E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glaucoma, Age-related Macular Degeneration, and Optic Neuritis.
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047560 |
E.1.2 | Term | Visual field perimetric tests |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10018307 |
E.1.2 | Term | Glaucoma and ocular hypertension |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021948 |
E.1.2 | Term | Infiltration intravenous injection |
E.1.2 | System Organ Class | 100000004867 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057208 |
E.1.2 | Term | Optical coherence tomography |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071129 |
E.1.2 | Term | Neovascular age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064930 |
E.1.2 | Term | Age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10047566 |
E.1.2 | Term | Visual field tests |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009034 |
E.1.2 | Term | Chronic open angle glaucoma |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030942 |
E.1.2 | Term | Optic neuritis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006027 |
E.1.2 | Term | Borderline glaucoma |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030043 |
E.1.2 | Term | Ocular hypertension |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006028 |
E.1.2 | Term | Borderline glaucoma (glaucoma suspect) |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004571 |
E.1.2 | Term | Bilateral optic neuritis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012121 |
E.1.2 | Term | Defect visual field (NOS) |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020422 |
E.1.2 | Term | HRT |
E.1.2 | System Organ Class | 100000004865 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018304 |
E.1.2 | Term | Glaucoma |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048541 |
E.1.2 | Term | Intravenous catheter management |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary outcome is the efficacy of the intervention ascertained by the DARC Count, which is the number of apoptosing retinal cells visualised 4 hours after the ANX776 injection in patients with Glaucoma, Age-related Macular Degeneration, Optic Neuritis and in Healthy volunteers.
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the response in terms of safety and tolerability of ANX776 in patients with Glaucoma, Age-related Macular Degeneration, Optic Neuritis, and in Healthy volunteers. Safety is defined as absence of an adverse event of grade 3 or above in the study groups. Safety will be measured by adverse events following the Common Terminology Criteria for Adverse Events (CTCAE) scale.
In addition, in a subset of patients, an exploratory secondary objective is to assess if the ANX776 signal is detected in the brain using functional near-infrared spectroscopy (fNIRS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 and best corrected visual acuity equal to 6/24 or better at qualification. 4. Women of childbearing potential identified as not pregnant and have consented to complete a pregnancy test. 5. Subjects who have capacity to consent, and are willing to personally sign the informed consent document indicating that they have been informed of all pertinent aspects of the study.
Group Specific Inclusion criteria are: Glaucoma: 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 10P). 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.
Healthy Volunteers: 1. Confirmation of medical history as confirmed by General Practitioner. 2. No evidence of any eye disease
Exploratory Optional fNIRS Inclusion Criteria: 1. Participants who are bald, or with short (less than 3cm), fair (unpigmented) hair
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E.4 | Principal exclusion criteria |
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, lactating, or premenopausal. 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. Central corneal thickness <450 pm or >650pm. 16. Currently, or within the last 3 months, enrolled in a clinical trial of an Investigational Medicinal Product. 17. History of retinal laser photocoagulation. 18. Media opacities or retinal pathology or amblyopia significantly limiting visual acuity, visual field test or retinal imaging. 19. 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.
Group Specific Exclusion criteria are: Glaucoma: 1. Uncontrolled I0P >24mmHg. 2. Angle closure/narrow glaucoma. Mean deviation at HVF >12dB.
Age-related Macular Degeneration: 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: 1. Corticosteroid use in the past 2 months.
Healthy Volunteers: 1. Evidence of any historical retinal eye disease.
Exploratory Optional fNIRS Exclusion Criteria: 1. There are no specific exclusion criteria for the exploratory optional fNIRS.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is the DARC Count in each eye 4 hours post injection. A log(x+1) transformation will be used for the statistical analysis. Geometric means and 95% confidence intervals will be used to summarise the log(x+1) DARC counts, back transformed to the original measurement scale. A regression model will be fitted to estimate the difference between each affected group and the healthy control group. The regression model will include patient as a random effect.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During injection 15 min post injection 2 hours post injection 4 hours post injection
Retinal imaging will be utilised to visualise apoptosing retinal ganglion cells at above time intervals; corresponding DARC counts inclusive of their means and standard deviations will be reported. |
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E.5.2 | Secondary end point(s) |
Secondary outcome is the number and severity of adverse events. The overall number of adverse events will be reported, stratified by patient group, and categorised according to their nature and severity.
For the Near-infrared spectroscopy, the outcome measure will be the detection of the NIR fluorescent signal in the brain. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During injection 15 min post injection 2 hours post injection 4 hours post injection
30 days post injection - safety telephone call (adverse events only).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will be defined as resolution of all data queries following the last visit by the last participant. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 1 |