Not yet recruitingRare disease

First study of TTX-381 gene therapy safety in patients with eye problems caused by CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2)

InvestigationalNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial focuses on evaluating a gene therapy called TTX-381 for patients with Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), specifically targeting eye-related symptoms. CLN2 is a rare genetic condition that affects the nervous system and causes vision problems. The study aims to test how safe and well-tolerated this new treatment is when given to patients.

The treatment involves a special type of medicine called gene therapy that is injected under the retina (the light-sensitive layer at the back of the eye). The medication, TTX-381, uses a harmless virus called AAV9 to deliver a working copy of the CLN2 gene to the cells in the eye. This treatment is designed to help produce a protein that is missing in patients with CLN2 disease.

During the study, patients will receive the treatment and be monitored for about one year to check for any side effects and changes in their vision. The study will look at various aspects of eye health, including measuring the thickness of different layers in the retina using special eye imaging. Doctors will also collect samples to check how the treatment is working in the body.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial screening and eligibility confirmation
Your eligibility will be evaluated based on specific criteria, including age (between 24 and 84 months), confirmed CLN2 disease diagnosis, and current treatment with cerliponase alfa.
An eye examination will be performed to measure your retinal thickness using specialized imaging (SD-OCT).
Step 2
Pre-treatment assessment
Your eye condition will be thoroughly documented to establish baseline measurements.
Blood samples will be collected to check for anti-AAV9 antibodies.
Step 3
Treatment administration
TTX-381 will be administered as a suspension injection under the retina (subretinal use).
The procedure will be performed by an eye specialist in a clinical setting.
Step 4
Follow-up period - Day 90
An eye examination will be performed to collect fluid samples from your eye.
The samples will be tested to measure TTX-381 TPP1 levels.
Step 5
Follow-up period - Day 180
Your eye will be examined using imaging technology to measure changes in your retina.
The specialist will assess the photoreceptor layer thickness and other eye measurements.
Step 6
Follow-up period - Day 360
A comprehensive evaluation will be performed to assess your eye condition.
Additional fluid samples will be collected to measure TTX-381 TPP1 levels.
Any side effects or reactions will be documented throughout the year.
Step 7
Long-term monitoring
Regular check-ups will continue according to the study schedule for up to 5 years.
Samples of urine and tears will be collected periodically to test for the presence of TTX-381.

Who can join the trial?

13 criteria

Age must be between 24 months and 84 months (2-7 years old)
Must have genetic mutations affecting both copies of the CLN2 gene
Must have reduced TPP1 enzyme activity in white blood cells
Must show signs of CLN2 disease such as:
- Developmental delays
- Loss of previously gained skills
- Seizures
- Vision problems
- Must be currently receiving cerliponase alfa treatment every two weeks
- Must have specific eye measurements as confirmed by special imaging:
  - Retinal thickness between 140 and 210 micrometers in both eyes
  - Must be willing to follow the study plan for 5 years
  - Parents or legal guardians must provide written consent
  - If sexually mature:
    
    Must agree to use approved birth control methods during the study and for 6 weeks after treatment
    May qualify if previously treated with TTX-381 and met requirements at time of treatment

Who cannot join the trial?

12 criteria

Having any severe eye conditions other than those related to CLN2 disease (a rare genetic disorder affecting the nervous system)
Being younger than 2 years old
Having participated in another clinical trial within the past 30 days
Having known allergies to similar medications
Having uncontrolled seizures or severe neurological symptoms
Having significant medical conditions that could interfere with the study procedures
Being unable to comply with study visits and procedures
Having received gene therapy or similar treatments for CLN2 disease in the past
Being pregnant or breastfeeding (for female participants)
Having laboratory test results outside of acceptable ranges for the study
Having any surgical procedures planned during the study period
Having a history of non-compliance with medical treatments

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Investigated drugs

TTX-381 is an experimental gene therapy product designed to treat eye problems in people with CLN2 disease, also known as neuronal ceroid lipofuscinosis type 2. This therapy aims to deliver genetic material directly to the eye to help treat vision problems associated with this rare genetic condition. Gene therapy works by introducing functional genes to replace or supplement non-working genes in the patient's cells.

TTX-381

What is already known about the treatment

TTX-381 - An experimental gene therapy medication being investigated for treating ocular symptoms of CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2). It is currently in first-in-human clinical trials to evaluate its safety and tolerability in patients with CLN2-related eye problems. While the exact mechanism of action is still being studied, TTX-381 is designed to deliver therapeutic genes to address the underlying genetic cause of vision problems in CLN2 disease. The medication represents a novel therapeutic approach in ophthalmology and neurology, being evaluated through a dose-escalation study with a 360-day follow-up period.

Investigated diseases

Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) - A rare genetic disorder that primarily affects the nervous system and eyes. The condition is caused by the lack of an enzyme called TPP1, which leads to the buildup of substances called lipofuscins in the body's tissues. In the eyes, this accumulation causes progressive vision problems and can lead to vision loss. The disease typically begins between ages 2 and 4, with symptoms gradually becoming more noticeable over time. The condition affects the retina, which is the light-sensitive tissue at the back of the eye, particularly impacting the photoreceptor cells and a layer called the ellipsoid zone.