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

• ClinicalTrials.gov Identifier: NCT02661711
• Recruitment Status: Unknown
• First Posted: January 22, 2016
• Last Update Posted: September 14, 2016
• Sponsor: Moorfields Eye Hospital NHS Foundation Trust
• Collaborator: Bayer
• Information provided by (Responsible Party): Moorfields Eye Hospital NHS Foundation Trust

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Macular Oedema; Retinitis Pigmentosa	Drug: Aflibercept	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: March 2016
• Estimated Primary Completion Date: October 2017
• Estimated Study Completion Date: October 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: Aflibercept (Eylea); 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.

Drug: Aflibercept; 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.; Other Name: Eylea

Outcome Measures

Primary Outcome Measures :

1. The efficacy of Eylea in cystoid macular oedema (CMO) associated with Retinitis Pigmentosa (RP) [ Time Frame: baseline to 12 months ]
   Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) at 12 months will assess the efficacy of the study; the number of Participants With Abnormal mean central macular thickness values.
2. The safety of Eylea in cystoid macular oedema (CMO) associated with Retinitis Pigmentosa (RP) [ Time Frame: baseline to 12 months ]
   Safety will be assessed by the Adverse Events that are related to treatment and Mean Central Macular Thickness (CMT) on Spectral Domain OCT (SDOCT) to assess if Eylea has reduced fluid accumulation in the retina.

Secondary Outcome Measures :

1. The mean central macular thickness (CMT) on Spectral Domain OCT (SDOCT) at 6 months [ Time Frame: Baseline to 6 months ]
2. 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 ]
3. The mean Best Corrected Visual Acuity (BCVA) using the ETDRS visual acuity chart at 6 and 12 months [ Time Frame: baseline to 6 months and baseline to 12 months ]
4. The mean change in ETDRS BCVA from baseline to 6 months and baseline to 12 months [ Time Frame: baseline to 6 months and baseline to 12 months ]
5. The mean macular volume on SDOCT at 6 and 12 months [ Time Frame: baseline to 6 months and baseline to 12 months ]
6. 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 ]
7. 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) ]
8. The mean retinal sensitivity using microperimetry at 6 and 12 months [ Time Frame: At 6 months and at 12 months ]
9. 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 ]
10. The mean number of intravitreal injections administered [ Time Frame: 17 months (from first patient first visit to last patient last visit) ]

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United Kingdom

Moorfields Eye Hospital

London, United Kingdom, EC1V 2PD

Sponsors and Collaborators

Moorfields Eye Hospital NHS Foundation Trust

Bayer

Investigators

• Principal Investigator: Michel Michaelides, Professor; Moorfields Eye Hospital, Institute of Ophthalmology

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Moorfields Eye Hospital NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT02661711
• Other Study ID Numbers: MICM1014; 2015-003723-65 ( EudraCT Number )
• First Posted: January 22, 2016
• Last Update Posted: September 14, 2016
• Last Verified: September 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Individual patient data will not be disclosed publically, all the data will be anonymised and analysed in accordance with the Data Protection Act

Keywords provided by Moorfields Eye Hospital NHS Foundation Trust:

Macular Oedema Retinitis Pigmentosa

Additional relevant MeSH terms:

Macular Edema; Retinitis; Retinitis Pigmentosa; Edema; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Genetic Diseases, Inborn; Aflibercept; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents