Neuronal Ceroid Lipofuscinosis Type 2Phase 1/2NCT05791864
A Registrational Study of TTX-381 to Treat Vision Loss in CLN2 Disease
A Phase 1/2 study testing TTX-381 in people with Neuronal Ceroid Lipofuscinosis Type 2, run by Tern Therapeutics, LLC at 2 sites in 2 countries.
Trial summary
This is a registrational, first-in-human, open-label, dose escalation and expansion study evaluating the safety, tolerability and effectiveness of TTX-381, administered by injection under the retina, for the treatment of eye problems caused by CLN2 (Batten disease). Read more about this study
- Who is it for?
- Ages 24 to 84 months
- Conditions the study is for
- Neuronal Ceroid Lipofuscinosis Type 2
- What is being tested?
- TTX-381
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 17 May 2023to Dec 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 84 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participants must meet all of the following criteria:
- Biallelic CLN2 mutations.
- Decreased leukocyte TPP1 activity.
- Clinical signs or symptoms consistent with CLN2 disease, such as developmental delay or decline, seizures, vision loss, or an older sibling with confirmed CLN2 diagnosis.
- Currently receiving biweekly ICV ERT treatment with cerliponase alfa.
- Age ≥24 month and ≤84 months at screening
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- In the phase of accelerated decline in CRT with the following baseline retinal criteria confirmed by the central reading center:
- CRT ≤210 μm and
- CRT ≥140 μm in both eyes and
- Is willing and able to comply with the protocol and 5-year visit schedule.
- Written informed consent must be provided by the participants parent(s) or legally authorized representative(s)
Who cannot join
- Participants will be excluded if any of the following criteria apply:
- Any ocular or systemic condition that, in the investigator's opinion, would prevent administration or evaluation of TTX-381, interfere with interpretation of participant safety or study results or make the participant unsuitable for the study. (eg, significant lens or corneal opacities, glaucoma, amblyopia, gross retinal anatomical abnormality, etc).
- Difference in CRT measurement between the right and left eye >10μm at screening
- Prior Grade 3 or 4 hypersensitivity reaction, to ICV cerliponase alfa infusion. (eg, bronchospasm and hypotension requiring intravenous treatment, cardiac dysfunction, anaphylaxis)
- Any contraindication that would prevent continued administration of ICV cerliponase alfa, including ventriculo-peritoneal shunt, acute intracerebroventricular access device leakage, device failure, or device-related infection.
- Prior participation in a gene therapy study.
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- Prior participation in another ocular clinical trial, except an intravitreal cerliponase alfa trial where a subject has received a maximum of 3 injections and the PI, Medical Monitor, and Sponsor all agree that he/she can safely and successfully participate in the study after a washout period of 3 or more months.
- Prior intraocular injections of any kind, except prior treatment with an maximum of 3 ICV injections of cerliponase alfa if at least 3 months have passed since last injection.
- Participation in a nonocular clinical study with an investigational drug within 6 months prior to screening, except for intracerebroventricular cerliponase alfa.
- Ocular surgery within 6 months prior to screening.
- Prior bone marrow transplant.
- Use of the following medications within the 30 days prior to treatment: gemfibrozil, mycophenolate, prednisone or other steroids for the intended purpose of treating NCL (Steroid treatment for asthma is not excluded),
- Known sensitivity or contraindications to medications planned for use in the peri-operative period.
- Contraindications to systemic immunosuppression.
- Severe renal insufficiency as determined by an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, based on creatinine, at Screening
- Severe hepatic insufficiency as determined by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) or total bilirubin > 1.5 × ULN at Screening Visit 1, unless the subject has a previously known history of Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin < 35% of total bilirubin.
- Mutations in another CLN gene.
- Mutation in another gene associated with inherited retinal disease.
- Contraindications to intraocular surgery (eg, severe coagulopathy).
- Positive urine pregnancy test at Screening (applying only to females of childbearing potential).
- Any other condition that would not allow the potential participant to complete follow-up examinations during the study or, in the opinion of the investigator, makes the potential participant unsuitable for the study.
- The participant had a positive polymerase chain reaction (PCR) viral test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2 PCR) within the last 4 weeks before signing the informed consent form (ICF) or has persistent coronavirus disease (COVID-19) symptoms regardless of when the last SARS-CoV2 PCR viral test was performed or when the infection occurred.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Germany1 site, 1 recruiting
- Recruiting
University Medical Center Hamburg-Eppendorf (UKE)- Childrens Hospital
Hamburg
Prof. Dr. med. Angela Schulz, +49 (0)40 7410-20440, ncl-sprechstunde@uke.de
Prof. Dr. med. Angela Schulz
United Kingdom1 site, 1 recruiting
- Recruiting
Greater Ormond Street Hospital
London, Wc1N 3JH
research.ophthalmology@gosh.nhs.uk
Robert Henderson, MD
About this study
Official 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
This is a registrational, first-in-human, open-label, dose escalation and expansion study evaluating the safety, tolerability and effectiveness of TTX-381, administered by injection under the retina, for the treatment of eye problems caused by CLN2 (Batten disease). The study includes dose escalation and expansion groups evaluating treatment in one or both eyes. Participants are followed for 5 years after treatment to assess safety and clinical outcomes.
Read the detailed description
This is a registrational, first-in-human, open-label, dose escalation and expansion study of TTX-381, a gene therapy for the potential treatment of ocular manifestations of CLN2 (Batten disease). TTX-381 is being studied as a potential treatment for the eye and vision problems associated with neuronal ceroid lipofuscinosis type 2 (CLN2) disease.
Children with CLN2 disease have a non-working gene (set of instructions) that causes an enzyme called tripeptidyl-peptidase 1 (TPP1) to be missing or not work properly in their bodies. Without enough TPP1, cells cannot break down certain materials, causing them to build up and damage cells, particularly the central nervous system (the brain and spine) and retina (eyes). This can lead to seizures, changes in development and thinking and vision loss.
The study includes dose-escalation and expansion cohorts evaluating treatment in one or both eyes. In participants receiving treatment in one eye, the untreated fellow eye serves as the control because CLN2-related eye disease progresses similarly in both eyes. In the bilateral treatment cohort, both eyes receive TTX-381.
Participants will be followed in this study for 5 years after TTX-381 administration.
- Conditions
- Neuronal Ceroid Lipofuscinosis Type 2
- Being tested
- TTX-381
- Keywords
- CLN2, Batten Disease, Gene Therapy, Adeno-associated virus, AAV
- Medical subject headings
- Neuronal Ceroid-Lipofuscinoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTX-381Genetic
Gene Therapy (AAV9.CB7.hCLN2): One time subretinal dose in study eye
TTX-381Genetic
Gene Therapy (AAV9.CB7.hCLN2): One time subretinal dose in each eye
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Dose Level 1 | Experimental | 2×10^10 GC/eye Receives: Genetic: TTX-381 |
| Cohort 2: Dose Level 2 | Experimental | 6×10^10 GC/eye Receives: Genetic: TTX-381 |
| Cohort 3: Expansion Cohort | Experimental | 2×10^10 GC/eye Receives: Genetic: TTX-381 |
| Cohort 4: Bilateral Administration | Experimental | 2×10^10 GC/eye administered once per eye Receives: Genetic: TTX-381 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of TTX-381 through Day 360
Safety and tolerability will be assessed based on ocular and systemic adverse events and serious adverse events following administration of TTX-381.- ALL REGIONS
Measured: 360 days
Rate of change in area of Ellipsoid Zone (EZ) loss through Day 180
The rate of change in area of EZ loss will be assessed using spectral-domain optical coherence tomography (SD-OCT). - US
Measured: Day 180
Secondary outcomes (5)
Area of EZ Loss at Day 180 and Day 360
To evaluate the effect of TTX-381 on area of EZ loss as measured by SD-OCT- UK/EU
Measured: Day 180, Day 360
Central subfield photoreceptor layer thickness
To evaluate the effect of TTX-381 on central subfield photoreceptor layer thickness as measured by SD-OCT; Day 180- UK/EU and Day 360- All Regions
Measured: Day 180, Day 360
TTX-381 transgene product (tripeptidyl peptidase 1 [TPP1]) Aqueous Humor (AH) Concentration ≤78 ng/ml
The proportion of treated eyes with TPP1 concentration in aqueous humor greater than or equal to 78 ng/mL will be assessed. - US
Measured: Day 90
TTX-381 transgene product (tripeptidyl peptidase 1 [TPP1]) Aqueous Humor (AH) Concentration
TTX-381 transgene product (tripeptidyl peptidase 1 [TPP1]) will be measured in aqueous humor. - UK/EU
Measured: Day 90 & Day 360
Vector Shedding
To evaluate shedding of TTX-381 in urine and tears Secondary- UK/EU Exploratory-US
Measured: Day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2023
- Study start17 May 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuronal Ceroid Lipofuscinosis Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Participants are enrolled sequentially into dose-escalation and expansion cohorts. Cohorts 1 and 2 evaluate unilateral administration of TTX-381 at different dose levels. Cohort 3 is an expansion cohort evaluating unilateral administration at the selected dose, and Cohort 4 evaluates bilateral administration of TTX-381. Progression between cohorts is based on protocol-defined safety review and study milestones.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tern Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05791864
- Sponsor's protocol ID
- TTX-381-1102
- Other IDs
- 2025-521175-31-00, 2021-000173-92, 2025
- Status last verified
- Oct 2026
- First submitted
- 17 Mar 2023
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT05791864
- Acronym / sponsor ID
- TTX-381-1102
- Conditions
- Neuronal Ceroid Lipofuscinosis Type 2
- Keywords
- CLN2, Batten Disease, Gene Therapy, Adeno-associated virus, AAV
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Tern Therapeutics, LLCIndustry (pharma, biotech, devices)
- Study start
- 17 May 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 30 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a registrational, first-in-human, open-label, dose escalation and expansion study evaluating the safety, tolerability and effectiveness of TTX-381, administered by injection under the retina, for the treatment of eye problems caused by CLN2 (Batten disease). The study includes dose escalation and expansion groups evaluating treatment in one or both eyes. Participants are followed for 5 years after treatment to assess safety and clinical outcomes.
Detailed description
This is a registrational, first-in-human, open-label, dose escalation and expansion study of TTX-381, a gene therapy for the potential treatment of ocular manifestations of CLN2 (Batten disease). TTX-381 is being studied as a potential treatment for the eye and vision problems associated with neuronal ceroid lipofuscinosis type 2 (CLN2) disease.
Children with CLN2 disease have a non-working gene (set of instructions) that causes an enzyme called tripeptidyl-peptidase 1 (TPP1) to be missing or not work properly in their bodies. Without enough TPP1, cells cannot break down certain materials, causing them to build up and damage cells, particularly the central nervous system (the brain and spine) and retina (eyes). This can lead to seizures, changes in development and thinking and vision loss.
The study includes dose-escalation and expansion cohorts evaluating treatment in one or both eyes. In participants receiving treatment in one eye, the untreated fellow eye serves as the control because CLN2-related eye disease progresses similarly in both eyes. In the bilateral treatment cohort, both eyes receive TTX-381.
Participants will be followed in this study for 5 years after TTX-381 administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- Participants are enrolled sequentially into dose-escalation and expansion cohorts. Cohorts 1 and 2 evaluate unilateral administration of TTX-381 at different dose levels. Cohort 3 is an expansion cohort evaluating unilateral administration at the selected dose, and Cohort 4 evaluates bilateral administration of TTX-381. Progression between cohorts is based on protocol-defined safety review and study milestones.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Dose Level 1 | Experimental | Genetic: TTX-3812×10^10 GC/eye |
| Cohort 2: Dose Level 2 | Experimental | Genetic: TTX-3816×10^10 GC/eye |
| Cohort 3: Expansion Cohort | Experimental | Genetic: TTX-3812×10^10 GC/eye |
| Cohort 4: Bilateral Administration | Experimental | Genetic: TTX-3812×10^10 GC/eye administered once per eye |
Who may qualify
- Ages
- 24 to 84 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Biallelic CLN2 mutations.
- Decreased leukocyte TPP1 activity.
- Clinical signs or symptoms consistent with CLN2 disease, such as developmental delay or decline, seizures, vision loss, or an older sibling with confirmed CLN2 diagnosis.
- Currently receiving biweekly ICV ERT treatment with cerliponase alfa.
- Age ≥24 month and ≤84 months at screening
Key exclusion criteria (22 listed)
- Any ocular or systemic condition that, in the investigator's opinion, would prevent administration or evaluation of TTX-381, interfere with interpretation of participant safety or study results or make the participant unsuitable for the study. (eg, significant lens or corneal opacities, glaucoma, amblyopia, gross retinal anatomical abnormality, etc).
- Difference in CRT measurement between the right and left eye >10μm at screening
- Prior Grade 3 or 4 hypersensitivity reaction, to ICV cerliponase alfa infusion. (eg, bronchospasm and hypotension requiring intravenous treatment, cardiac dysfunction, anaphylaxis)
- Any contraindication that would prevent continued administration of ICV cerliponase alfa, including ventriculo-peritoneal shunt, acute intracerebroventricular access device leakage, device failure, or device-related infection.
- Prior participation in a gene therapy study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TTX-381Gene Therapy (AAV9.CB7.hCLN2): One time subretinal dose in study eye | Genetic | Cohort 1: Dose Level 1, Cohort 2: Dose Level 2, Cohort 3: Expansion Cohort |
| TTX-381Gene Therapy (AAV9.CB7.hCLN2): One time subretinal dose in each eye | Genetic | Cohort 4: Bilateral Administration |
Primary outcome
Safety and tolerability of TTX-381 through Day 360
Time frame: 360 days
Safety and tolerability will be assessed based on ocular and systemic adverse events and serious adverse events following administration of TTX-381.- ALL REGIONS
Rate of change in area of Ellipsoid Zone (EZ) loss through Day 180
Time frame: Day 180
The rate of change in area of EZ loss will be assessed using spectral-domain optical coherence tomography (SD-OCT). - US
5 secondary outcomes
Area of EZ Loss at Day 180 and Day 360
Time frame: Day 180, Day 360
Central subfield photoreceptor layer thickness
Time frame: Day 180, Day 360
TTX-381 transgene product (tripeptidyl peptidase 1 [TPP1]) Aqueous Humor (AH) Concentration ≤78 ng/ml
Time frame: Day 90
TTX-381 transgene product (tripeptidyl peptidase 1 [TPP1]) Aqueous Humor (AH) Concentration
Time frame: Day 90 & Day 360
Vector Shedding
Time frame: Day 360
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TTX-381 in people with Neuronal Ceroid Lipofuscinosis Type 2, run by Tern Therapeutics, LLC at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tern Therapeutics Patient Advocacy (202-644-8488, patientadvocacy@terntx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of TTX-381 through Day 360 (time frame: 360 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.