Macular Oedema, Retinitis Pigmentosa
Conditions
Keywords
Macular Oedema Retinitis Pigmentosa
Brief summary
The purpose of this study is to assess the safety and efficacy of intravitreal injections of Aflibercept (Eylea) in treating Cystoid Macula Oedema (CMO) in patients with underlying Retinitis Pigmentosa (RP).
Detailed description
This is a 17 month phase II therapeutic exploratory trial in Cystoid Macular Oedema (CMO) with underlying Retinitis Pigmentosa (RP). The study design is a prospective, open-label, interventional non-randomised trial. All patients enrolled in the study will receive intravitreal injections of Aflibercept (Eylea). There will be a 9 month recruitment window and patient participation will be for 12 months; 30 patients aged 16 years or older presenting in the Medical Retina and Genetics clinics at Moorfields Eye Hospital with Cystoid Macula Oedema (CMO) with underlying Retinitis Pigmentosa (RP) will be approached by the study team to discuss participation in the AMOUR study and be given a patient information leaflet. If patients decide to participate in the study they will be invited to the NIHR Moorfields Clinical Research Facility for a baseline screening where written informed consent will be given by the patient and various assessments will be performed to confirm eligibility. Patients enrolled in the study will receive intravitreal injections of 2mg of 40mg/ml of Aflibercept (Eylea) solution in the study eye. In the first three months, patients will receive a loading dose of Aflibercept (Eylea) with one injection every four weeks. After the first three months, treatment frequency will follow a treat and extend protocol for up to 12 months from date of study enrolment. Extension from 4 weekly to 6,8,10 and 12 week follow up will occur when there is no further reduction in macula fluid compared to the previous visit. Patients will receive a minimum of 5 injections before being deemed as non-responders to treatment. Imaging and assessments such as optical coherence tomography imaging, microperimetry and visual acuity will be used to assess response to treatment.
Interventions
DRUGAflibercept
2mg of 40mg/ml of Eylea Solution administered via intravitreal injection every four weeks for three months (loading dose), followed by a treat and extend protocol up to 12 months. Extension from monthly to 6, 8, 10 and 12 week follow up will occur where there is no reduction in macula oedema compared with the previous visit. Number of cycles; minimum of 5 injections and maximum of 13 injections per study eye.
Sponsors
Bayer
Moorfields Eye Hospital NHS Foundation Trust
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* CMO in association with RP * \> 16 years of age * Unilateral or Bilateral CMO (the worse eye only will be treated - defined as the eye with a greater central macular thickness (CMT) on OCT) * No previous oral treatment for CMO for last 3 months * No previous peribulbar or intravitreal treatment for CMO in the study eye for last 3 months * No previous topical treatment for CMO in the study eye for last 1 month * Central visual impairment that in the view of the Principal Investigator is due to CMO * BCVA better than 3/60
Exclusion criteria
* Insufficient patient cooperation or media clarity to allow adequate fundus imaging. * Evidence of visually significant vitreo-retinal traction or epiretinal membrane on OCT that in the Principal Investigator's opinion is highly likely to significantly limit the efficacy of intravitreal therapy. * History of cataract surgery within prior 3 months or cataract surgery anticipated within 6 months of starting the study. * Any anti-VEGF treatment to study eye within 3 months. * History of YAG capsulotomy performed within 3 months. * Uncontrolled Intraocular pressure (IOP) \> = 24 mmHg for ocular hypertension (on topical IOP lowering medications) * Advanced glaucoma (in the opinion of a glaucoma specialist). * Patients with active or suspected ocular or periocular infections * Patients with active severe intraocular inflammation. * Patients with a new, untreated retinal tear or detachment * Patients with a stage 3 or 4 macular hole * Thromboembolic event (MI/CVA/Unstable Angina) within 6 months. * Pregnancy or family planned within 15 months * Females who are breast feeding * Known allergy or hypersensitivity to anti-VEGF products Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 12 weeks after treatment discontinuation. The MHRA advise double contraception. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment. Note: Subjects are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 12 Months | at 12 months | Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Best Corrected Visual Acuity (BCVA) Using the ETDRS Visual Acuity Chart at 6 and 12 Months | baseline to 6 months and baseline to 12 months | Mean Best Corrected Visual Acuity (BCVA) using the ETDRS visual acuity chart at 6 and 12 months. BCVA is the best possible vision an eye can see with corrective lenses, measured using the ETDRS visual acuity chart. The ETDRS score is calculated as the total number of letters correctly read at 4m from the chart plus 30 (if 20 or more letters can be read at 4m). |
| The Mean Change in ETDRS BCVA at 6 Months and at 12 Months | at 6 months and at 12 months | Mean ETDRS BCVA change at 6 months and at 12 months. BCVA is the best possible vision an eye can see with corrective lenses, measured using the ETDRS visual acuity chart. The ETDRS score is calculated as the total number of letters correctly read at 4m from the chart plus 30 (if 20 or more letters can be read at 4m). |
| The Mean Macular Volume on SDOCT at 6 and 12 Months | baseline to 6 months and baseline to 12 months | — |
| The Mean Change in Macular Volume on SDOCT From Baseline to 6 Months and Baseline to 12 Months | baseline to 6 months and baseline to 12 months | — |
| The Mean Change in Central Macular Thickness on Spectral Domain Optical Coherence Tomography (SD-OCT) From Baseline to 6 Months and Baseline to 12 Months | baseline to 6 months and baseline to 12 months | — |
| The Mean Retinal Sensitivity Using Microperimetry at 6 and 12 Months | At 6 months and at 12 months | — |
| The Mean Change in Retinal Sensitivity Using Microperimetry From Baseline to 6 Months and Baseline to 12 Months | From baseline to 6 months and baseline to 12 months | — |
| The Mean Number of Intravitreal Injections Administered | 17 months (from first patient first visit to last patient last visit) | — |
| The Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 6 Months | at 6 months | The Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 6 Months |
| Report All Adverse Events and Serious Adverse Events | From date of first injection for first patient to the end of the study (17 months) | — |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intravitreal Aflibercept for RP-CMO 30 patients recruited for this study, all of which receive the active drug, aflibercept | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Intravitreal Aflibercept for RP-CMO |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United Kingdom | 30 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 26 / 30 |
| serious Total, serious adverse events | 1 / 30 |
Outcome results
Primary
Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 12 Months
Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 12 months
Time frame: at 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 12 Months | 413.4 Microns | Standard Deviation 98.2 |
Secondary
Report All Adverse Events and Serious Adverse Events
Time frame: From date of first injection for first patient to the end of the study (17 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | Report All Adverse Events and Serious Adverse Events | Serious adverse events in whole study | 1 participants |
| Intravitreal Aflibercept for RP-CMO | Report All Adverse Events and Serious Adverse Events | Non-serious adverse events in whole study | 26 participants |
Secondary
The Mean Best Corrected Visual Acuity (BCVA) Using the ETDRS Visual Acuity Chart at 6 and 12 Months
Mean Best Corrected Visual Acuity (BCVA) using the ETDRS visual acuity chart at 6 and 12 months. BCVA is the best possible vision an eye can see with corrective lenses, measured using the ETDRS visual acuity chart. The ETDRS score is calculated as the total number of letters correctly read at 4m from the chart plus 30 (if 20 or more letters can be read at 4m).
Time frame: baseline to 6 months and baseline to 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Best Corrected Visual Acuity (BCVA) Using the ETDRS Visual Acuity Chart at 6 and 12 Months | Mean BCVA at 6 months | 66.9 ETDRS letters | Standard Deviation 10.6 |
| Intravitreal Aflibercept for RP-CMO | The Mean Best Corrected Visual Acuity (BCVA) Using the ETDRS Visual Acuity Chart at 6 and 12 Months | Mean BCVA at 12 months | 68.0 ETDRS letters | Standard Deviation 11.1 |
Secondary
The Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 6 Months
The Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 6 Months
Time frame: at 6 months
Population: 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 6 Months | 414.8 micron | Standard Deviation 96.4 |
Secondary
The Mean Change in Central Macular Thickness on Spectral Domain Optical Coherence Tomography (SD-OCT) From Baseline to 6 Months and Baseline to 12 Months
Time frame: baseline to 6 months and baseline to 12 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Change in Central Macular Thickness on Spectral Domain Optical Coherence Tomography (SD-OCT) From Baseline to 6 Months and Baseline to 12 Months | Mean change in CMT from baseline to 6 months | -46.2 Microns |
| Intravitreal Aflibercept for RP-CMO | The Mean Change in Central Macular Thickness on Spectral Domain Optical Coherence Tomography (SD-OCT) From Baseline to 6 Months and Baseline to 12 Months | Mean change in CMT from baseline to 12 months | -47.6 Microns |
Secondary
The Mean Change in ETDRS BCVA at 6 Months and at 12 Months
Mean ETDRS BCVA change at 6 months and at 12 months. BCVA is the best possible vision an eye can see with corrective lenses, measured using the ETDRS visual acuity chart. The ETDRS score is calculated as the total number of letters correctly read at 4m from the chart plus 30 (if 20 or more letters can be read at 4m).
Time frame: at 6 months and at 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Change in ETDRS BCVA at 6 Months and at 12 Months | Mean change in BCVA from baseline to 6 months | 3.1 ETDRS letters | Standard Deviation 6.6 |
| Intravitreal Aflibercept for RP-CMO | The Mean Change in ETDRS BCVA at 6 Months and at 12 Months | Mean change in BCVA from baseline to 12 months | 4.3 ETDRS letters | Standard Deviation 6.9 |
Secondary
The Mean Change in Macular Volume on SDOCT From Baseline to 6 Months and Baseline to 12 Months
Time frame: baseline to 6 months and baseline to 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Change in Macular Volume on SDOCT From Baseline to 6 Months and Baseline to 12 Months | Mean change mac volume from baseline to 6 months | -0.3 millimeters cubed | Standard Deviation 0.8 |
| Intravitreal Aflibercept for RP-CMO | The Mean Change in Macular Volume on SDOCT From Baseline to 6 Months and Baseline to 12 Months | Mean change mac volume from baseline to 12 months | -0.3 millimeters cubed | Standard Deviation 0.7 |
Secondary
The Mean Change in Retinal Sensitivity Using Microperimetry From Baseline to 6 Months and Baseline to 12 Months
Time frame: From baseline to 6 months and baseline to 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Change in Retinal Sensitivity Using Microperimetry From Baseline to 6 Months and Baseline to 12 Months | Mean change ret sens from baseline to 6 months | -1.23 decibels | Standard Deviation 2.24 |
| Intravitreal Aflibercept for RP-CMO | The Mean Change in Retinal Sensitivity Using Microperimetry From Baseline to 6 Months and Baseline to 12 Months | Mean change ret sens from baseline to 12 months | -1.09 decibels | Standard Deviation 2.1 |
Secondary
The Mean Macular Volume on SDOCT at 6 and 12 Months
Time frame: baseline to 6 months and baseline to 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Macular Volume on SDOCT at 6 and 12 Months | Mean macular volume at 6 months | 7.9 millimeters cubed | Standard Deviation 0.6 |
| Intravitreal Aflibercept for RP-CMO | The Mean Macular Volume on SDOCT at 6 and 12 Months | Mean macular volume at 12 months | 8.0 millimeters cubed | Standard Deviation 0.7 |
Secondary
The Mean Number of Intravitreal Injections Administered
Time frame: 17 months (from first patient first visit to last patient last visit)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Number of Intravitreal Injections Administered | 7 injections |
Secondary
The Mean Retinal Sensitivity Using Microperimetry at 6 and 12 Months
Time frame: At 6 months and at 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intravitreal Aflibercept for RP-CMO | The Mean Retinal Sensitivity Using Microperimetry at 6 and 12 Months | Mean retinal sensitivity at 6 months | 4.92 decibels | Standard Deviation 3.49 |
| Intravitreal Aflibercept for RP-CMO | The Mean Retinal Sensitivity Using Microperimetry at 6 and 12 Months | Mean retinal sensitivity at 12 months | 4.93 decibels | Standard Deviation 3.49 |