E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Inherited form of eye disease. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
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 | 10038914 |
E.1.2 | Term | Retinitis pigmentosa |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To describe the anatomical and functional changes occurring in treated and control eyes over a 36-month period.
Technical outcome measures = OCT: (1) Change in area of ellipsoid zone integrity (mm2) at the macula. (2) Change in outer retinal thickness across the macula. (3) Change in subfoveal choroidal thickness (mm). FAF: (1) Change in area demonstrating “loss of AF” on standard 55° macula centred image (mm2). (2) Area within the ring of hyperautofluorescence (mm2). Visual Field: Change in size of V4e isopter area.
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E.2.2 | Secondary objectives of the trial |
1. To describe further anatomical and functional changes occurring in treated and control eyes over 36 months.
Technical outcome measures = Retinal Oximetry: Change in oxygen saturation and vessel calibre in retinal venules and arterioles taken at predetermined retinal loci. ERG: Change in all ISCEV electrophysiological parameters - PERG amplitude (P50, N95), rod-specific B wave amplitude, FFERG A and B wave amplitudes and timing, 30Hz flicker amplitude and latency, extent of multifocal ERG change. The hand-held ERG (RETeval) will be used to monitor 30Hz flicker. Microperimetry: Change in mesopic and scotopic threshold sensitivities at predetermined retinal loci. Change in area under the “hill of vision”. Adaptive optics slit lamp ophthalmoscopy: Change in photoreceptor outer segment morphology (Cone density, ratio of hexagonal Voronoi domain, and average nearest neighbour distance (NND)/expected NND - mean value of two independent graders).
2. To study the safety profile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult patients with retinitis pigmentosa and signs of intraocular inflammation (vitreous cells, cataract, epiretinal membrane, intraretinal oedema, clinically significant migration of pigment cells into the retina). |
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E.4 | Principal exclusion criteria |
1. Patients in whom Fluocinolone Acetonide is contraindicated (prior infectious eye disease, glaucoma or steroid induced ocular hypertension). 2. Patients with a clinically apparent asymmetric expression of their retinopathy (as determined by an experienced retina physician). 3. High ametropia (greater than ±6D) to avoid complications of cataract surgery should it be necessary. 4. Patients with planned intraocular surgery within the study period. 5. Patients with dense cataract precluding adequate fundus imaging. 6. Female patients who are pregnant or breastfeeding. Female patients of child-bearing age should ensure an adequate contraceptive measure is used. 7. Patients known to require other forms of systemic immunosuppression within the study period.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome measures: OCT: (1) Change in area of ellipsoid zone integrity (mm2) at the macula. (2) Change in outer retinal thickness across the macula. (3) Change in subfoveal choroidal thickness (mm). FAF: (1) Change in area demonstrating “loss of AF” on standard 55 degree macula centred image (mm2). (2) Area within the ring of hyperautofluorescence (outer edge taken as the limit if a broad band). Visual Field: Change in size of V4e isopter area over 36 months.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline (month 0) Week 2 (safety check of intraocular pressure) Month 4 Month 8 Month 12 Month 24 Month 36 |
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E.5.2 | Secondary end point(s) |
Retinal Oximetry: Change in oxygen saturation and vessel calibre in retinal venules and arterioles taken at predetermined retinal loci. ERG: Change in all ISCEV electrophysiological parameters - PERG amplitude (P50, N95), rod-specific B wave amplitude, FFERG A and B wave amplitudes and timing, 30Hz flicker amplitude and latency, extent of multifocal ERG change. The hand-held ERG (RETeval) will be used to monitor 30Hz flicker. Microperimetry: Change in mesopic and scotopic threshold sensitivities at predetermined retinal loci. Change in area under the “hill of vision”. Adaptive optics slit lamp ophthalmoscopy: Change in photoreceptor outer segment morphology (Cone density, ratio of hexagonal Voronoi domain, and average nearest neighbour distance (NND)/expected NND - mean value of two independent graders).
The safety profile over 36 months of an intravitreal steroid implant (Fluocinolone Acetonide, 0.19mg) in adult patients with retinitis pigmentosa. Outcome measures: Number of cases requiring treatment for either (a) ocular hypertension or glaucoma, (b) cataract or (c) posterior segment disease (retinal detachment, tear or endophthalmitis).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline (month 0) Week 2 (safety check of intraocular pressure) Month 4 Month 8 Month 12 Month 24 Month 36 |
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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 | Yes |
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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
control is the fellow (untreated) eye |
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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 last visit of the last subject undergoing the trial |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |