Safety and Efficacy of the Alpha AMS Subretinal Implant (OX-RI)

Safety and Efficacy of the Alpha AMS Subretinal Implant for Partial Restoration of Vision in Visually Impaired Participants With Degenerative Retinal Disease

The aim of this single-centre study is to assess the safety and efficacy of the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) in participants with severe visual impairment secondary to outer retinal degeneration caused by retinitis pigmentosa (RP). The study is sponsored by the University of Oxford and funded by the National Institute for Health Research (UK).

Study Overview

• Status: Completed
• Conditions: Retinitis Pigmentosa
• Intervention / Treatment: Device: Implant 'on' vs implant 'off'

Detailed Description

The specific research questions are, i) can the implant partially restore vision to an eye with no light perception and ii) what are the safety implications for the ocular and periorbital tissues of the implanted eye? In advanced RP the light detecting photoreceptor cells of the retina degenerate slowly over time, and may eventually lead to blindness. The subretinal implant replaces the degenerate photoreceptor layer and stimulates the residual overlying healthy retinal layers in response to a light stimulus. These signals are then carried on to the brain along the normal visual pathway. Investigators are seeking to recruit six participants who fulfill the eligibility criteria, which include advanced RP with no useful light perception vision in the eye to receive the implant. Participants must be aged between 18 and 70 years old, be highly motivated, and be well enough for a general anaesthetic. The eye must have also had cataract surgery. The project will be conducted at the Oxford Eye Hospital. Those participants selected to receive the implant will be followed for 12 months from the date of surgery. Between week 1 and month 12 there will be at least 7 outpatient clinic visits for a range of visual tests and eye assessments. After 12 months the trial will officially end, however investigators will continue to review all research participants in clinic as would be standard care for a patient with RP. The implant may be removed at any stage e.g. when it ceases to function or at the participant's request.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Oxford University Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the trial.
• Male or Female, aged 18 to 70 years old.
• Hereditary retinal degeneration of the outer retinal layers i.e. photoreceptor rods & cones.
• Angiography shows retinal vessels adequately perfused, despite pathological RP condition.
• Severe visual impairment (at least monocular) i.e. visual functions insufficient for localization of objects, self-sustained navigation and orientation e.g. impaired light localization or worse.
• Ability to read normal print in earlier life, optically corrected (without magnifying glass).
• Able to participate in the study during the full time period of one year.
• Pseudophakic in the eye to receive the implant.
• Stable dose of current regular medication for at least four weeks prior to trial entry.
• Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial.
• Participant has clinically acceptable laboratory and ECG results as confirmed at - Screening Visit and upon review by consultant anaesthetist.
• In the Investigator's opinion, is able and willing to comply with all trial requirements.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

Exclusion Criteria:

• Period of appropriate visual functions < 12 years / lifetime.
• Optical coherence tomography (OCT) shows significant retina oedema &/or scar tissue within target region for implant.
• Retina detected as too thin to expect required functionality of inner retina as shown via OCT.
• Lack of inner-retinal function, as determined by Electrically Evoked Phosphenes (EEP).
• Heavy clumped pigmentation at posterior pole.
• Any other ophthalmologic disease with relevant effect upon visual function (e.g. glaucoma, optic neuropathies, trauma, diabetic retinopathy, retinal detachment).
• Amblyopia reported earlier in life for eye to be implanted.
• Systemic diseases that might imply considerable risks with regard to the surgical interventions and anesthesia (e.g. cardiovascular/ pulmonary diseases, significant metabolic diseases e.g. diabetes).
• Neurological and/or psychiatric diseases (e.g. Parkinson, epilepsy, depression).
• Hyperthyroidism or hypersensitivity to iodine.
• Hypersensitivity to fluorescent dye (fluorescence angiography).
• Women who are pregnant or nursing, or women of childbearing age who are not willing to use a medically acceptable means of birth control for the duration of the study, or women unwilling to perform a pregnancy test before entering the study.
• Participation in another interventional clinical trial within the past 12 weeks.
• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Implant 'on' vs implant 'off'; Intra-individual comparison of implant 'on' vs implant 'off'	Device: Implant 'on' vs implant 'off'; Single group assignment; Other Names: Alpha AMS; Retinal Implant Alpha AMS; Retinal implant; Bionic eye; Retinal prosthesis; Sub retinal chip

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of the Alpha AMS retinal implant system used for activities of daily living tasks.	Activities of daily living are assessed with implant ON versus OFF via: • Activities of daily living tasks	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of the Alpha AMS retinal implant system used for partial restoration of visual acuity.	Visual acuity or light-perception and/or object-recognition assessed with implant ON versus OFF via • Freiburg visual Acuity and Contrast Test (FrACT)	12 months
Efficacy of the Alpha AMS retinal implant system used for partial restoration of basic light detection..	Visual acuity or light-perception and/or object-recognition assessed with implant ON versus OFF via: • Basic Light and Motion test (BaLM)	12 months
Efficacy of the Alpha AMS retinal implant system used for partial restoration of grating acuity.	Visual acuity or light-perception and/or object-recognition assessed with implant ON versus OFF via: • Basic Grating Acuity test (BaGA).	12 months
Safety of the Alpha AMS retinal implant.	The number of participant with Adverse Events and/or Serious Adverse Events, as defined by the Study Protocol, will be reported.	12 months

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: Robert E MacLaren, DPhil FRCS, 1. Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford; 2. Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust; 3. Moorfields Eye Hospital NHS Foundation Trust, London

Publications and helpful links

General Publications

• Cehajic Kapetanovic J, Troelenberg N, Edwards TL, Xue K, Ramsden JD, Stett A, Zrenner E, MacLaren RE. Highest reported visual acuity after electronic retinal implantation. Acta Ophthalmol. 2020 Nov;98(7):736-740. doi: 10.1111/aos.14443. Epub 2020 Apr 28.
• Stingl K, Schippert R, Bartz-Schmidt KU, Besch D, Cottriall CL, Edwards TL, Gekeler F, Greppmaier U, Kiel K, Koitschev A, Kuhlewein L, MacLaren RE, Ramsden JD, Roider J, Rothermel A, Sachs H, Schroder GS, Tode J, Troelenberg N, Zrenner E. Interim Results of a Multicenter Trial with the New Electronic Subretinal Implant Alpha AMS in 15 Patients Blind from Inherited Retinal Degenerations. Front Neurosci. 2017 Aug 23;11:445. doi: 10.3389/fnins.2017.00445. eCollection 2017.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (ACTUAL): October 1, 2017
• Study Completion (ACTUAL): October 1, 2017

Study Registration Dates

• First Submitted: December 4, 2015
• First Submitted That Met QC Criteria: March 21, 2016
• First Posted (ESTIMATE): March 28, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Retinitis; Retinitis Pigmentosa
• Other Study ID Numbers: E/2015/0119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED