Safety and Efficacy of a Unilateral Subretinal Administration of HORA PDE6B in Patients with Retinitis Pigmentosa Harbouring Mutations in the PDE6B Gene Leading to a Defect in PDE6ß Expression

eyeDNA Therapeutics1 site in 1 country23 target enrollmentMay 17, 2024

Overview

Phase: Phase 1/2
Intervention: Not specified
Conditions: Not specified
Sponsor: eyeDNA Therapeutics
Enrollment: 23
Locations: 1
Primary Endpoint: Primary endpoints will be the assessment of safety parameters: routine ophthalmic examination, intraocular inflammation, chorioretinal tolerance, questionnaire, vital signs, laboratory measurements
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To assess the safety of a unilateral subretinal administration of HORA-PDE6B

Registry

euclinicaltrials.eu

Start Date

May 17, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

eyeDNA Therapeutics

Responsible Party

Principal Investigator

Chief Development Officer

Scientific

eyeDNA Therapeutics

Eligibility Criteria

Inclusion Criteria

•Patients (male or female) having retinitis pigmentosa (RP) caused by defect in rod cGMP phosphodiesterase 6 (PDE6B) gene without other syndromic manifestations, referred to thereafter as PDE6B RP
•Patients having a phenotypic clinical status established by: a. Disease history; b. Presence of characteristic features of retinitis pigmentosa in fundus; c. Reduction of both rod and cone ERG responses in full-field ERG, with predominance of rod involvement, and with the exception of Cohort #4 (multifocal ERG not done) relative preservation of ERG responses of the fovea in multifocal ERG; d. Best-corrected visual acuity (BCVA) score of ≤60 ETDRS letters (corresponding to ≤0.32 or 20/63 Snellen equivalent) for Cohort #1, ≤ 75 ETDRS letters (corresponding to ≤0.63 or 20/32 Snellen equivalent) for Cohort #2 and a conserved central visual field of at least 10 degrees in every meridian using a V4 stimulus in the study eye for Cohort #3 and ≤75 ETDRS letters (corresponding to ≤0.63 or 20/32 Snellen equivalent). For Cohort #4, an unlimited BCVA score and with a conserved central visual field of at least 10 degrees for the two first adult patients and of at least 20 degrees for all other patients in every meridian using a V4 stimulus in the study eye
•Patients with at least one pathogenic mutant PDE6B allele on each chromosome confirmed by direct sequencing and co-segregation analysis within the patient's family in a certified laboratory
•Adult patients who have given informed consent, and patients under the age of 18 years who have given their assent, and whose both parents/legally designated representatives have provided their informed consent, after having been counselled by the investigator, particularly on the high number of visits and on the requirement of a short hospitalisation
•Patients having a RP aged ≥18 years old for Cohorts #1 to #3; ≥13 years old for Cohort #4
•Patients still having a residual central retinal function that allows ambulation.
•For females (including minors) with childbearing potential, a negative urine pregnancy test at screening (Visit 1/Day -120 to Day -7) and at visit 2 (Day -1). Females (including minors) with childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile) must be using a highly and effective method of contraception (e.g., hormonal birth control, IUD, double barrier [male condom, female condom, diaphragm]) plus a spermicidal agent [contraceptive foam, jelly, or cream], bilateral tubal occlusion, vasectomised partner, sexual abstinence). The patient will be requested to continue the contraception for six months after surgery (Visit 9/Day 180)
•For males of reproductive potential, agreement to use effective contraception for 6 months after administration of the IMP, for sexual activity that could lead to pregnancy
•Patients affiliated to the health security system or covered by national healthcare insurance system as required if non-French citizens

Exclusion Criteria

•Non-inclusion criteria related to co-morbidities
•Patients with chronic conditions such as haematological, cardiac, renal diseases.
•Patients with a clinically significant cardiac disease on routine clinical examination (history, physical examination), or known congestive heart failure, myocardial infarction, clinically significant valvular heart disease, clinically significant cardiac rhythm or conduction abnormalities, uncontrolled or unstable hypertension within 6 months prior to Day
•Patients with pulmonary dysfunction or severe obstructive pulmonary disease that, in the investigator's judgment, could interfere with the study participation and completion.
•Patients with suspected rheumatoid arthritis or any other systemic autoimmune disease.
•Patients with active cancer or patients currently undergoing therapy for cancer.
•Patients with unstable endocrine disease, including unstable diabetes or thyroid disease.
•Patients with alanine transaminase (ALAT), aspartate transaminase (ASAT), or gamma glutamyl transferase (GGT) >3x upper limit of normal.
•Patients with severe anaemia (haemoglobin <9 g/dL), leukopenia (while blood cell count (WBC) <2,500/mm3), thrombocytopenia (platelet count <80,000/mm3), polycytemia (haematocrit >54% [male] or haematocrit >49% [female]) or clinically significant coagulopathy
•Non-inclusion criteria related to infections or immune suppression

Outcomes

Primary Outcomes

Primary endpoints will be the assessment of safety parameters: routine ophthalmic examination, intraocular inflammation, chorioretinal tolerance, questionnaire, vital signs, laboratory measurements

Secondary Outcomes

Functional tests: •distance and near visual acuity and refraction (near visual acuity not applicable for Cohort #4 patients); •colour vision; •visual fields; •global or full-field ERG; multifocal ERG*; •pupillometry (not applicable for the Cohort #3 & Cohort #4 patients); •microperimetry; •mobility test; •dark adaptation test; •full-field sensitivity threshold for the Cohort #3 & Cohort #4 patients; •evaluation of quality of life in adult patients
Morphologic tests: •fundus autofluorescence; •spectral domain optical coherence tomography (SD-OCT)
Exploratory assessment: functional magnetic resonance imaging (fMRI)* * Not to be performed in Cohort #4