Age Related Macular DegenerationNCT02218177
Intraocular Cytokines in Non-responders to Ranibizumab Treatment for Neovascular AMD
An observational study of Age Related Macular Degeneration, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
The purpose of this study is to evaluate the level of cytokines (which are small proteins important in cell signalling) in eye fluid (aqueous humour) in patients with wet age related macular degeneration patients who have been treated with an injection in the eye (intravitreal injection) with a drug called… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Age Related Macular Degeneration
- What is being tested?
- Aflibercept, Ranibizumab and Combination Photodynamic Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2014to Dec 2016
- Phase
- Observational
- 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
Study population: Study patients in the treatment group will be those greater than 50 years old, with age related macular degeneration, who are non-responder/ resistance to ranibizumab treatment. Control group will include patients who are responders to ranibizumab treatment.
Who may be able to join
- Age 50 years or more
- Ranibizumab resistance/poor responder patients in all AMD entities (typical AMD, PCV and RAP) who will be treated with intravitreous ranibizumab in combination with verteporfin photodynamic therapy
- Ranibizumab resistance/poor responder patients in all AMD entity (typical AMD, PCV and RAP) who will be treated with intravitreous aflibercept injection
- AMD patient who is good response to the treatment of ranibizumab (control group)
Who cannot join
- Any evidence of good response in treatment of ranibizumab,
- Uncooperative patients to intravitreal treatment
- Patients who have clinically active ocular inflammation
- Patients who have previous PDT treatment within 6 months
- Patient who previously have ocular treatment of immunosuppressive agent within 3 months
- Patient who previously have ocular treatment of steroid with in 3 months
- Patients who are currently on systemic treatment of anti-VEGF medication or immunosuppressive agents.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neovascular Age-related Macular Degeneration: Intraocular Inflammatory Cytokines in the Non-responder to Ranibizumab Treatment
The purpose of this study is to evaluate the level of cytokines (which are small proteins important in cell signalling) in eye fluid (aqueous humour) in patients with wet age related macular degeneration patients who have been treated with an injection in the eye (intravitreal injection) with a drug called ranibizumab. The level of cytokines will be compared between patients who have a good response to ranibizumab treatment and patients who are non-responsive to ranibizumab and need other forms of therapy. This knowledge will help for the future treatment and to potentially develop new medication for wet age-related macular degeneration.
Read the detailed description
In the treatment of CNV (Choroidal NeoVascularization) secondary from AMD (Age Related Macular Degeneration) by using ranibizumab, patients who are non-responders can be found in approximately 1-10% of treatments. Thus, failure of treatment can lead to loss of vision. Growth factors and cytokines, such as vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), interleukin 6 (IL-6) and placenta growth factor (PLGF) are known to play an important role in the development of CNV angiogenesis.
The rationale for conducting this study to compare VEGF, PEDF, IL-6 and PLGF cytokine levels in the aqueous humor of wet AMD and Polypoidal Choroidal Vasculopathy (PCV) patients who are poor responders to anti VEGF treatment and age-matched "good" responders to anti VEGF. Ranibizumab poor responders in AMD and PCV, who are treated with a combination of PDT/ranibizumab or intravitreous injection of aflibercept (Eyelea®, Regeneron Pharmaceuticals Inc. Tarrytown, NY, USA and Bayer, Basel, Switzerland) will be enrolled to the study. An aqueous humor sample will be obtained when patient receives intravitreal injection treatment and also at 1, 2 months follow up period. VEGF, PEDF,IL-6 and PLGF in aqueous will be analyzed and used to compare between the poor response group and age matched patient with good response to ranibizumab. Age, gender, visual acuity, central macular thickness by OCT, lesion size and fundus autofluorescence data will be collected and used to compare between these groups. Subgroup analysis of different treatment comparison with ranibizumab good responder group will be evaluated. Factors associated with the non-responders of ranibizumab will be analyzed.
Non-responders to ranibizumab treatment in AMD may have different levels and responses of inflammatory cytokines compared to the responder group. Understanding the pathogenesis and characteristic of this specific group of patients can help narrow down a specific choice of treatment and prevent the reduction of visual acuity of the patient. This study also helps identify factors associated to poor responders from ranibizumab treatment for wAMD.
- Conditions
- Age Related Macular Degeneration
- Being tested
- Aflibercept, Ranibizumab, Combination Photodynamic Therapy
- Keywords
- wet Age Related Macular Degeneration, Ranibizumab, Aflibercept, Combination Photodynamic Therapy, Cytokine analysis
- Medical subject headings
- Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfliberceptDrug
Also called Eylea (R)
anti-VEGF treatment for wet age related macular degeneration
RanibizumabDrug
Also called Lucentis
anti-VEGF treatment for wet age related macular degeneration
Combination Photodynamic TherapyProcedure or surgery
Use of cold laser with an intravitreal injection of dexamethasone to treat wet age related macular degeneration
| Study group | Role | What they receive |
|---|---|---|
| Non-responders receiving aflibercept therapy | Non-responders to ranibizumab who are now receiving aflibercept therapy Receives: Drug: Aflibercept | |
| Non-responders receiving PDT combo therapy | patients who are non-responders to ranibizumab who have been switched to combination photodynamic therapy (PDT) Receives: Procedure: Combination Photodynamic Therapy | |
| Responders to ranibizumab | Patients who are responders to ranibizumab and are continuing monthly injections. Receives: Drug: Ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aqueous Humour Cytokine Levels
Measured: At time of Intravitreal Injection
Secondary outcomes (5)
Demographic Data
Measured: At time of appointment
Number of anti-VEGF injections before developing non-responder characteristics
Measured: At time of appointment
History of Previous Treatment
Measured: At time of appointment
Optical Coherence Tomography (OCT) results
Measured: At time of appointment
Fluorescein Angiography Results and Indocyanine Green Angiography Results
Measured: At time of appointment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionAug 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Age Related Macular DegenerationStudies of the same condition, open and under way.
- More trials run by University Health Network, 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wai-Ching Lam, University Health Network, Toronto
- Investigators
- Wai-Ching Lam, MD, Principal investigator, Toronto Western Hospital, University Health Network, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02218177
- Sponsor's protocol ID
- VEGF wAMD cytokine study
- Status last verified
- Oct 2018
- First submitted
- 13 Aug 2014
- Last updated
- 11 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Pongsachareonnont P, Mak MYK, Hurst CP, Lam WC. Neovascular age-related macular degeneration: intraocular inflammatory cytokines in the poor responder to ranibizumab treatment. Clin Ophthalmol. 2018 Sep 26;12:1877-1885. doi: 10.2147/OPTH.S171636. eCollection 2018.
PubMed 30310267
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neovascular Age-related Macular Degeneration: Intraocular Inflammatory Cytokines in the Non-responder to Ranibizumab Treatment
- ClinicalTrials.gov ID
- NCT02218177
- Acronym / sponsor ID
- VEGF wAMD cytokine study
- Conditions
- Age Related Macular Degeneration
- Keywords
- wet Age Related Macular Degeneration, Ranibizumab, Aflibercept, Combination Photodynamic Therapy, Cytokine analysis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Aug 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 18 Aug 2014 (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.
The purpose of this study is to evaluate the level of cytokines (which are small proteins important in cell signalling) in eye fluid (aqueous humour) in patients with wet age related macular degeneration patients who have been treated with an injection in the eye (intravitreal injection) with a drug called ranibizumab. The level of cytokines will be compared between patients who have a good response to ranibizumab treatment and patients who are non-responsive to ranibizumab and need other forms of therapy. This knowledge will help for the future treatment and to potentially develop new medication for wet age-related macular degeneration.
Detailed description
In the treatment of CNV (Choroidal NeoVascularization) secondary from AMD (Age Related Macular Degeneration) by using ranibizumab, patients who are non-responders can be found in approximately 1-10% of treatments. Thus, failure of treatment can lead to loss of vision. Growth factors and cytokines, such as vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), interleukin 6 (IL-6) and placenta growth factor (PLGF) are known to play an important role in the development of CNV angiogenesis.
The rationale for conducting this study to compare VEGF, PEDF, IL-6 and PLGF cytokine levels in the aqueous humor of wet AMD and Polypoidal Choroidal Vasculopathy (PCV) patients who are poor responders to anti VEGF treatment and age-matched "good" responders to anti VEGF. Ranibizumab poor responders in AMD and PCV, who are treated with a combination of PDT/ranibizumab or intravitreous injection of aflibercept (Eyelea®, Regeneron Pharmaceuticals Inc. Tarrytown, NY, USA and Bayer, Basel, Switzerland) will be enrolled to the study. An aqueous humor sample will be obtained when patient receives intravitreal injection treatment and also at 1, 2 months follow up period. VEGF, PEDF,IL-6 and PLGF in aqueous will be analyzed and used to compare between the poor response group and age matched patient with good response to ranibizumab. Age, gender, visual acuity, central macular thickness by OCT, lesion size and fundus autofluorescence data will be collected and used to compare between these groups. Subgroup analysis of different treatment comparison with ranibizumab good responder group will be evaluated. Factors associated with the non-responders of ranibizumab will be analyzed.
Non-responders to ranibizumab treatment in AMD may have different levels and responses of inflammatory cytokines compared to the responder group. Understanding the pathogenesis and characteristic of this specific group of patients can help narrow down a specific choice of treatment and prevent the reduction of visual acuity of the patient. This study also helps identify factors associated to poor responders from ranibizumab treatment for wAMD.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Non-responders receiving aflibercept therapy | – | Drug: AfliberceptNon-responders to ranibizumab who are now receiving aflibercept therapy |
| Non-responders receiving PDT combo therapy | – | Procedure: Combination Photodynamic Therapypatients who are non-responders to ranibizumab who have been switched to combination photodynamic therapy (PDT) |
| Responders to ranibizumab | – | Drug: RanibizumabPatients who are responders to ranibizumab and are continuing monthly injections. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Study patients in the treatment group will be those greater than 50 years old, with age related macular degeneration, who are non-responder/ resistance to ranibizumab treatment. Control group will include patients who are responders to ranibizumab treatment.
Key inclusion criteria (4 listed)
- Age 50 years or more
- Ranibizumab resistance/poor responder patients in all AMD entities (typical AMD, PCV and RAP) who will be treated with intravitreous ranibizumab in combination with verteporfin photodynamic therapy
- Ranibizumab resistance/poor responder patients in all AMD entity (typical AMD, PCV and RAP) who will be treated with intravitreous aflibercept injection
- AMD patient who is good response to the treatment of ranibizumab (control group)
Key exclusion criteria (7 listed)
- Any evidence of good response in treatment of ranibizumab,
- Uncooperative patients to intravitreal treatment
- Patients who have clinically active ocular inflammation
- Patients who have previous PDT treatment within 6 months
- Patient who previously have ocular treatment of immunosuppressive agent within 3 months
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 (R)anti-VEGF treatment for wet age related macular degeneration | Drug | Non-responders receiving aflibercept therapy |
| RanibizumabAlso: Lucentisanti-VEGF treatment for wet age related macular degeneration | Drug | Responders to ranibizumab |
| Combination Photodynamic TherapyUse of cold laser with an intravitreal injection of dexamethasone to treat wet age related macular degeneration | Procedure or surgery | Non-responders receiving PDT combo therapy |
Primary outcome
Aqueous Humour Cytokine Levels
Time frame: At time of Intravitreal Injection
5 secondary outcomes
Demographic Data
Time frame: At time of appointment
Number of anti-VEGF injections before developing non-responder characteristics
Time frame: At time of appointment
History of Previous Treatment
Time frame: At time of appointment
Optical Coherence Tomography (OCT) results
Time frame: At time of appointment
Fluorescein Angiography Results and Indocyanine Green Angiography Results
Time frame: At time of appointment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2018.
- Derived from this study: PubMed 30310267Pongsachareonnont P, Mak MYK, Hurst CP, Lam WC. Neovascular age-related macular degeneration: intraocular inflammatory cytokines in the poor responder to ranibizumab treatment. Clin Ophthalmol. 2018 Sep 26;12:1877-1885. doi: 10.2147/OPTH.S171636. eCollection 2018.
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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.
Wai-Ching Lam, MD principal investigator
Toronto Western Hospital, University Health Network, University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Age Related Macular Degeneration, run by University Health Network, Toronto at 1 site 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 4 inclusion and 7 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 11 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Aqueous Humour Cytokine Levels (time frame: At time of Intravitreal Injection). 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 NCT02218177, 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 11 Oct 2018.