An open-label multiple dose safety, tolerability and exploratory efficacy clinical trial of PST-611 in patients with geographic atrophy secondary to age-related macular degeneration

Overview

Sponsor-declared trial summary

Key facts

Sponsor

PulseSight Therapeutics

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Decision date (initial)

2026-06-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate safety and tolerability of multiple doses of PST-611

Secondary objectives 3

1. To assess changes over time in standard ophthalmic examinations, for safety evaluation
2. To assess changes over time in standard ophthalmic examinations, for safety and exploratory efficacy evaluation
3. To assess changes over time in novel visual function and retinal morphology examinations, for exploratory efficacy evaluation

Conditions and MedDRA coding

Geographic atrophy secondary to age-related macular degeneration

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Subjects must give written informed consent, be able to make the required trial visits and follow instructions.
2. Female and male subjects must be 65 years of age or older.
3. In the study eye (SE): cRORA must be present at OCT and attributed to AMD, as evaluated by the Investigator. cRORA is defined on OCT by (1) presence of a region of hypertransmission of at least 250 µm in diameter in any lateral dimension, and (2) presence of a zone of attenuation or disruption of the RPE of at least 250 µm in diameter, and (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear (Sadda et al., 2018). All the above listed criteria are to be met for presence of cRORA.
4. Fixation, either central or eccentric, of both eyes, must be compatible with the performance of the ocular imaging and functional assessments included in the trial, as evaluated by the Investigator. The incapacity to fully perform exploratory assessments or optional exploratory assessments is not a reason for not selecting a subject when all other inclusion and exclusion criteria are met.
5. Participants must be affiliated to social security insurance (if applicable, in accordance with local/applicable regulations).
6. Documented recent history (i.e., over 3 to 12 months prior to first PST-611 administration) of GA lesion area progression, with a yearly growth projection of ≥ 1.6 mm2, in the SE
7. GA lesion area prior to the first PST-611 administration must be between 1.25 mm2 and 16 mm2, as assessed by OCT, in SE. If peripapillary atrophy is present, the GA lesion area must be separate from the peripapillary atrophy and not be expected to merge with the peripapillary atrophy during the trial.
8. If both eyes are eligible, the SE will be selected by the Investigator based on the totality of the clinical evaluation, including, e.g., projected GA lesion area growth rate and ease of treatment administration procedure performance.
9. Best-Corrected Visual Acuity (BCVA) must be ≤ 75 ETDRS letters (Snellen ≤ 20/32) in the SE

Exclusion criteria 15

1. Both eyes (OU): any active intraocular or periocular infection or inflammation (eg, infectious blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis), or history of intraocular or periocular infection or inflammation in the 12 weeks (84 days) prior to Dose 1, the first PST-611 administration.
2. Subject has any condition, which in the opinion of the Investigator, could compromise the subject’s safety or adherence to the trial protocol or follow-up
3. Known/suspected hypersensitivity to any standard of care topical or local analgesics/anesthetics or other standard of care treatments used in the preparation of PST-611 administration procedure.
4. Treatment with investigational medicinal products in the 12 weeks (84 days) prior to Dose 1, the first PST-611 administration.
5. Subjects who lack a sufficient command of French language to give a written informed consent in that language.
6. SE: any intraocular surgery (including cataract surgery) or intravitreal (IVT) or periocular corticosteroid injection in the 12 weeks (84 days) prior to Dose 1, the first PST-611 administration.
7. SE: the documented need for more than 2 anti-VEGF IVT treatments per year as well as any anti-VEGF IVT treatment within 3 months prior to Dose 1, the first dose of PST-611, and lesion must be clinically inactive. A history of wet AMD in the SE is not an exclusion criterion.
8. SE: media opacity that interferes with fundus imaging or is likely to require surgery during the trial period.
9. SE: subject with history of glaucoma filtering surgery (e.g., trabeculectomy or aqueous shunt implant) or who underwent eye surgery in the 12 weeks (84 days) prior to Dose 1, the first PST-611 administration.
10. SE: subject who has uncontrolled intraocular pressure of ≥ 25 mmHg in the SE at the Screening and Trial Baseline (E1) Visits.
11. SE: subject with intraocular hypotension (<6 mmHg) in the SE that in the opinion of the Investigator would interfere with the PST-611 administrations or the evaluation of its safety or efficacy.
12. SE: subject with history of scleritis, scleral thinning, cicatrizing conjunctival diseases, severe ocular allergies, severe ocular surface disease, ocular scarring or intraocular hardware (e.g., retained implant device) that could interfere with the PST-611 administrations or the evaluation of its safety.
13. SE: any other concurrent ocular surface or intra-ocular condition, including retinal disease other than AMD, which, in the opinion of the Investigator, may pose a safety risk for the PST-611 administrations or interfere with the evaluation of its safety.
14. Subject previously exposed to any gene therapy product other than the non- viral gene therapy PST-611.
15. Subject legally incapacitated or having limited legal capacity falling under articles L1121-6 and L1121-8 of French Health Code

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Ocular AEs and TEAEs (incl. SAEs) frequency and severity. • Findings at ophthalmic clinical examination, including slit lamp biomicroscopy and dilated ophthalmoscopy, intraocular pressure (IOP) and best corrected visual acuity (BCVA), color fundus photography (CFP) and Spectral Domain-Optical Coherence Tomography (SD-OCT).

Secondary endpoints 3

1. • Change from Baseline (CFB) in Intraocular pressure (IOP) • CFB in ophthalmic clinical examination including slit lamp biomicroscopy and ophthalmoscopy • CFB in clinical assessment of color fundus photography (CFP) • CFB in clinical assessment of Spectral Domain-Optical Coherence Tomography (SD-OCT
2. CFB in best corrected visual acuity (BCVA)
3. CFB in quantitative Contrast Sensitivity Function (qCSF) at normal luminance (Manifold Platform®) CFB in the area of retinal pigment epithelium (RPE) loss identified by deep learning-based analysis of SD-OCT CFB in the area of photoreceptor (PR) degeneration (also known as EZ layer loss) identified by deep learning-based analysis of SD-OCT

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

PulseSight Therapeutics

Sponsor organisation

PulseSight Therapeutics

Address

2-10 Rue D Oradour Sur Glane

City

Paris

Postcode

75015

Country

France

Scientific contact point

Organisation

PulseSight Therapeutics

Contact name

Thierry Bordet

Public contact point

Organisation

PulseSight Therapeutics

Contact name

Thierry Bordet

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications