E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Choroideremia - a currently incurable retinal degeneration caused by null mutations in the CHM gene encoding REP1 protein located on the X chromosome. The condition causes blindness in males by the third or fourth decade. |
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E.1.1.1 | Medical condition in easily understood language |
Choroideremia is a genetically inherited incurable eye disease which affects predominantly men. The disease causes progressive loss of peripheral vision and finally loss of central vision. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008791 |
E.1.2 | Term | Choroideremia |
E.1.2 | System Organ Class | 100000004853 |
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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 |
To assess the effectiveness (with respect to preservation of visual function and retinal structure) and safety of a single injection of the gene therapy product into the back of the eyes of patients with a confirmed diagnosis of choroideremia. The effectiveness and safety of the gene therapy product will be evaluated by various tests conducted regularly for a period of 2 years following treatment. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Candidate is willing and able to give informed consent for participation in the study. • Male aged 18 years or above. • Genetic or molecular confirmed diagnosis of choroideremia (REP1 protein deficiency). • Active disease visible clinically within the macula region. • Best corrected visual acuity equal to or worse than 6/6 (20/20; Decimal 1.0; LogMAR 0) but better than or equal to 6/60 (20/200; Decimal 0.1; LogMAR 1.0) in the study eye. |
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E.4 | Principal exclusion criteria |
• Any female, or a male aged below 18 years. • An additional cause for sight loss (e.g. amblyopia) in the eye to be treated. • Any other significant ocular and non-ocular disease or disorder which, in the opinion of the investigator, may put the participants at risk because of participation in the study. • Inability to take systemic prednisolone for a minimum of 3 weeks. • Unwillingness to use barrier contraception methods for a period of three months following gene therapy surgery, if relevant. • Participation in another research study involving an investigational product in the preceding 12 weeks. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in best corrected visual acuity in the treated eye. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Regular tests over a period of 24 months following gene therapy. |
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E.5.2 | Secondary end point(s) |
Change from baseline in the central visual field in the treated eye as determined by microperimetry.
Change from baseline in the area of surviving RPE in the treated eye as measured by fundus autofluorescence, compared to the untreated fellow eye (control eye) after randomisation of treatment to one eye or the other.
Change from baseline in other functional and anatomical outcomes in the treated eye pertaining to vector efficacy and safety, and safety of the subretinal injection procedure.
Change from baseline in immunological and physiological outcomes pertaining to vector safety. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Regular tests over a period of 24 months following gene therapy. |
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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 | Yes |
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 |
Untreated fellow eye of patient |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
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 | Yes |
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 trial ends at the 24 month follow-up visit of the last of the 30 patients injected with vector |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |