LX107 gene therapy for AIPL1-related retinal dystrophy

An Exploratory Clinical Study to Evaluate LX107 Gene Therapy in Patients With AIPL1 Biallelic Mutation-related Inherited Retinal Dystrophy (AIPL1-IRD)

This trial will try a single subretinal injection of LX107 gene therapy in people aged 4 and up with retinal dystrophy caused by two AIPL1 mutations to see if it improves vision and is safe.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 13 (estimated)
• Ages: 4 Years and up
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Academic / other)
• Locations: 1 site (Shanghai)
• Trial ID: NCT07063030 on ClinicalTrials.gov

What this trial studies

This is an early phase 1 interventional trial administering a subretinal injection of LX107 to one investigator-selected study eye in patients with genetically confirmed biallelic AIPL1 retinal dystrophy. Eligible participants are age 4 or older and must have a study eye with best-corrected visual acuity no better than 58 ETDRS letters at baseline. The protocol includes long-term follow-up visits to monitor safety, retinal structure, and visual function following treatment. The primary focus is safety with collection of preliminary efficacy signals in this rare, monogenic cause of retinal degeneration.

Who should consider this trial

Good fit: Ideal candidates are people aged 4 years or older with a confirmed biallelic AIPL1 mutation, who have a study eye with BCVA ≤ 58 ETDRS letters and can consent and comply with long-term follow-up.

Not a fit: Patients without confirmed biallelic AIPL1 mutations, with advanced retinal loss in the study eye, or with other ocular diseases that would interfere with treatment or outcome interpretation are unlikely to benefit.

Why it matters

Potential benefit: If successful, LX107 could preserve or improve photoreceptor function and lead to stabilization or improvement of vision in people with AIPL1-related retinal dystrophy.

How similar studies have performed: Gene therapy has shown clear clinical benefit for other inherited retinal diseases such as RPE65 deficiency, but LX107 for AIPL1 is an early and relatively untested human approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. The subject and/or their guardian signs a written informed consent form and is willing to comply with the long-term follow-up protocol and supporting protocols.
2. Adult or pediatric patients (aged ≥ 4 years) diagnosed with AIPL1-IRD.
3. Definitive molecular diagnosis of biallelic AIPL1 gene mutations confirmed by next-generation sequencing combined with Sanger validation.
4. The study eye has a best-corrected visual acuity of no more than 58 letters (approximately equivalent to decimal visual acuity ≤ 0.3) using the ETDRS visual acuity chart at baseline.

Note: Only one eye will be designated as the "study eye" (i.e., the eye to receive treatment) at the investigator's discretion.

Exclusion Criteria:For any eye with the following conditions:

1. A history of ocular diseases that, in the investigator's judgment, may hinder the planned treatment or interfere with the interpretation of study endpoints (e.g., glaucoma, diabetic retinopathy, retinal vein occlusion, retinal detachment, posterior or panuveitis, etc.).
2. Any eye with a history of gene therapy for IRD or other hereditary neuro-ophthalmic diseases (including but not limited to other viral vector-based gene therapies, mRNA therapies, etc.).
3. A lack of sufficient viable retinal cells as determined by non-invasive methods such as OCT or ophthalmoscopy.
4. Any active intraocular or periocular infection in the study eye (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis).
5. A history of intraocular surgery (e.g., vitrectomy, cataract surgery, trabeculectomy, or other filtering surgery) in the 6 months prior to the screening visit.

   For any systemic conditions:
6. Uncontrolled hypertension, defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg. If the initial measurement exceeds the above limits, it may be repeated on the same day or another day during the screening period; if the subject is taking oral antihypertensive drugs, they must have been on a stable dose of the same drug for at least 30 days prior to screening.
7. Diabetic patients meeting any of the following criteria: ① known to have macrovascular complications; ② baseline HbA1c \> 7.5%; ③ receiving treatment with two or more oral hypoglycemic agents, insulin, or GLP-1 receptor agonists.
8. A history of any other diseases, metabolic disorders, physical examination findings, or clinical laboratory abnormalities that, in the investigator's judgment, may contraindicate the use of the study drug, interfere with the interpretation of study results, or place the subject at high risk of treatment complications, including but not limited to: AIDS, syphilis, acute/chronic active hepatitis B or C, coagulation disorders, a history of treated or untreated malignancy within the past 5 years (except for localized basal cell carcinoma of the skin or in situ cervical cancer), etc.
9. Any of the following laboratory abnormalities: ① platelet count \< 100 × 10⁹/L, hemoglobin (Hb) \< 10 g/dL (males) or \< 9 g/dL (females); ② aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 × ULN; ③ serum creatinine or urea \> 1.5 × ULN.
10. Administration of any other investigational drug (except vitamins and minerals) within 3 months prior to screening, or an attempt to participate in another clinical trial during the study period.
11. Other circumstances deemed unsuitable for enrollment by the investigator.
12. Unwillingness to use effective contraceptive methods during the study; pregnant or lactating women, or women planning to become pregnant or lactate during the study period.

Where this trial is running

Shanghai

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, China (Recruiting)

Conditions Retinal Dystrophy