Safety and Efficacy Study of Novel Gene Therapy ZM-02 for Retinitis Pigmentosa Patients

Early Phase 1

Recruiting

• Conditions: Retinitis Pigmentosa
• Interventions: Drug: ZM-02-L; Procedure: ZM-02-S; Drug: ZM-02-H

• Registration Number: NCT06292650
• Lead Sponsor: Zhongmou Therapeutics

Brief Summary

This is zM-02's safety, tOlerability, and efficacy in retinitis pigmentOsa first-in-humaN study (MOON). This trial is meant to evaluate the safety and efficacy of ZM-02 in Retinitis pigmentosa (RP) patients. Unilateral intravitreal injections (IVT) will be given into the subject's Study Eye.

Detailed Description

Retinitis pigmentosa (RP) is the most common inherited retinal disease. Individuals affected by RP often experience progressive visual impairment, potentially leading to legal blindness. There is currently no established effective clinical treatment available. We developed an innovative adeno-associated virus (AAV)-based gene therapy for individuals with RP, regardless of their causative mutations. Eight to twelve subjects with RP will be recruited and six to nine of them will receive a single unilateral intravitreal injection of ZM-02 at ascending doses, while two to three receive sham injections as the control group.

Study Timeline

• Study Start: 2024-02-25
• Study First Submitted: 2024-02-27
• Study First Submitted QC: 2024-02-27
• Study First Posted: 2024-03-05
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-13
• Primary Completion: 2027-12-25
• Study Completion: 2028-12-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Patients who meet all of the following criteria can be selected as subjects:

1. Clinically diagnosed with retinal pigment degeneration
2. The vision of the eye being tested is no better than the index value, while the vision of the opposite eye is not better than that of the tested eye
3. The subject has had visual experience above the index value
4. In the OCT examination of the tested eye, the disappearance of the ellipsoid zone is observed, but the inner nuclear layer and the nerve fiber layer of the retina are still present
5. The refractive power of the tested eye is between -6.00 D and +6.00 D
6. Not infected with the Human Immunodeficiency Virus (HIV) and other acute and chronic infectious diseases
7. Voluntarily sign an Informed Consent Form (ICF), and the age is not less than 18 years and not more than 65 years
8. Able to fully understand and agree to cooperate with the implementation of the research protocol

Exclusion Criteria

Subjects who meet any one of the following exclusion criteria will be excluded from the study:

1. Pregnant women, breastfeeding women, or male and female subjects who do not agree to contraception during the 12 months before and after medication
2. Subjects with narrow anterior chamber angles or any other medical conditions that contraindicate pupil dilation
3. Subjects allergic to corticosteroids, who are unable to tolerate the corticosteroid treatment described in the protocol, or have active 4. concurrent infections that contraindicate treatment
4. Subjects with systemic diseases, or other medical or mental illnesses, or other safety concerns for the study
5. Subjects with other symptoms and/or diseases or conditions that can alter visual function, including but not limited to glaucoma and central nervous system lesions (mild cataracts are not included in this restriction)
6. Eye diseases that may interfere with the assessment of vision during the study and/or interfere with other ocular assessments such as OCT
7. Diseases that may affect the clinical trial, such as tumors, metabolic, immune-related diseases, etc.
8. Subjects who have undergone major eye surgery within the last 3 months before screening
9. Subjects with a history of malignant tumors within the last 5 years
10. Subjects with other retinal diseases not suitable for this study, such as retinal detachment
11. Patients undergoing or potentially undergoing immunosuppressive treatment for other diseases, excluding this study
12. Participation in any clinical trials other than this study within the last 3 months
13. Subjects who have received gene therapy outside of this study
14. Other reasons deemed by the researcher as unsuitable for participation in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
group 1	ZM-02-L	IVT administration of a single low dose ZM-02 injection
group 3	ZM-02-S	Sham IVT injection
group 2	ZM-02-H	IVT administration of a single high dose ZM-02 injection

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events and serious adverse events	baseline to day 3, week 1, 4, 16, 24, 36, 52	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment.; A serious adverse event (SAE) is any untoward medical occurrence at any dose that leading to the following: Results in death; Life-threatening, refers to an event in which the patient is at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe; Significant or permanent disability/incapacity, where disability refers to a serious disruption and damage of a person's ability to perform normal life functions; Requires inpatient hospitalization or prolongation of existing hospitalization; Congenital anomaly or birth defect; Other medically important events.
Changes in intraocular pressure (IOP) in Subjects	baseline to day 3, week 1, 4, 16, 24, 36, 52	IOP refers to the fluid pressure inside the eye. Monitoring IOP ensures that interventions do not inadvertently increase IOP to dangerous levels. IOP will be measured using a clinical tonometry device.

Secondary Outcome Measures

Name	Time	Method
Change of FST outcome	baseline to day 3, week 1, 4, 16, 24, 36, 52	The Full Stimulus Test (FST) is a test to assess the functional integrity of the entire visual pathway, from the retina to the visual cortex. It often used in studies involving retinal dystrophies or certain neuro-ophthalmological conditions, FST might be used to assess the efficacy of a treatment or intervention.
Change of MLMT level	baseline to day 3, week 1, 4, 16, 24, 36, 52	Multi-Luminance Mobility Test (MLMT) is used to evaluate how well individuals with visual impairments can navigate and perform tasks in different lighting conditions. This test is particularly relevant for conditions that affect night vision or light adaptation, such as retinitis pigmentosa or other forms of inherited retinal dystrophies.
Change of Quality of Life	baseline to day 3, week 1, 4, 16, 24, 36, 52	Quality of Life will be measured using Visual Function Questionnaire (VFQ-25) or other similar questionnaires before and after treatment

Trial Locations

Locations (1)

Beijing Tongren Hospital of Capital Medical University; 🇨🇳 Beijing, Beijing, China