RPE65 Gene Therapy （LX101）for Leber's Congenital Amaurosis

Leber Congenital Amaurosis Clinical Trial

Official title:

Safety and Efficacy of LX101(AAV2-RPE65) in Patients With Leber's Congenital Amaurosis: a Randomised, Controlled, Open-label, Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04731883
• Other study ID #: Shanghai1st-LX101
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2021
• Est. completion date: June 1, 2023

Study information

• Verified date: January 2021
• Source: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: Huixun Jia, Master
• Phone: 86-18017317575
• Email: jiahuixun[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether gene transfer(LX101) will be safe and effective in the treatment of Leber Congenital Amaurosis (LCA).

Description:

Leber Congenital Amaurosis (LCA)is a severe early onset retinal degeneration. Diagnosis is usually made during the first few months of life in infants who present with severely impaired vision, abnormal eye movements (nystagmus) and abnormal electroretinograms (ERG) indicating decreased retinal function. There is an inevitable progression to total blindness in these individuals due to death of photoreceptor cells. There is presently no treatment for this disease. The primary objective of this study is to determine the safety and tolerability of subretinal administration of Lx101(AAV2-RPE65) to subjects with LCA due to confirmed biallelic RPE65 mutations.

The secondary objective is to assess the objective clinical measures of efficacy in human subjects.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 9
• Est. completion date: June 1, 2023
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 80 Years

Eligibility

Inclusion Criteria:

Age 4 years old or older at the time of administration; Diagnosed with LCA; Molecular diagnosis of LCA due to RPE65 mutations (homozygotes or compound heterozygotes) by a qualified laboratory; Visual acuity = 20/200 or visual field less than 20 degrees in the eye to be injected; Must be willing to adhere to protocol and companion protocol for long-term follow-up as evidenced by written informed consent or parental permission and subject assent.

Exclusion Criteria:

Unable or unwilling to meet requirements of the study; Participation in a clinical study with an investigational drug in the past six months; Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints (for example, glaucoma, corneal or lenticular opacities); Lack of sufficient viable retinal cells as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Specifically, if indirect ophthalmoscopy reveals less than 1 disc area of retina which is not involved by complete retinal degeneration (indicated by geographic atrophy, thinning with tapetal sheen, or confluent intraretinal pigment migration), these eyes will be excluded. In addition, in eyes where optical coherence tomography (OCT) scans of sufficient quality can be obtained, areas of retina with thickness measurements less than 100 um, or absence of neural retina, will not be targeted for delivery of LX101(AAV2-RPE65); Complicating systemic diseases or clinically significant abnormal baseline laboratory values.

Prior ocular surgery within six months. Known sensitivity to medications planned for use in the peri-operative period. Individuals of childbearing potential who are pregnant or unwilling to use effective contraception for the duration of the study.

Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.

Related Conditions & MeSH terms

• Blindness
• Leber Congenital Amaurosis

Intervention

Drug:
• Gene therapy-LX1010(AAV2-RPE65)
Subjects will be dosed unilaterally (one eye) injected with AAV2-hRPE65v2 by means of a subretinal injection. Participants randomly assigned to the intervention group received 1 mg/kg per day of prednisone orally for 7 days, at a maximum dose of 40 mg/day regardless of weight, beginning 3 days before their first injection.

Locations

Country	Name	City	State
China	Shanghai General Hospital	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Full-field light sensitivity threshold (FST)	The primary efficacy endpoint, designed to measure the effect of intervention on functional vision, was the change in FST testing.FST measures the lowest illumination perceived-light sensitivity-over the entire visual field, is therefore unaffected by nystagmus, and is useful over a wide range of visual impairment. FST test-retest variability has been stated as 0·3 log and a meaningful change has been suggested as 10 dB or 1 log.	30, 90, 180, and 365 days