Clinical trial NCT02661711: Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
Official title: Prospective Non-randomised Exploratory Study to Assess the Safety and Efficacy of Aflibercept (Eylea) in Cystoid Macular Oedema (CMO) Associated With Retinitis Pigmentosa (RP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Macular Oedema
Retinitis Pigmentosa
Keywords: Macular Oedema Retinitis Pigmentosa
Lead sponsor: Moorfields Eye Hospital NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2016-01-22
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 12 Months
timeFrame: at 12 months
Secondary outcomes:
measure: 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
timeFrame: baseline to 6 months and baseline to 12 months
measure: The Mean Best Corrected Visual Acuity (BCVA) Using the ETDRS Visual Acuity Chart at 6 and 12 Months
timeFrame: baseline to 6 months and baseline to 12 months
measure: The Mean Change in ETDRS BCVA at 6 Months and at 12 Months
timeFrame: at 6 months and at 12 months
measure: The Mean Macular Volume on SDOCT at 6 and 12 Months
timeFrame: baseline to 6 months and baseline to 12 months
measure: The Mean Change in Macular Volume on SDOCT From Baseline to 6 Months and Baseline to 12 Months
timeFrame: baseline to 6 months and baseline to 12 months
measure: Report All Adverse Events and Serious Adverse Events
timeFrame: From date of first injection for first patient to the end of the study (17 months)
measure: The Mean Retinal Sensitivity Using Microperimetry at 6 and 12 Months
timeFrame: At 6 months and at 12 months
measure: The Mean Change in Retinal Sensitivity Using Microperimetry From Baseline to 6 Months and Baseline to 12 Months
timeFrame: From baseline to 6 months and baseline to 12 months
measure: The Mean Number of Intravitreal Injections Administered
timeFrame: 17 months (from first patient first visit to last patient last visit)
measure: The Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 6 Months
timeFrame: at 6 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
Study officials:
affiliation: Moorfields Eye Hospital, Institute of Ophthalmology
name: Michel Michaelides, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Strong SA, Peto T, Bunce C, Xing W, Georgiou M, Esposti SD, Kalitzeos A, Webster A, Michaelides M. Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa. Br J Ophthalmol. 2020 Sep;104(9):1203-1208. doi: 10.1136/bjophthalmol-2019-315152. Epub 2020 Feb 10.