A phase II clinical trial of Detection of Apoptosing Retinal Cells (DARC II)
| ISRCTN | ISRCTN10751859 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10751859 |
| EudraCT/CTIS number | 2016-002531-15 |
| Secondary identifying numbers | 31894 |
- Submission date
- 03/04/2017
- Registration date
- 03/04/2017
- Last edited
- 22/05/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Plain English summary of protocol
Background and study aims
The retina is the name given to the layer at the back of the eye which is sensitive to light. When light enters the eye, the cells that make up the retina convert the light rays into electrical impulses, which travel via the optic nerve into the brain so they can be interpreted as images. Apoptosis is a process of programmed cell death or “cellular suicide”. DARC Technology (Detection of Apoptosing Retinal Cells) is a new technique that uses the unique properties of the eye to make it possible to view nerve cells in the eye dying via optosis. The technique uses a substance called ANX776, which has previously been shown to be well tolerated in patients and cause minimal side effects. The aim of this study is to further evaluate the extent to which it is possible to see apoptosis in retinal cells in patients with a range of long-term eye diseases and healthy people of the same age.
Who can participate?
Adults with eye diseases and healthy volunteers of the same age.
What does the study involve?
All participants attend a single study visit at which they receive an injection of ANX776 into a vein. Following this, they undergo an eye exam in order to look at the retina. Participants are followed up with a telephone call after 30 days to find out if they have had any side effects.
What are the possible benefits and risks of participating?
There are unlikely to be any direct benefits involved with participating, although the information gained from this study may help to improve treatment for future patients. The main risks are discomfort during the eye examination, or discomfort caused by bright, flashing lights. One of the tests is an intra-ocular pressure measurement (which measures the pressure inside the eye). There is a very small chance of getting a scratch on the surface of the eye during this test. If this does happen, it should heal on its own. The trial involves eye numbing drops which in rare cases may cause an allergic reaction, difficulty in breathing or low blood pressure. The study drug will be injected using a cannula. Risks and side effects are bruising, swelling, infection, or bleeding.
Where is the study run from?
Western Eye Hospital (UK)
When is the study starting and how long is it expected to run for?
February 2017 to August 2018
Who is funding the study?
Wellcome Trust (UK)
Who is the main contact?
Ms Francesca Cordeiro
m.cordeiro@ucl.ac.uk
Contact information
Public
Western Eye Hospital
171 Marylebone Road
London
NW1 5QH
United Kingdom
| Phone | +44 20 3312 3206 |
|---|---|
| m.cordeiro@ucl.ac.uk |
Study information
| Study design | Non-randomised; Interventional; Design type: Diagnosis, Drug, Imaging |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A phase II, open label, non-randomised, single centre, clinical trial of ANX776 in healthy volunteers and patients with Glaucoma, Age-Related Macular Degeneration, Optic Neuritis and Down’s Syndrome |
| Study acronym | DARC II |
| Study objectives | Current study hypothesis as of 21/06/2017: The aim of this study is to evaluate the efficacy of DARC in visualising apoptotic retinal cells in patients with glaucoma, age-related macular degeneration, optic neuritis, Down’s syndrome and in healthy volunteers Previous study hypothesis: The aim of this study is to evaluate the efficacy of DARC in visualising apoptotic retinal cells in patients with glaucoma, age-related macular degeneration, optic neuritis, and in healthy volunteers. |
| Ethics approval(s) | London – Harrow REC, 20/12/2016, ref: 16/LO/1700 |
| Health condition(s) or problem(s) studied | Specialty: Ophthalmology, Primary sub-specialty: Retina (including Diabetes); UKCRC code/ Disease: Eye/ Other disorders of eye and adnexa |
| Intervention | The intervention involves as a single injection of the study drug (0.4mg of ANX776). The injection will be given through a cannula that will be placed in a vein in the participants arm. The injection will only last a few seconds, and the cannula will be removed immediately after the injection. Images of the participants retina will be taken using a computer imaging system called scanning laser ophthalmoscopy. All participants will be followed up for adverse events for 30 days by receiving a telephone call 30 days after the injection to check if they have experienced any side effects. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | ANX776 |
| Primary outcome measure | Efficacy of the intervention ascertained by the DARC Count, which is the number of apoptosing retinal cells visualised 4 hours after the ANX776 injection. |
| Secondary outcome measures | Safety, defined as absence of adverse events of grade 3 or above and measured by the Common Terminology Criteria for Adverse Events (CTCAE) scale in clinic after the injection, and by telephone 30 days after the injection. |
| Overall study start date | 01/07/2016 |
| Completion date | 31/08/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 120; UK Sample Size: 120 |
| Total final enrolment | 113 |
| Key inclusion criteria | Current inclusion criteria as of 21/06/2017: General Inclusion Criteria are: 1. Age ≥ 18 years 2. Clear optical media in the studied eye 3. Refractive error not higher than spherical equivalent of 10 D 4. Women of childbearing potential identified as not pregnant and have agreed to complete a pregnancy test Group Specific Inclusion criteria are: Glaucoma: 1. Subjects will show progression in one or more of the parameters measured and will have at least one eye with a diagnosis of glaucoma (abnormal optic disc and/or visual field defect or both); be diagnosed as a glaucoma suspect or ocular hypertensive (elevated IOP). 2. Subjects proven to be able to perform reliable visual field testing using the HFA 640, central 24-2 program, to yield full thresholds, and have had good fundoscopy with assessment of their optic disc. Age-related Macular Degeneration: 1. Patients with AMD as defined by: 2. Early AMD mainly characterised by drusen, retinal pigment epithelium (RPE) pigment changes. 3. Late AMD mainly characterised as: geographic atrophy of the RPE (dry AMD). 4. Neovascular AMD (wet AMD). Optic Neuritis: 1. Clinical diagnosis of optic neuritis affecting one eye within two years 2. Visual acuity in affected eye ≤ 6/12 at worst point 3. Corrected vision in unaffected eye ≥ 6/6 4. No history of optic neuritis or other ocular disease in either eye prior to the episode of optic neuritis 5. Subjects proven to be able to perform reliable visual field testing using the HFA 640, central 24-2 program, to yield full thresholds, and have had good fundoscopy with assessment of their optic disc Down’s Syndrome: 1. Confirmation of Down’s syndrome diagnosis as provided by parent of GP 2. Capacity to provide assent 3. Previously participated in an invasive research trial with the Cambridge Intellectual and Developmental Disabilities Research Group (CIDDRG) 4. No clinical diagnosis of dementia or other psychiatric illness 5. No evidence of serious cognitive decline or onset of dementia from historical records Healthy Volunteers: 1. Confirmation of medical history as confirmed by General Practitioner 2. No evidence of any eye disease Previous inclusion criteria: General Participant Inclusion Criteria 1. Age ≥ 18 years 2. Clear optical media in the studied eye 3. Refractive error not higher than spherical equivalent of 10 D and best corrected visual acuity 4. Equal to 6/24 or better at qualification 5. Women of childbearing potential identified as not pregnant and have consented to complete a pregnancy test 6. Subjects who have personally signed and dated the informed consent document indicating that they have been informed of all pertinent aspects of the study Group Specific Participant Inclusion Criteria Glaucoma Participant Inclusion Criteria: 1. Glaucoma group subjects will show progression in one or more of the parameters measured and will have at least one eye with a diagnosis of glaucoma (abnormal optic disc and/or visual field defect or both); be diagnosed as a glaucoma suspect or ocular hypertensive (elevated IOP) 2. Subjects proven to be able to perform reliable visual field testing using the HFA 640, central 24-2 program, to yield full thresholds, and have had good fundoscopy with assessment of their optic disc AMD Participant Inclusion Criteria: 1. Patients with AMD as defined by: 1.1. Early AMD mainly characterised by drusen, retinal pigment epithelium (RPE) pigment changes 1.2. Late AMD mainly characterised as: geographic atrophy of the RPE (dry AMD) 2. Neovascular AMD (wet AMD) Optic Neuritis Participant Inclusion Criteria: 1. Clinical diagnosis of optic neuritis affecting one eye within two years 2. Visual acuity in affected eye ≤ 6/12 at worst point 3. Corrected vision in unaffected eye ≥ 6/6 4. No history of optic neuritis or other ocular disease in either eye prior to the episode of optic neuritis 5. Subjects proven to be able to perform reliable visual field testing using the HFA 640, central 24-2 program, to yield full thresholds, and have had good fundoscopy with assessment of their optic disc Healthy Volunteers Participant Inclusion Criteria: 1. Confirmation of medical history as confirmed by General Practitioner 2. No evidence of any eye disease |
| Key exclusion criteria | Current exclusion criteria as of 21/06/2017: General Exclusion Criteria are: 1. Presence of severe, unstable or uncontrolled systemic disease 2. Known intolerance to IMP 3. Body weight <40kg or >150kg 4. Inability to comply with the study or follow-up procedures 5. Any subjects with a known history of clotting diseases (including DVTs), and subjects taking anticoagulants 6. Ocular surgery within the past 3 months or planned surgery in the study eye, during the course of the trial 7. Pregnant or lactating, or not using adequate contraception for the duration of the trial (and 30 days post injection of study drug) 8. Currently being treated for cancer or any other disease likely to adversely affect participation in this study 9. AIDS / HIV 10. History of alcoholism or drug addiction 11. History or active uveitis 12. History of systemic vasculitis, collagenosis or ongoing treatment of cancer 13. Evidence of previous retinal vascular disease 14. Individuals with terminal illness, or mental illness affecting their compliance with the study 15. Any other disease, condition or laboratory abnormality that in the opinion of the CI may increase the risk for the participation or may interfere with the interpretation of study results and in the judgement of the Investigator would make the subject inappropriate for entry into the study. 16. Central corneal thickness <450 µm or >650µm 17. Currently, or within the last 3 months, enrolled in a clinical trial of an Investigational Medicinal Product 18. History of retinal laser photocoagulation 19. Media opacities or retinal pathology or amblyopia significantly limiting visual acuity, visual field test or retinal imaging 20. Any other condition or pathological process that in the opinion of the investigator would not make the participant suitable for the trial Group Specific Exclusion criteria are: Glaucoma: 1. Uncontrolled I0P >24mmHg 2. Angle closure/narrow glaucoma. Mean deviation at HVF worse than -12dB Age-related Macular Degeneration: 1. Presence of choroidal neovascularisation (CNVM) 2. Current or past use for more than 30 days of chloroquine, hydroxychloroquine, chlorpromazine, thioridazine, quinine sulfate, clofazimine, cisplatin, carmustine, (BCNU), deferoxamine, amiodarone, isoretinoin, or gold Optic Neuritis: 1. There are no specific exclusion criteria for optic neuritis participants Down’s Syndrome: 1. Clinical diagnosis of dementia or other psychiatric illness 2. Evidence of serious cognitive decline or onset of dementia from historical records 3. Unable to give assent to the study, or unable to have a legal representative give full informed consent Healthy Volunteers: 1. Evidence of any historical retinal eye disease Previous exclusion criteria: General Participant Exclusion Criteria 1. Presence of severe, unstable or uncontrolled systemic disease 2. Known intolerance to IMP 3. Body weight <40kg or >150kg 4. Inability to comply with the study or follow-up procedures 5. Any subjects with a known history of clotting diseases (including DVTs), and subjects taking anticoagulants 6. Ocular surgery within the past 3 months or planned surgery in the study eye, during the course of the trial 7. Pregnant or lactating, or not using adequate contraception* for the duration of the trial (and 30 days post injection of study drug) 8. Currently being treated for cancer or any other disease likely to adversely affect participation in this study 9. AIDS/HIV 10. History of alcoholism or drug addiction 11. History or active uveitis 12. History of systemic vasculitis, collagenosis or ongoing treatment of cancer 13. Evidence of previous retinal vascular disease 14. Individuals with terminal illness, or mental illness affecting their compliance with the study 15. Any other disease, condition or laboratory abnormality that in the opinion of the CI may increase the risk for the participation or may interfere with the interpretation of study results and in the judgement of the Investigator would make the subject inappropriate for entry into the study 16. Central corneal thickness <450 pm or >650pm 17. Currently, or within the last 3 months, enrolled in a clinical trial of an investigational medicinal product 18. History of retinal laser photocoagulation 19. Media opacities or retinal pathology or amblyopia significantly limiting visual acuity, visual field test or retinal imaging 20. Any other condition or pathological process that in the opinion of the investigator would not make the patient suitable for the trial 21. For the purposes of this study, females will be considered of childbearing potential unless they are naturally postmenopausal or permanently sterilised (i.e. hysterectomy). For women of childbearing potential who may participate in the study, the following reliable form of contraception are acceptable (e.g. oral contraceptive and condom, intra--uterine device (IUD) and condom, diaphragm with spermicide and condom) Group Specific Participant Exclusion Criteria Glaucoma Participant Exclusion Criteria 1. Uncontrolled I0P >24mmHg 2. Angle closure/narrow glaucoma. Mean deviation at HVF >12dB AMD Participant Exclusion Criteria 1. Presence of ocular conditions with increased risk of choroidal neovascularisation (CNVM) 2. Current or past use for more than 30 days of chloroquine, hydroxychloroquine, chlorpromazine, thioridazine, quinine sulfate, clofazimine, cisplatin, carmustine, (BCNU), deferoxamine, amiodarone, isoretinoin, or gold Optic Neuritis Participant Exclusion Criteria 1. Corticosteroid use in the past 2 months Healthy Volunteers Participant Exclusion Criteria 1. Evidence of any historical retinal eye disease |
| Date of first enrolment | 08/02/2017 |
| Date of final enrolment | 30/06/2017 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
London
NW1 5QH
United Kingdom
Sponsor information
University/education
Comprehensive Clinical Trials Unit
Gower Street
London
WC1E 6BT
England
United Kingdom
| Phone | +44 20 3108 2385 |
|---|---|
| elizabeth.clark@ucl.ac.uk | |
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Charity
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/08/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal |
| IPD sharing plan | The identity of participants and any personal details will be kept confidential. No named information about the participants will be published in any report of this study. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 02/07/2020 | 22/05/2020 | Yes | No |
| Results article | results | 01/01/2021 | 29/12/2020 | Yes | No |
| Results article | review | 01/01/2022 | 14/11/2022 | Yes | No |
| Dataset | dataset | 19/05/2023 | No | No | |
| Poster results | Abnormal retinal apoptosis morphometry in glaucoma and optic neuritis | 04/05/2023 | 19/05/2023 | No | No |
| Poster results | Characterising DARC (Detecting Apoptosing Retinal Cells) spots in Optic Neuritis (ON) and healthy eyes | 04/05/2022 | 19/05/2023 | No | No |
| Poster results | Characterising DARC (Detecting Apoptosing Retinal Cells) spots in glaucoma and healthy eyes | 04/05/2022 | 19/05/2023 | No | No |
| Protocol file | version 3.0 | 10/11/2016 | 22/05/2023 | No | No |
| HRA research summary | 26/07/2023 | No | No |
Additional files
- ISRCTN10751859_FinalResults.pdf
- dataset
- ISRCTN10751859_Glaucoma_Poster_ARVO_June2022.pdf
- Characterising DARC (Detecting Apoptosing Retinal Cells) spots in glaucoma and healthy eyes
- ISRCTN10751859_OpticNeuritis_Poster_ARVO_June2022.pdf
- Characterising DARC (Detecting Apoptosing Retinal Cells) spots in Optic Neuritis (ON) and healthy eyes
- ISRCTN10751859_GlaucomaOpticNeuritis_Poster_ARVO_June2023.pdf
- Abnormal retinal apoptosis morphometry in glaucoma and optic neuritis
- ISRCTN10751859_Protocol_v3.0_10Nov2016.pdf
Editorial Notes
22/05/2023: Protocol uploaded (not peer reviewed).
19/05/2023: The following changes were made to the trial record:
1. Three posters and the dataset have been added.
2. Removed clinicaltrialsregister.eu link to basic results (scientific).
14/11/2022: Publication reference added.
29/12/2020: Publication reference added.
17/06/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrolment was added.
22/05/2020: Publication reference added.
22/02/2019: Internal review.
20/11/2018: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/10/2017 to 31/08/2018.
2. The intention to publish date was changed from 31/12/2017 to 31/08/2019.
08/11/2017: The ISRCTN prospective/retrospective flag compares the date of registration with the recruitment start date and does not include any grace period. The registration of this study was requested through the NIHR Portfolio and was finalised within 6 months of the recruitment starting.
21/06/2017: Updated study aims, inclusion criteria, and exclusion criteria.
12/04/2017: Verified study information with principal investigator.
