Prospective, Randomized, Sham-controlled, Dose-finding I/II Trial of Safety and Efficacy of Modified Optogenetic Gene Therapy (ZM-02 Injection)

A Prospective, Randomized, Sham-controlled, Dose-finding Phase 1/2 Two-part Trial to Evaluate the Safety, Tolerability, and Efficacy of ZM-02 Injection in Patients With Advanced Retinitis Pigmentosa

Status

Not yet recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07282457

Acronym

PRISM

Enrollment

Registered

2025-12-15

Start date

2026-06-25

Completion date

2031-12-25

Last updated

2026-04-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Retinitis Pigmentosa (RP)

Keywords

gene therapy, AAV, RP, optogenetics

Brief summary

This is a Phase 1/2, multi-center, randomized, sham-controlled, dose-escalation study evaluating ZM-02 in patients with advanced retinitis pigmentosa (RP).

Detailed description

Retinitis pigmentosa (RP) is the most common inherited retinal disease, characterized by progressive loss of visual function that can lead to severe visual impairment or blindness with no effective treatment. This Phase 1/2 study is designed to evaluate the safety, tolerability, and preliminary efficacy of a single unilateral intravitreal injection of ZM-02 at escalating dose levels in patients with advanced RP. The study includes a sham-controlled design and will assess safety outcomes as well as multiple functional and structural measures of visual performance over long-term follow-up.

Interventions

GENETICZM-02 (low dose)

Single unilateral IVT injection of low-dose ZM-02 in the study eye

GENETICZM-02 (high dose)

Single unilateral IVT injection of high-dose ZM-02 in the study eye

GENETICZM-02 (selected dose)

Single unilateral IVT injection of selected-dose ZM-02 in the study eye

PROCEDURESham injection

Sham IVT procedure in the study eye

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

6 Years to 60 Years

Healthy volunteers

Inclusion criteria

1. Male or female participants aged 6 to 60 years. 2. Clinical diagnosis of advanced retinitis pigmentosa (RP). 3. Best corrected visual acuity at or below the protocol-defined threshold in the study eye. 4. Presence of sufficient retinal structure in the study eye as determined by screening assessments. 5. Ability to understand and sign informed consent (and assent, when applicable).

Exclusion criteria

1. Presence of other ocular conditions that could interfere with study assessments. 2. History of significant ocular surgery in the study eye within a protocol-defined period. 3. Active ocular infection or inflammation. 4. Clinically significant systemic disease that could increase study risk or interfere with assessments. 5. Positive screening for clinically significant infectious diseases, as defined in the protocol. 6. Pregnant or breastfeeding individuals. 7. Any condition that, in the investigator's judgment, would make the participant unsuitable for study participation.

Design outcomes

Primary

Measure	Time frame	Description
Safety and tolerability of ZM-02	Baseline to Week 52.	Incidence of severity of ocular and systemic adverse events (AEs) and serious adverse events (SAEs) following a single intravitreal injection of ZM-02.

Secondary

Measure	Time frame	Description
Change from Baseline in Best-Corrected Visual Acuity (BCVA) of Both Eyes	Baseline to Week 52.	—
Change from Baseline in Functional Vision (MLMT)	Baseline to Week 52.	Change from baseline in the multi-luminance mobility test (MLMT) performance.
Change from Baseline in Vision-Related Quality of Life (NEI VFQ-25)	Baseline to Week 52.	—

Contacts

CONTACTWindy Zhou

zmt@zmtherapeutics.com+86 18986214263

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Apr 14, 2026