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

Retinitis Pigmentosa Clinical Trial

— ZM-02  

Official title:

Prospective, Dose-Escalating, Investigator Initiated Trial to Evaluate the Safety and Efficacy of ZM-02 in Retinitis Pigmentosa

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06292650
• Other study ID #: ZM-02
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: February 25, 2024
• Est. completion date: December 25, 2028

Study information

• Verified date: February 2024
• Source: Zhongmou Therapeutics
• Contact: Pei Cao
• Phone: +86 18707134160
• Email: zmt[@]simbaeye.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: December 25, 2028
• Est. primary completion date: December 25, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa

Intervention

Drug:
• ZM-02-L
rAAV-PsCatCh2.0 intravitreal injection of low dose
• ZM-02-H
rAAV-PsCatCh2.0 intravitreal injection of high dose

Procedure:
• ZM-02-S
sham intravitreal injection of ZM-02 (not actual injection)

Locations

Country	Name	City	State
China	Beijing Tongren Hospital of Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Zhongmou Therapeutics

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in best corrected visual acuity (BCVA)	BCVA of both eyes will be assessed using the early treatment of diabetic retinopathy study (ETDRS) chart or tumbling "E" chart or other avaliable measurement. This approach was chosen to facilitate visual acuity testing in subject who cannot recognize letters.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Other	Change in visual field (VF)	Visual field will be assessed by Humphrey perimetry, changes in VFI, MD, PSD will be analyzed.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Other	Change in Fundus Autofluorescence (FAF)	FAF is a non-invasive imaging technique that provides critical information about the health of the retina, which is vital for the functioning of the retina.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Other	Change in central foveal thickness (CFT) using Optical Coherence Tomography (OCT)	Central Foveal Thickness refers to the thickness of the retina at the fovea, the central part of the macula. Changes in CFT can indicate various retinal conditions, including macular edema, macular degeneration, and central serous retinopathy.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Other	Change in central macular thickness (CMT) using Optical Coherence Tomography (OCT)	Central Macular Thickness is the measurement of the thickness of the macula, which includes the fovea and the small surrounding area. The macula is responsible for central vision and visual acuity.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Other	Changes in the fundus using fundus color photography	Fundus photography is used to document and monitor changes in the eye over time. It's vital for assessing the conditions of retina and monitoring the effects of treatments.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Primary	Incidence of adverse events and serious adverse events	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.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Primary	Changes in intraocular pressure (IOP) in Subjects	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.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Secondary	Change of FST outcome	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.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Secondary	Change of MLMT level	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.	baseline to day 3, week 1, 4, 16, 24, 36, 52
Secondary	Change of Quality of Life	Quality of Life will be measured using Visual Function Questionnaire (VFQ-25) or other similar questionnaires before and after treatment	baseline to day 3, week 1, 4, 16, 24, 36, 52