Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study

Phase 2

Completed

Conditions: Macular Oedema
Retinitis Pigmentosa

Interventions: Drug: Aflibercept

Registration Number: NCT02661711

Lead Sponsor: Moorfields Eye Hospital NHS Foundation Trust

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Aflibercept (Eylea)	Aflibercept	All patients recruited to the study will receive 3 loading intravitreal injections of Aflibercept (Eylea) at monthly intervals 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 when there is evidence of OCT stability in the view of the investigator i.e. there is no further reduction in macular fluid compared to the previous visit. All patients will receive 5 injections before considering them non-responders.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Report All Adverse Events and Serious Adverse Events	From date of first injection for first patient to the end of the study (17 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 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 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 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
The Mean Macular Volume on SDOCT at 6 and 12 Months	baseline to 6 months and baseline to 12 months