Actively Recruiting
A First-in-Human, Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of Gene Therapy With TTX-381 for the Ocular Manifestations Associated With Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease
Led by Tern Therapeutics, LLC · Updated on 2025-12-18
16
Participants Needed
2
Research Sites
260 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating TTX-381, a gene therapy, in a first-in-human, open-label study to treat eye problems caused by Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), also known as Batten disease. This condition results from a faulty gene causing lack of an important enzyme, leading to damage in the brain, spinal cord, and eyes, affecting vision and other functions. The study aims to understand the safety and tolerability of TTX-381 to address these ocular issues in affected children. Participants will receive a single dose of TTX-381 injected under the retina of one eye, while the other eye will serve as a control for comparison. The study includes several dose levels, such as 2×10^10 and 6×10^10 genome copies per eye, with an expansion group receiving the lower dose as determined by an independent committee. This dose-escalation design helps researchers monitor effects at different doses and assess safety. During the five-year follow-up, participants will have regular assessments including eye scans to measure retinal thickness and damage areas, testing for the gene therapy product in eye fluid, and monitoring for any side effects or adverse events. The study team will also collect urine and tear samples to evaluate shedding of the therapy. Safety and eye health will be closely observed throughout the study to gather comprehensive data on the treatment's impact.
CONDITIONS
Brief Title
A First-in-Human, Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of Gene Therapy With TTX-381 for the Ocular Manifestations Associated With Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Has biallelic CLN2 mutations.
- Has decreased leukocyte TPP1 activity.
- Has clinical signs or symptoms consistent with CLN2 disease or an older sibling with confirmed CLN2 diagnosis.
- Is currently receiving biweekly intracerebroventricular enzyme replacement therapy with cerliponase alfa.
- Meets baseline disease condition: CRT ≤210 µm and ≤140 µm in both eyes, age ≤84 months.
- Is willing to adhere to the protocol and 5-year visit schedule.
- Sexually active females of childbearing potential or fertile males must agree to use medically accepted contraception from screening until 6 weeks after treatment.
- Was previously administered TTX-381 and met criteria at that time, with recommendation for enrollment by an independent committee.
You will not qualify if you...
- Any ocular or systemic condition that prevents treatment or study evaluation, such as severe lens or corneal opacities, glaucoma, or retinal abnormalities.
- Difference in screening CRT measurement between eyes greater than 10 µm.
- Prior severe hypersensitivity reactions to cerliponase alfa.
- Contraindications to intracerebroventricular cerliponase alfa, including device issues or infections.
- Prior participation in gene therapy studies, except compassionate use under approval.
- Prior participation in ocular clinical trials except limited cerliponase alfa injections with washout.
- Prior intraocular injections except limited cerliponase alfa injections or compassionate use.
- Participation in nonocular investigational drug study in past 6 months except cerliponase alfa.
- Ocular surgery within 6 months except for compassionate use administration.
- Prior bone marrow transplant.
- Use of certain medications in 30 days before treatment.
- Known sensitivities to peri-operative medications.
- Contraindications to systemic immunosuppression.
- Severe renal or hepatic insufficiency.
- Mutations in other CLN genes or genes related to inherited retinal disease.
- Contraindications to intraocular surgery.
- Positive pregnancy test at screening.
- Conditions preventing completion of follow-up or unsuitable for study.
- Recent positive COVID-19 test or persistent symptoms.
AI-Screening
AI-Powered Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Duration - Single administration with follow-up over 5 years
Participants receive a one-time subretinal dose of gene therapy (TTX-381) in the study eye. The other eye serves as a control.
Initial treatment visit followed by regular follow-up visits over 5 years
Trial Site Locations
Total: 2 locations
1
University Medical Center Hamburg-Eppendorf (UKE)- Childrens Hospital
Hamburg, Germany
Actively Recruiting
2
Greater Ormond Street Hospital
London, United Kingdom, Wc1N 3JH
Actively Recruiting
Research Team
T
Tern Therapeutics Patient Advocacy
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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