Age Related Macular DegenerationPhase 4COVARIANTNCT03056079
Cytokine and Visual Outcome Variations in Eyes Receiving Aflibercept
A Phase 4 study testing Intravitreal aflibercept in people with Age Related Macular Degeneration and Diabetic Macular Edema, run by Unity Health Toronto at 2 sites in Canada.
Trial summary
Objective: To determine the association between baseline aqueous cytokine levels and treatment intervals for patients under a variable dosing regimen with intravitreal aflibercept in patients with neovascular age-related macular degeneration (nAMD), macular edema secondary to retinal vein occlusion (RVO) and diabetic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Age Related Macular Degeneration, Diabetic Macular Edema, Retinal Vein Occlusion
- What is being tested?
- Intravitreal aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 2 sitesCanada
- Study dates
- 28 Feb 2017to 28 Feb 2024
- 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
- Diagnosis of active choroidal neovascularization secondary to AMD in the study eye
- Diagnosis of macular edema secondary to RVO: central macular thickness >310μm due to intraretinal or subretinal edema in the study eye as measured on OCT
- Diagnosis of DME with central macular thickness >310μm in the study eye as measured on OCT in patients with diabetes mellitus types 1 or 2
Who cannot join
- • Previous intravitreal drug injections in either eye within 6 months prior to study enrollment
- Visual acuity worse than counting fingers
- Patients with other macular pathologies causing structural changes to the retina
- Patients with large submacular hemorrhages or extensive fibrosis occupying the majority (>50%) of the lesion
- Intraocular surgery in the study eye 3 months prior to study enrollment
- Previous vitreoretinal surgery in the study eye
Show all 15Show fewer
- Previous photodynamic or macular photocoagulation therapy within the past 6 months in the study eye in patients with AMD
- Previous photocoagulation therapy within 6 months in the study eye or anticipated need for during the course of the study in patients with RVO
- Presence of active proliferative diabetic retinopathy or patients who have had pan-retinal photocoagulation within 6 months or patients where the need to pan-retinal photocoagulation is anticipated during the course of the study in patients with DME
- History of intraocular inflammation in the study eye
- Patients on systemic or topical anti-inflammatory or steroids medications
- Patients receiving dialysis for renal failure
- Known allergy to the study drug or fluorescein
- Patients who are pregnant
- Unwilling or unable to follow or comply with all study related procedures or to sign consent form
Trial locations and contacts
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Recruiting
Department of Ophthalmology, St Michael's Hospital
Toronto, Ontario, M5C 2T2
Rajeev H Muni, FRCSC
- Recruiting
Sunnybrook Health Sciences Centre
Toronto
Peter Kertes
About this study
Official title: Cytokine and Visual Outcome Variations in Eyes Receiving a Variable Dosing Aflibercept Treatment: The COVARIANT Study
Objective: To determine the association between baseline aqueous cytokine levels and treatment intervals for patients under a variable dosing regimen with intravitreal aflibercept in patients with neovascular age-related macular degeneration (nAMD), macular edema secondary to retinal vein occlusion (RVO) and diabetic macular edema (DME).
Methods: A prospective, single-centre study will be performed containing 3 sub-studies according to each study population: nAMD, macular edema secondary to RVO and DME. Inclusion criteria are: patients followed at St. Michael's Hospital with the diagnosis of nAMD, macular edema secondary to RVO or DME. Patients will be excluded if visual acuity is worse than counting fingers, with macular pathologies causing any structural changes to the retina, have received anti-VEGF injections or photocoagulation therapy 6 months prior to study, intraocular surgery 3 months prior to study, any history of vitreoretinal surgery or ocular inflammation in the study eye, use of systemic or topical anti-inflammatory or steroids, patients on dialysis for renal failure, allergy to the study drug or fluorescein, <18 years old, women who are pregnant. All patients will be treated with aflibercept intravitreal injections on a variable dosing regimen: Patients with DME will be examined monthly and receive mandatory injection for the first three months (baseline, weeks 4 and 8). Afterwards, they will continue to be seen monthly and the need for new injections will be decided upon the clinical findings at each visit. An anterior chamber (AC) tap will be done if an injection is required at the visit. Patients with nAMD and RVO will be examined monthly and receive mandatory injection for the first three months. From weeks 12 until 72 (month 18), the visits will be scheduled at increasing 2-weeks intervals based on the stability of the ocular condition and response to treatment. At each visit, an injection and AC tap will be performed. The maximum interval in between injections is 12 weeks. If the disease becomes unstable, the interval in between injections is shortened and, once it stabilizes, the treatment frequency is extended again. In all patients, baseline aqueous humour specimens will be obtained prior to the first aflibercept intravitreal injection and follow-up samples will be taken immediately prior to subsequent injections based on the treatment regimens for cytokine analysis in the end of the follow-up.
- Conditions
- Age Related Macular Degeneration, Diabetic Macular Edema, Retinal Vein Occlusion, Macular Edema
- Being tested
- Intravitreal aflibercept
- Keywords
- neovascular age related macular degeneration, diabetic macular edema, retinal vein occlusion, aflibercept, aqueous humor cytokine
- Medical subject headings
- Macular Degeneration, Retinal Vein Occlusion, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravitreal afliberceptDrug
Also called Eylea
Patients will receive intravitreal aflibercept on a variable dosing regimen and have aqueous humor sample obtained for cytokine analysis at every visit when an intravitreal injection is done.
| Study group | Role | What they receive |
|---|---|---|
| AMD/RVO/DME | Other | Patients presenting to St. Michael's Hospital retina clinic with neovascular AMD, macular edema secondary to retinal vein occlusion and diabetic macular edema treated with intravitreal aflibercept in a variable dosing regimen. Receives: Drug: Intravitreal aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Association between cytokine levels and optimal treatment interval
Optimal interval between injections based on aqueous cytokine levels
Measured: 18 months
Secondary outcomes (6)
Individualized aqueous cytokine curves relationship with treatment response
Aqueous cytokine curves for each patient based on the relationship between cytokine levels and treatment response
Measured: 18 months
Cytokine threshold level with visual and anatomic outcomes
Cytokine threshold level below which visual and anatomic outcomes are greatest
Measured: 18 months
Snellen BCVA change
To assess Snellen Best Corrected Visual Acuity (BCVA) change at months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period.
Measured: months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period.
ETDRS visual acuity change
Visual acuity (ETDRS) change at month 2 (at the third injection), at the visits closest to injection of months 6, 12 and 18.
Measured: month 2, at the visits closest to injection of months 6, 12 and 18.
Optical coherence tomography change
Anatomic OCT change (Macular Volume, Central Macular Thickness) at months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period.
Measured: months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period.
Average number of injections needed
Average number of injections needed in a variable dosing regimen protocol over an 18 months period.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2017
- Study start28 Feb 2017
- Primary completion28 Feb 2024 (estimated)
- Study completion28 Feb 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Age Related Macular DegenerationStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe sponsor's other registered studies.
- 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
- Model description
- This study will contain 3 populations of patients which will all receive aflibercept injections: one with neovascular age-related macular degeneration, other with diabetic macular edema and a third with macular edema secondary to retinal vein occlusion.
- Masking
- None (open label)
- Enrolment
- 168 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rajeev Muni, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03056079
- Sponsor's protocol ID
- COVARIANT
- Acronym
- COVARIANT
- Status last verified
- Apr 2021
- First submitted
- 1 Feb 2017
- Last updated
- 28 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cytokine and Visual Outcome Variations in Eyes Receiving a Variable Dosing Aflibercept Treatment: The COVARIANT Study
- ClinicalTrials.gov ID
- NCT03056079
- Acronym / sponsor ID
- COVARIANT / COVARIANT
- Conditions
- Age Related Macular Degeneration, Diabetic Macular Edema, Retinal Vein Occlusion, Macular Edema
- Keywords
- neovascular age related macular degeneration, diabetic macular edema, retinal vein occlusion, aflibercept, aqueous humor cytokine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 168 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 28 Feb 2017 (actual)
- Primary completion
- 28 Feb 2024 (estimated)
- Study completion
- 28 Feb 2024 (estimated)
- First posted
- 17 Feb 2017 (actual)
- 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.
Objective: To determine the association between baseline aqueous cytokine levels and treatment intervals for patients under a variable dosing regimen with intravitreal aflibercept in patients with neovascular age-related macular degeneration (nAMD), macular edema secondary to retinal vein occlusion (RVO) and diabetic macular edema (DME).
Methods: A prospective, single-centre study will be performed containing 3 sub-studies according to each study population: nAMD, macular edema secondary to RVO and DME. Inclusion criteria are: patients followed at St. Michael's Hospital with the diagnosis of nAMD, macular edema secondary to RVO or DME. Patients will be excluded if visual acuity is worse than counting fingers, with macular pathologies causing any structural changes to the retina, have received anti-VEGF injections or photocoagulation therapy 6 months prior to study, intraocular surgery 3 months prior to study, any history of vitreoretinal surgery or ocular inflammation in the study eye, use of systemic or topical anti-inflammatory or steroids, patients on dialysis for renal failure, allergy to the study drug or fluorescein, <18 years old, women who are pregnant. All patients will be treated with aflibercept intravitreal injections on a variable dosing regimen: Patients with DME will be examined monthly and receive mandatory injection for the first three months (baseline, weeks 4 and 8). Afterwards, they will continue to be seen monthly and the need for new injections will be decided upon the clinical findings at each visit. An anterior chamber (AC) tap will be done if an injection is required at the visit. Patients with nAMD and RVO will be examined monthly and receive mandatory injection for the first three months. From weeks 12 until 72 (month 18), the visits will be scheduled at increasing 2-weeks intervals based on the stability of the ocular condition and response to treatment. At each visit, an injection and AC tap will be performed. The maximum interval in between injections is 12 weeks. If the disease becomes unstable, the interval in between injections is shortened and, once it stabilizes, the treatment frequency is extended again. In all patients, baseline aqueous humour specimens will be obtained prior to the first aflibercept intravitreal injection and follow-up samples will be taken immediately prior to subsequent injections based on the treatment regimens for cytokine analysis in the end of the follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study will contain 3 populations of patients which will all receive aflibercept injections: one with neovascular age-related macular degeneration, other with diabetic macular edema and a third with macular edema secondary to retinal vein occlusion.
| Arm | Type | Receives |
|---|---|---|
| AMD/RVO/DME | Other | Drug: Intravitreal afliberceptPatients presenting to St. Michael's Hospital retina clinic with neovascular AMD, macular edema secondary to retinal vein occlusion and diabetic macular edema treated with intravitreal aflibercept in a variable dosing regimen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of active choroidal neovascularization secondary to AMD in the study eye
- Diagnosis of macular edema secondary to RVO: central macular thickness >310μm due to intraretinal or subretinal edema in the study eye as measured on OCT
- Diagnosis of DME with central macular thickness >310μm in the study eye as measured on OCT in patients with diabetes mellitus types 1 or 2
Key exclusion criteria (15 listed)
- • Previous intravitreal drug injections in either eye within 6 months prior to study enrollment
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 |
|---|---|---|
| Intravitreal afliberceptAlso: EyleaPatients will receive intravitreal aflibercept on a variable dosing regimen and have aqueous humor sample obtained for cytokine analysis at every visit when an intravitreal injection is done. | Drug | AMD/RVO/DME |
Primary outcome
Association between cytokine levels and optimal treatment interval
Time frame: 18 months
Optimal interval between injections based on aqueous cytokine levels
6 secondary outcomes
Individualized aqueous cytokine curves relationship with treatment response
Time frame: 18 months
Cytokine threshold level with visual and anatomic outcomes
Time frame: 18 months
Snellen BCVA change
Time frame: months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period.
ETDRS visual acuity change
Time frame: month 2, at the visits closest to injection of months 6, 12 and 18.
Optical coherence tomography change
Time frame: months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period.
Average number of injections needed
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2021.
- 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.
Rajeev Muni principal investigator
Unity Health Toronto
2 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 Intravitreal aflibercept in people with Age Related Macular Degeneration and Diabetic Macular Edema, run by Unity Health Toronto at 2 sites in Canada.
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 3 inclusion and 15 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 28 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
Contact Rajeev Muni (416-867-7411, rajeev.muni@utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association between cytokine levels and optimal treatment interval (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Apr 2021.