Inherited Retinal Diseases research at Moorfields

Transcription

1 Recruiting Research Studies Inherited Retinal Diseases research at Moorfields Moorfields Eye Hospital wants to improve access to clinical research studies for all patients within the NHS and provide the opportunities for patients to participate in research. This is a list of research studies that are currently open and recruiting patients at Moorfields Eye Hospital. This includes information about the study, the lead consultant on the study, and the currently anticipated date that patient recruitment will end. If no end date is stated, then the study has no set end date and will continue to recruit patients for the foreseeable future. If you are interested in any of the listed studies, we advise that you approach your Moorfields consultant for more information. If you are not a Moorfields patient, you will need to be referred to Moorfields Eye Hospital by your NHS GP to be able to participate in any of these studies. For further information, please res-admin@moorfields.nhs.uk If a member of our staff thinks you might meet the specific criteria for a study, they will discuss it with you in detail. You might be approached during your visit to the hospital, or receive a letter or phone call after your visit. You will be given time to consider whether you would like to take part and what the implications will be for you. All clinical research projects are strictly monitored by our research department and regulated by national bodies. You will need to give explicit written consent if you decide you would like to take part. Version: 1 Page 1 of 10 Status: PUBLISHED Approved: 25 th May 2018 Ratified: 25 th May 2018

2 BAIJ1012 Gene therapy trial for LCA An open-label, multi-centre, Phase I/II dose escaltion trial of an adeno-associated virus vector (AAV2/5-OPTIRPE65) for gene therapy of adults and children with retinal dystrophy associated with defects in RPE65 (LCA2) Consultant: Prof James Bainbridge Recruitment End Date: 01/04/2018 BAIJ1014 An open label, multi-centre, Phase I/II dose escalation trial of a recombinant adeno-associated virus vector (raav2/8- hcarp.hcngb3) for gene therapy of adults and children with achromatopsia owing to defects in CNGB3 Achromatopsia is a recessively inherited condition characterised by a lack of cone photoreceptor function resulting in impairment of colour vision and visual acuity, central scotoma often with eccentric fixation, disabling hypersensivity to light(photophobia) and involuntary eye movements (pendular nystagmus). Children with CNGB3-related achromatopsia have profound sight impairment from birth or early infancy. The condition is currently untreatable, but there is a real possibility that a gene therapy could offer a significant benefit in terms of improved sight and quality of life (QOL), based on our own and others experience of ocular gene therapy trials (Maguire, et al 2008; Cideciyan, AV et al 2008 and 2013; Bainbridge, et al 2015) and pre-clinical data demonstrating improved outcome in CNGB3- related achromatopsia. Possible benefits of improved cone-photoreceptor function include improved visual acuity; improved colour perception; and relief from disabling photophobia. Although younger individuals may benefit most from gene supplementation therapy by virtue of their greater visual plasticity, we anticipate that the intervention may offer benefit across a range of ages and we aim to define this range. For this reason, participants of various ages will be included; children will be included only after an acceptable safety profile has been established in adults. Consultant: Prof James Bainbridge Recruitment End Date: 20/08/2018 Inherited Retinal Diseases Research at Moorfields Page 2 of 10

3 BAIJ1015 An open label, multi-centre, Phase I/II dose escalation trial of a recombinant adeno-associated virus vector (AAV2/5-hRKp.RPGR) for gene therapy of adults and children with X-linked Retinitis Pigmentosa owing to defects in Retinitis Pigmentosa GTPase Regulator (RPGR) X-linked retinitis pigmentosa (XLRP) is the name given to a group of inherited eye diseases that affect the retina (the light-sensitive part of the eye). Changes in the RPGR genes account for most cases of X-linked retinitis pigmentosa which is more common in men. RP causes the breakdown of photoreceptor cells (cells in the retina that detect light). Photoreceptor cells capture and process light helping us to see and as these cells breakdown and die, patients experience progressive vision loss. The first sign of retinitis pigmentosa is usually night blindness which becomes apparent in childhood or early adulthood and is progressive throughout the subject s life-time. There is currently no treatment for RP. Gene therapy is considered the most promising treatment among a variety of novel therapeutic strategies that are currently under investigation. In patients with RP associated with mutations in the RPGR gene, a functional gene replacement may facilitate the functional and morphological rescue of the photoreceptor cells and consequently improved vision. We will include affected people of various ages in this study and children will be included once safety has been established in adults. Consultant: Prof Jim Bainbridge Recruitment End Date: 03/04/2020 Inherited Retinal Diseases Research at Moorfields Page 3 of 10

4 BAIJ1016 Long-term follow-up study of participants following an open label, multi-centre, Phase I/II dose escalation trial of a recombinant adeno-associated virus vector (AAV2/8- hcarp.hcngb3) for gene therapy of adults and children with achromatopsia owing to defects in CNGB3 Study Description (IRAS Form?) The follow up study is designed to collect data on longer-term safety and efficacy at 9, 12, 24, 36, 48 and 60 month timepoints following AAV2/8-hCARp.hCNGB3 administration in the CNGB3 trial. The Achromatopsia CNGB3 trial is an on-going open-label, Phase I/II doseescalation study to determine the safety and efficacy of a subretinal administration of the ATIMP in participants with achromatopsia. In the dose escalation phase, up to 18 adult participants are administered one of 3 different doses of vector in cohorts of 3 participants at a time, using a 3+3 design. Based on toxicity data, the IDMC makes a recommendation on the dose to administer to the next cohort of 3 participants. The IDMC may recommend additional participant are administered any dose before making another decision. Up to 9 children or adults will be included once an acceptable safety profile has been established in adults. The IDMC will agree the maximum tolerated dose in adults before recommending administration of this dose to children. Safety and efficacy is being assessed by clinical examination and special investigations according to a pre-defined schedule of follow up visits, for 6 months following the intervention. At the 3 month follow up visit of the CNGB3 trial (3 months post-administration), participants will be invited to join this longer-term follow-up study, in which they will be assessed for safety for up to 60 months following AAV2/8- hcarp.hcngb3 administration. Consultant: Prof Jim Bainbridge Recruitment End Date: 20/03/2020 MICM1002 An Exploratory Clinical and Molecular Genetic Study of Stationary and Progressive Disorders of Cone Function This research study aims to investigate these conditions in detail to help improve our understanding of the causes of visual impairment in these conditions; to investigate to what degree change occurs over time and to identify the genetic causes of these disorders. This information will assist in the provision of better information for patients and may also be helpful in the event of future anticipated treatment trials. The research aims to improve our understanding of these disorders in order to provide better information to patients and also to shed light on the causes of visual loss in these conditions. We want to establish the genetic cause of these disorders. Consultant: Prof Michel Michaelides Recruitment End Date: 18/06/2019 Inherited Retinal Diseases Research at Moorfields Page 4 of 10

5 MICM1003 Phenotyping Patients with Leber Congenital Amaurosis Associated with Mutations in AIPL1 in Preparation for Gene Therapy Trials This research study aims to provide detailed information about retinal function and how this changes over time in patients with AIPL1 gene defects. We hope that this will lead to a better understanding of the condition and assist in providing improved information to patients and also assist in developing future treatment strategies. We want to improve our understanding of the retinal function and structure, and how this changes over time, in patients with AIPL1 gene defects and to be able to provide improved information to patients and also assist in developing future treatment strategies Consultant: Prof Michel Michaelides Recruitment End Date: 19/01/2019 MICM1004 A Study of Conditions Affecting the Retina The retina is the light sensitive layer at the back of the eye. The eye has many similarities to a camera. The retina is similar to the film in a camera. There are many problems affecting the retina that mainly affect the light sensitive cells called rods and cones, especially in the early stages. Rod cells are mainly used for night-time vision and cone cells are mainly used for day-time vision and reading. We are trying to learn more about the causes of these conditions and look at how well the rod and cone cells work and whether this changes in different people as they get older. Consultant: Prof Michel Michaelides Recruitment End Date: 30/05/2019 MICM1006 Magnetic Resonance Imaging Studies for Children with Achromatopsia The study is being carried out to investigate the relationship between visual cortex structure and function using structural and functional MRI, correlate phenotypic findings with genotype and explore the use of determining efficacy of planned gene replacement therapy using structural and functional MRI and probe the potential role that variable cerebral plasticity may have on limiting treatment effects. The preliminary investigations will aim to determine whether the previously reported cerebral reorganisation that can occur in achromatopsia is age- or genotype- dependent. Consultant: Prof Michel Michaelides Recruitment End Date: 31/03/2019 Inherited Retinal Diseases Research at Moorfields Page 5 of 10

6 MICM1011 Advanced Ocular Imaging Program Bank Researchers at the Medical College of Wisconsin, in collaboration with others, have created a bank called The Advanced Ocular Imaging Program Bank" that seeks to collect ocular images, eye-related health information, and genetic results from a large number of people with different eye conditions. This information will then be banked so that in the future, other doctors and scientists at medical and research centres around the world may use it to learn about many different diseases and conditions. Their goal is to improve health and develop new treatments. Consultant: Prof Michel Michaelides Recruitment End Date: 01/12/2018 MICM1017 RPE65 Natural History Study Natural History of patients with Leber Congenital Amaurosis associated with mutations in RPE65 Consultant: Prof Michel Michaelides Recruitment End Date: 30/06/2018 MOOM1003 Priorities and Preferences for Whole Genome Sequencing Whole genome sequencing is set to become the gold standard in diagnostic genetic testing and is already being used in certain circumstances. The arrival the 100,000 Genomes Project is set to increase the number of patients referred for whole genome sequencing dramatically. The primary goal of this study is to evaluate whether patients who are being offered Whole genome sequencing are making an informed decision to accept or decline testing Consultant: Mariya Moosajee Inherited Retinal Diseases Research at Moorfields Page 6 of 10

7 MOOA1017 Assessment of the impact of different eye diseases on sleep, sleep/wake timing and circadian entrainment with genotyping Our sleep/wake cycles are controlled by a receptor situated at the back of the eye. These receptors are sensitive to blue light and are known as the photosensitive retinal ganglion cells (prgc). Depending on whether it is day or night, different amounts of light pass into the eye. As light enters the eye, this receptor detects how much blue light is present, and sends a signal to a certain part of the brain. This part of the brain controls the sleep/wake cycle that ensures a person sleeps at night and is awake during the day. The light input can be upset for a number of reasons. For example, certain eye conditions like glaucoma, inherited retinal degenerations or macular degeneration may cause reduced light perception due to the changes at the back of the eye where the prgc system is situated. This in turn may have an impact on sleep/wake cycle. Indeed a significant proportion of patients with progressive degenerative eye disease such as inherited retinal degeneration, glaucoma or with other visual impairment have been shown to suffer from sleep disturbances. A common condition where the lens gets cloudy and stops as much light entering the eye is cataract. As well as affecting the vision, cataract also reduces the amount of the blue light transmission reaching the back of the eye and thereby may affect sleep. Removal of cataract has shown to improve the sleep patterns in some patients in the preliminary results of one of our ongoing study. By assessing the impact of different eye conditions on sleep patterns and sleep/wake cycle we plan to develop an informed approach in the overall management of the various eye problems. Consultant: Mr Andrew Webster Recruitment End Date: 31/12/2018 MOOA1019 MRI tractography study The aim of this project is fourfold: (1) To investigate the anatomy of the visual system in healthy children and to determine the volume of the visual pathways and measures of the structural integrity within the pathway. (2) To determine quantitative measures of the structural integrity of the visual pathways in children with abnormalities of the visual system. (3) To compare and correlate functional measures, namely electrophysiology and functional imaging of normal and abnormal visual pathway conduction with tractography. (4) To appraise and develop tractography as a complementary tool to existing investigative procedures in children with visual system abnormalities and to determine its future clinical role in visual system investigations. Consultant: Mr Robert Henderson Inherited Retinal Diseases Research at Moorfields Page 7 of 10

8 WEBA1014 REGENERATE (REP1 Gene Replacement Therapy) An open label Phase 2 clinical trial of retinal gene therapy for choroideremia using an adeno-associated viral vector (AAV2) encoding Rab-escort protein 1 (REP1) Consultant: Mr Andrew Webste WEBA1018 RP Genome Project This is a genetic study involving collection of samples of blood, saliva or tissue for DNA extraction and Next Generation Sequencing (NGS) of exome or whole genome. DNA samples will be retained for future use, and induced pluripotent stem cells may be created (both with prior consent). Incidental findings unrelated to Inherited Retinal Dystrophy (IRD) that are of clinical significance will be validated and reported to participants clinical care teams Consultant: Prof Andrew Webster YUWP1001 Genotype and Phenotype in Inherited Neurodegenerative Disease Changes in research are allowing scientists to design new therapeutic options for many genetic diseases. Current and future research might help us to understand genetic diseases even better and therefore improve the ability to develop treatments for people suffering from rare diseases. Consultant: Mr Patrick Yu Wai Man Recruitment End Date: 30/09/2018 Inherited Retinal Diseases Research at Moorfields Page 8 of 10

9 YUWP1006 EURO-WABB: An EU Rare Diseases Registry for Wolfram Syndrome, Alstrom Syndrome, Bardet-Biedl Syndrome and Other Rare Diabetes Syndromes Wolfram, Alström and Bardet Biedl (BBS) (WABB) syndromes are rare genetic diseases with clinical overlap, chronically debilitating, and highly complex. Patients are distributed throughout the EU. The diseases progress to death in early adulthood. EUROWABB is an international registry of children and adults WABB and other rarer diabetes syndromes, containing anonymised clinical data on history and examination, complications, laboratory investigations, imaging; and molecular genetic data; and information on human tissue held locally. The purpose of the webbased registry is: a) to establish the natural history of these diseases (their characteristics, management and outcomes); b) to assess clinical effectiveness of management and quality of care; c) to provide a register of patients for recruitment to intervention studies; d) to establish genotypephenotype correlations. Data held in the registry will be anonymised (there will be no personal identifiable data held); but linked by a unique identifier to the health professional who submitted the data. The local health professional can submit data records on his/her patients, and controls access to data records for patients under their care. Patients will be able to submit some of their own personal data if they want. The detailed clinical characterisation will allow future enrolment into multinational clinical trials (with separate consent). The registry will support wider access to genetic testing, information for affected families and health professionals; and encourage international collaborations for patient benefit. Research partners can register and apply to the EUROWABB scientific committee with research proposals to access the registry data. Proposals will need to have the relevant national ethics approvals. If direct access to patients to participate in research studies is required, this will only be through their local health professionals. Additionally, the Wolfram SubStudy of EuroWABB to collect longitudinal natural history data from a selection of Wolfram Syndrome participants that are already participating in the EuroWABB registry. Consultant: Mr Patrick Yu Wai Man Recruitment End Date: 31/03/2018 YUWP1007 External natural history controlled, open-label intervention study to assess the efficacy and safety of long-term treatment with Raxone in Leber s hereditary optic neuropathy (LHON) - LEROS This is a Phase 4 clinical research study, called LEROS. The LEROS study is aiming to find out more about the effectiveness and safety of the study drug (Raxone) in the long-term treatment of Leber s hereditary optic neuropathy (LHON). The study drug has already been approved in the European Union for the treatment of LHON. Approximately 250 patients at 25 study centres across several European countries will take part in this study. Consultant: Mr Patrick Yu Wai Man Inherited Retinal Diseases Research at Moorfields Page 9 of 10

10 YUWP1012 Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials. This is a Phase III prospective non-interventional (No IMP administered) long-term follow-up clinical study of participants previously enrolled in two Phase III studies RESCUE and REVERSE. Leber hereditary optic neuropathy (LHON) is an inherited form of blindness caused by pathogenic mutations (spelling mistakes) within the genetic code contained within mitochondria. Mitochondria are the powerhouses within cells and produce most of the energy required for normal cellular function. The majority of patients with LHON carry a specific mutation within the mitochondrial ND4 gene (denoted as G11778A) where due to a mutation the genetic code it now instructs formation of a ND4 protein with a compromised function. During the RESCUE and REVERESE studies participants were administered a single injection with a gene therapy named GS010, aimed at delivering a functional ND4 protein to the deficient mitochondria. This study will monitor these participants over an additional 3 years after the RESCUE and REVERSE studies end. Consultant: Mr Patrick Yu Wai Man Inherited Retinal Diseases Research at Moorfields Page 10 of 10