ZVS106e subretinal injection for Stargardt disease from two ABCA4 mutations

A Preliminary Clinical Study on the Safety and Efficacy of the Gene Replacement Drug ZVS106e in the Treatment of Hereditary Retinal Degeneration (IRDs) Caused by ABCA4 Biallelic Mutations

This treatment will try a single subretinal injection of ZVS106e in one eye to see if it's safe and may help people aged 8 and older with Stargardt disease caused by two ABCA4 mutations.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 8 Years and up
• Sex: All
• Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University (other)
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT07241169 on ClinicalTrials.gov

What this trial studies

This early-phase 1 interventional study gives a single monocular subretinal injection of ZVS106e to patients with hereditary retinal degeneration caused by biallelic ABCA4 mutations. The primary aim is to collect preliminary safety data after the injection, while secondary and exploratory endpoints will track changes in retinal structure and visual function. Efficacy signals will be explored both in the injected eye and by comparing the non-injected eye to baseline measurements. Participants will be recruited at major ophthalmic centers in China and will undergo scheduled imaging and functional testing during follow-up.

Who should consider this trial

Good fit: People aged 8 or older with genetically confirmed biallelic ABCA4 mutations, a target eye best-corrected visual acuity between 0.5 and 2.0 LogMAR, and who can consent and comply with follow-up (including required contraceptive measures) are ideal candidates.

Not a fit: Patients with other macular lesions such as retinal schisis or epiretinal membrane, other ocular diseases that would hinder surgery or interfere with outcome interpretation, or those outside the specified visual acuity range are unlikely to receive benefit from this intervention.

Why it matters

Potential benefit: If successful, ZVS106e could preserve or improve retinal structure and visual function in affected eyes and slow disease progression.

How similar studies have performed: ABCA4-targeted therapies remain largely experimental; related retinal gene- and cell-based approaches have shown early promise but ABCA4-specific clinical success has been limited so far.

Eligibility criteria

Inclusion Criteria:

1. Age ≥8 years old;
2. Patients diagnosed with hereditary retinal degeneration caused by ABCA4 biallelic mutations through genetic testing, and without other ophthalmic genetic diseases;
3. The target eye must meet the following requirements: the best corrected visual acuity is 0.5 to 2.0 LogMAR (including 0.5 and 2.0 LogMAR, equivalent to the decimal visual acuity index up to 0.3);
4. The subject and his or her spouse agree to take effective contraceptive measures during the trial period and for at least one year after administration.
5. Voluntarily participate in clinical trials and sign informed consent forms, and be able to complete all trial processes as required by the protocol.

Exclusion Criteria:

1. The researchers determined that the target eye currently has or has previously had other macular lesions such as retinal schisis or epiretinal membrane. Or have other eye diseases that may hinder the surgery or interfere with the interpretation of the study endpoint;
2. Having received drug treatment that may affect the observation of the trial within the three months prior to screening;
3. The target eye has undergone the following intraocular surgeries: retinal repositioning and vitrectomy;
4. There are known eye/visual diseases, disorders or lesions that cause or are related to vision loss, or whose related treatments or therapies are known to cause or are related to vision loss;
5. Having suffered from a viral infectious disease that may affect the efficacy and safety evaluation of the investigational drug or having received an antiviral vaccine within one month prior to enrollment;
6. Systemic medications that are currently in use or may be required to cause eye toxicity, such as psoralen, risselinic acid or tamoxifen, etc.
7. Known to be allergic to the drugs planned to be used in the study;
8. Suffering from poorly drug-controlled hypertension: systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg;
9. The following laboratory test abnormalities have clinical significance:

   Liver function: Chronic liver disease, elevation of ALT or AST \>2 times the upper limit of the normal value; Those with abnormal coagulation function (prothrombin time ≥ 3 seconds above the upper limit of the normal value, activated partial thromboplastin time ≥ 10 seconds above the upper limit of the normal value); Serum virological examination: Positive for active hepatitis B, hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or syphilis antibody;
10. There is any past or current medical history that may affect the safety of the trial or the in vivo process of the drug, especially a history of diseases such as cardiovascular, liver, kidney, endocrine, digestive tract, lung, nervous, hematological, tumor, immune or metabolic disorders that the investigators consider to have clinical significance;
11. Those who have participated in any clinical trials of drugs or medical devices within the three months prior to screening;
12. Pregnant or lactating women; According to the researcher's judgment, those who are deemed unsuitable to participate in this clinical trial for other reasons

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Peking University Third Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Zhongshan Ophthalmic Center, Sun Yat-sen University — Guangzhou, Guangdong, China (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: lin Lv, M.D — PI
• Study coordinator: dayou Ding

Conditions: Stargardt, ZVS106e