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 |
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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 | 20.0 |
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 |
The primary objective of the study is to establish the safety of three different doses of hRPC from a single dose administration. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives measure changes in visual function in subjects with RP who underwent surgical implantation of hRPC cells. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must satisfy all of the following criteria to be included in the study: a) Have ability to give written informed consent as evidenced by signature on the subject consent form b) Be adult male or female over 18 years of age c) Have clinical diagnosis of RP, based upon one or more of the following: clinical features, medical imaging, electrophysiological measures and genetic testing, if available. Genetic confirmation is not obligatory. d) Have Best Corrected ETDRS visual acuity of 35 letters or less (approximately 20/200 or worse) in the study eye for cohorts 1-5; have Best Corrected ETDRS visual acuity of 8 letters (approximately 20/800) to 63 letters (approximately 20/63) in the study eye for cohort 6-8, and Best Corrected ETDRS visual acuity of 8 letters (approximately 20/800) to 68 letters (approximately 20/50) for cohorts 9 and onwards e) Be able to complete the entire microperimetry test, and demonstrate adequate fixation and consistency between baseline readings such that the accuracy of both baseline and follow up testing should enable the detection of clinically significant changes in retinal sensitivity. f) Be medically able to undergo vitrectomy and subretinal injection. g) Have good general health as defined by: i. Normal serum chemistry and hematology. Out of normal range laboratory findings deemed not clinically significant (at the discretion of the Investigator) are acceptable. ii. No history of malignancy, except non-melanoma skin cancer; pre-malignant conditions and cancer in situ. iii. Negative serology for human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) iv. Medically fit enough to undergo surgery which may require general anesthesia as well as medically fit to undergo a short perioperative course of systemic corticosteroid therapy v. Free of any other systemic condition that in the opinion of the Investigator may have an impact on the safety of the subject, conduct of study procedures, or integrity of study data (e.g. severe cardiovascular or respiratory disease; poorly controlled diabetes; significant psychiatric impairment) h) Females of childbearing potential must have a confirmed negative pregnancy test at Visits 1 and 3 and be willing to use acceptable method of contraception (e.g. oral contraceptive and condom, intra-uterine device (IUD) and condom, diaphragm with spermicide and condom) for the duration of this study i) Males must be willing to use to use an acceptable method of contraception (e.g. barrier and spermicide) for the duration of this study; unless they have been surgically sterilized with confirmed azoospermia. j) Be willing and able to attend all scheduled clinical assessments, ability to communicate well with the Investigator and to comply with the expectations of the study. |
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E.4 | Principal exclusion criteria |
Subjects must not have any of the following criteria: a) Exhibits a difference in ETDRS BCVA of 15 letters of more in either eye between any of the baseline visits. b) Exhibits a difference in ETDRS BCVA of 20 or more letters between eyes at the time of any of the screening or baseline visits attributed to asymmetry in the progression of RP. c) Presence of ocular disease or ocular media opacity in the study eye, which in the opinion of the Investigator, will preclude an accurate evaluation at any time during the study. d) History of any retinal and/or macular disease other than RP (e.g. retinal detachment) that in the opinion of the Investigator may have an impact on the safety of the subject, conduct of study procedures, or integrity of study data. Specifically, subjects in whom significant pre-existing vitreoretinal pathology might influence visual acuity outcomes should be excluded. e) Active ocular infection or inflammation, or any history of intraocular inflammation, that would expose subject to risk during or following surgery f) Prior vitrectomy in the study eye g) A history of amblyopia in the study eye h) High myopia (>6 diopters) in the study eye i) Cataract surgery in the study eye or ocular surgery in either eye (which in the opinion of the investigator may have an impact on patient safety or the integrity of data from the study eye) during the study or within 3 months prior to treatment. j) Participation in any clinical study involving an investigational drug or device within 6 months prior to treatment or 5 half-lives of the drug (whichever is longer) prior to initiation of treatment k) Prior stem cell administration or injections to any part of the body (subjects who have received autologous stem cell transplant will be eligible) l) Use of systemic immunosuppressive agents (e.g. corticosteroid) in the 6 months prior to treatment or 5 half-lives of the drug (whichever is longer) prior to initiation of treatment (Note: inhaled, intranasal, and/or topical dermatologic steroids are allowed.) m) For females, be breastfeeding or planning a pregnancy n) Known hypersensitivity to any of ingredients of the excipients |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is safety over the six months after treatment as assessed by the incidence of treatment emergent adverse events and changes from baseline in other safety parameters. Safety measures will be assessed by review of important events, including but not limited to inflammation, complications of the surgical procedure and worsening of vision. Anatomical endpoints related to transplant integrity, survival and surgical complications will be measured using: Color fundus photography Fundus autofluorescence Spectral domain-OCT (SD-OCT) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary safety endpoints: There are no specific reference ranges or quantitative changes that are recognised in grading or following RP. Therefore the Principal Investigator will review the data on each of the following tests and assess whether any changes are clinically meaningful and/or may constitute an improvement or adverse event.
Measures of change in visual function: 1. Change in visual acuity A summary of the ETDRS +/- BRVT BCVA letter score and the change from baseline to end of study (24 months) in the treated eye presented by treatment group.
2. Change in visual field: Goldmann visual field, microperimetry and FST A summary of the perimetry and change from baseline to end of study (24 months) in the treated eye presented by treatment group.
3. Change in retinal sensitivity in the area overlying the implanted hRPC as compared with untreated retina. ERG results and change from baseline to end of study (24 months) summarised descriptively and presented by treatment group.
Anatomical endpoints relating to retinal function in implant location: 1. Color Fundus photography A qualitative description of the change in retinal appearance of treated and untreated retinal area in the treated eye from baseline to end of study (24 months) presented by treatment group.
2. Fundus autofluorescence A qualitative description of the change in retinal appearance of treated and untreated retinal area from baseline to end of study (24 months) presented by treatment group.
3. Spectral domain-OCT (SD-OCT) Summary of the overall retinal thickness and change from baseline to the end of study (24 months) of treated retina compared with untreated retina in the treated eye by treatment group.
Summary of the outer nuclear layer thickness and change from baseline to the end of study (24 months) of treated retina compared with untreated retina in the treated eye by treatment group.
Summary of the ellipsoid zone measurement and change from baseline to the end of study (24 months) of treated retina compared with untreated retina in the treated eye by treatment group, if present.
Signal strength will be summarised by treatment group and visit as a measure of quality of the OCT parameter estimates.
Treatment-emergent adverse events (TEAEs) will be summarised for each treatment group. Incidence will be tabulated by MedDRA system organ class (SOC), preferred term (PT), and treatment group. Events will also be summarised by relationship to study drug, severity, seriousness and for AEs leading to study discontinuation.
Clinical and ocular testing (i.e., laboratory testing, vital signs, physical examinations, ECGs, ocular slit lamp and dilated fundus examination) will be summarised at each visit and presented by treatment group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 months after treatment |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | No |
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 | No |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |