10% changes), the next interval will be extended by two weeks (up to 12 weeks). If CSMT is worsened (10% or more increase), the next interval will be shortened by two weeks (minimum 4 weeks). If CSMT is stable two times at 12 weeks-interval, the injection will be deferred, and the next visit will be 8 weeks later. These process will be continued for 2 years. Receives: Drug: aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in visual acuity from baseline to 104 weeks
Visual acuity is assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Visual acuity of 85 letters is equivalent to 20/20. Higher scores represents better functioning.
Measured: baseline and 104 weeks
Secondary outcomes (7)
Changes in visual acuity from baseline to 52 weeks
Visual acuity is assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Visual acuity of 85 letters is equivalent to 20/20. Higher scores represents better functioning.
Measured: baseline and 52 weeks
Changes in CSMT from baseline to 104 weeks
CSMT is central 1mm thickness of the macula measured using spectral-domain optical coherence tomography (OCT). Normal thickness is around 250μm. Increased CSMT is regarded as presence of macular edema.
Measured: baseline and 104 weeks
Number of injections for 52 and 104 weeks
How many injections are performed from baseline to 52 and 104 weeks.
Measured: 52 and 104 weeks
Injection interval
The interval is calculated for the next visit based on the treatment response. The range is between 4 and 12 weeks.
Measured: 52 and 104 weeks.
Percentage of patients with injection interval of 12 weeks or more
Patients whose injection interval is extended to 12 weeks more include the patients that the next visit was calculated as 12 weeks and those that the injection was deferred in the previous visit.
Measured: 104 weeks.
Percentage of patients that visual acuity increased 15 letters or more
Visual acuity was assessed using ETDRS chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Higher scores represents better functioning. Percentage of patients whose visual acuity increased 15 letters or more compared to baseline will be calculated.
Measured: baseline, 52 and 104 weeks.
Percentage of Patients With Visual Acuity >=20/40
Visual acuity was assessed using ETDRS chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Higher scores represents better functioning. Percentage of patients with visual acuity 70 ETDRS letters (equivalent to 20/40) or better was calculated.
Measured: 52 and 104 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2016 (estimated)
- Study start10 Apr 2016
- Primary completionSep 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Macular Edema, DiabeticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pusan National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, Ji Eun Lee, Pusan National University Hospital
- Investigators
- Jae Pil Shin, MD, PhD, Study director, Kyungbuk National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02788877
- Sponsor's protocol ID
- 20160043
- Acronym
- VIBIM
- Status last verified
- Feb 2019
- First submitted
- 27 May 2016
- Last updated
- 1 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031.
PubMed 21459215Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, Midena E, Kaiser PK, Terasaki H, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Brown DM. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j.ophtha.2014.05.006. Epub 2014 Jul 8.
PubMed 25012934Gupta OP, Shienbaum G, Patel AH, Fecarotta C, Kaiser RS, Regillo CD. A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology. 2010 Nov;117(11):2134-40. doi: 10.1016/j.ophtha.2010.02.032. Epub 2010 Jul 1.
PubMed 20591490CATT Research Group; Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011 May 19;364(20):1897-908. doi: 10.1056/NEJMoa1102673. Epub 2011 Apr 28.
PubMed 21526923Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.
PubMed 25692915
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm, Single Dose Clinical Study to Investigate Efficacy of Treat-and-Extend Regimen of Intravitreal Aflibercept Injection in Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT02788877
- Acronym / sponsor ID
- VIBIM / 20160043
- Conditions
- Macular Edema, Diabetic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Pusan National University HospitalUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 10 Apr 2016 (actual)
- Primary completion
- Sep 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 2 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Efficacy of Treat-and-extend regimen (TER) using aflibercept in diabetic macular edema (DME) will be evaluated.
Detailed description
Efficacy of aflibercept for diabetic macular edema was demonstrated in the phase III, VIVID and VISTA studies. In these studies, aflibercept was injected using the fixed dosing regimen that an intravitreal injection was performed 5 times every 4 weeks and then every 8 weeks. Although the efficacy was comparable to that of ranibizumab injected every 4 weeks, continuous visits and treatments account for quite a burden. TER is regarded as a alternative regimen that may reduce visit and treatment numbers for age-related macular degeneration. TER is a variable dosing regimen that an injection interval is adjusted based on the treatment response. The aim of this study is to evaluate efficacy of TER using aflibercept for DME, by assessing changes of visual acuity at 104 weeks compared to baseline.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treat-and-extend | Experimental | Drug: afliberceptAflibercept 2mg is injected into the vitreous cavity. An injection is given every 4 weeks five times and then the Treat-and-Extend process begins. If 1mm central subfield macular thickness (CSMT) improved (10% or more reduction) compared to the previous visit, the next treatment will be performed at the same interval. If CSMT is maintained (less than 10% changes), the next interval will be extended by two weeks (up to 12 weeks). If CSMT is worsened (10% or more increase), the next interval will be shortened by two weeks (minimum 4 weeks). If CSMT is stable two times at 12 weeks-interval, the injection will be deferred, and the next visit will be 8 weeks later. These process will be continued for 2 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Type I or II diabetes older than 18 years old
- Patients with DME secondary to diabetes mellitus involving the center of the macula (defined as CSMT >= 300μm measured using OCT) in the study eye.
- Decreased visual acuity to 20/40 - 20/300 to be primarily the results of DME in the study eye.
- Willing and able to comply with clinic visits and study-related procedures, and provide a signed informed consent form.
Key exclusion criteria (30 listed)
- History of vitreoretinal surgery including scleral buckling in the study eye.
- Laser photocoagulation (panretinal or macular) in the study eye within 90 days of day 1.
- More than two previous macular laser treatments in the study eye.
- Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of day 1.
- Previous treatment with anti-angiogenic drugs in the study eye within 90 days of day 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| afliberceptAlso: Eylea, VEGF Trap-EyeAflibercept 2mg is injected into the vitreous cavity through the pars plana using 30 gauge needle-attached syringe. | Drug | treat-and-extend |
Primary outcome
Changes in visual acuity from baseline to 104 weeks
Time frame: baseline and 104 weeks
Visual acuity is assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Visual acuity of 85 letters is equivalent to 20/20. Higher scores represents better functioning.
7 secondary outcomes
Changes in visual acuity from baseline to 52 weeks
Time frame: baseline and 52 weeks
Changes in CSMT from baseline to 104 weeks
Time frame: baseline and 104 weeks
Number of injections for 52 and 104 weeks
Time frame: 52 and 104 weeks
Injection interval
Time frame: 52 and 104 weeks.
Percentage of patients with injection interval of 12 weeks or more
Time frame: 104 weeks.
Percentage of patients that visual acuity increased 15 letters or more
Time frame: baseline, 52 and 104 weeks.
Percentage of Patients With Visual Acuity >=20/40
Time frame: 52 and 104 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2019.
- Background: PubMed 21459215Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031.
- Background: PubMed 25012934Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, Midena E, Kaiser PK, Terasaki H, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Brown DM. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j.ophtha.2014.05.006. Epub 2014 Jul 8.
- Background: PubMed 20591490Gupta OP, Shienbaum G, Patel AH, Fecarotta C, Kaiser RS, Regillo CD. A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology. 2010 Nov;117(11):2134-40. doi: 10.1016/j.ophtha.2010.02.032. Epub 2010 Jul 1.
- Background: PubMed 21526923CATT Research Group; Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011 May 19;364(20):1897-908. doi: 10.1056/NEJMoa1102673. Epub 2011 Apr 28.
- Background: PubMed 25692915Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jae Pil Shin, MD, PhD study director
Kyungbuk National University Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing aflibercept in people with Macular Edema, Diabetic, run by Pusan National University Hospital at 8 sites in South Korea.
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 4 inclusion and 30 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: status not confirmed, as of the sponsor's last update on 1 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in South Korea. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Changes in visual acuity from baseline to 104 weeks (time frame: baseline and 104 weeks). 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 NCT02788877, which also lists 5 linked publications.
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 1 Mar 2019.