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

NCT05791864 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: TTX-381-11022021-000173-92
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a first-in-human, open-label, single ascending dose study of TTX-381 for the treatment of ocular manifestations of CLN2 (Batten disease).

Conditions

Neuronal Ceroid Lipofuscinosis Type 2

Keywords

CLN2; Batten Disease; Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Ocular and overall AE and SAEs through Day 360

  To evaluate the safety and tolerability of TTX-381 through Day 360 in participants with Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) disease

  360 days

Secondary Outcomes (4)

• To evaluate the effect of TTX-381 on area of EZ loss

  Day 180, Day 360

• To evaluate the effect of TTX-381 on central subfield photoreceptor layer thickness

  Day 180, Day 360

• To measure TTX-381 transgene product (tripeptidyl peptidase 1 [TPP1]) in aqueous humor

  Day 90, Day 360

• To evaluate shedding of TTX-381 in urine and tears

  Day 360

Study Arms (3)

Cohort 1: Main Treatment Arm

EXPERIMENTAL

2×10\^10 GC/eye

Genetic: TTX-381

Cohort 2: Main Treatment Arm

EXPERIMENTAL

6×10\^10 GC/eye

Genetic: TTX-381

Expansion Cohort

EXPERIMENTAL

Expansion cohort, dose level 2×10\^10 GC/eye as determined by Independent Data Monitoring Committee.

Genetic: TTX-381

Interventions

TTX-381 GENETIC

One time subretinal dose in study eye

Also known as: Gene Therapy (AAV9.CB7.hCLN2)

Cohort 1: Main Treatment Arm; Cohort 2: Main Treatment Arm; Expansion Cohort

Eligibility Criteria

• Age: 12 Months - 84 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• A participant is eligible to be included in the study only if all of the following criteria apply:
• Has biallelic CLN2 mutations.
• Has decreased leukocyte TPP1 activity.
• Has clinical signs or symptoms consistent with CLN2 disease (eg, developmental delay, developmental decline, seizure, vision loss, or other signs/symptoms) OR an older sibling with confirmed CLN2 diagnosis.
• Is currently receiving biweekly ICV ERT treatment with cerliponase alfa.
• Meets the following baseline disease condition according to age and CRT as assessed by SD-OCT and confirmed by CRC:
• Participants in the phase of accelerated decline in CRT:
• CRT at baseline ≤210 μm and
• CRT at baseline ≥140 μm in both eyes and
• Age ≤84 months,
• Is willing to adhere to the protocol and 5-year visit schedule.
• Sexually active female participants of childbearing potential (following menarche) or fertile male participants (following puberty) must be willing to use a medically accepted form of contraception from Screening Visit 2 until 6 weeks after vector administration.
• Was previously administered TTX-381.
• Upon retrospective review, met the above criteria at the time of administration of TTX-381. IDMC may consider exceptions to this when weighing whether to retrospectively enroll a participant who has received TTX-381.
• Has been recommended for enrollment into the clinical trial by IDMC

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Any ocular or systemic condition that, in the opinion of the investigator, would prevent administration and evaluation of the investigational product or interpretation of participant safety or study results (eg, significant lens or corneal opacities, glaucoma, amblyopia, gross retinal anatomical abnormality, etc).
• Difference in screening CRT measurement between the right and left eye \>10μm.
• Prior Grade 3 or 4 hypersensitivity reaction, eg, bronchospasm and hypotension requiring intravenous treatment, cardiac dysfunction, anaphylaxis to ICV cerliponase alfa infusion.
• Any other contraindication to the administration of ICV cerliponase alfa, including ventriculo-peritoneal shunt, acute intracerebroventricular access device leakage, device failure, or device-related infection that would impact ability to receive ICV cerliponase alfa.
• Prior participation in a gene therapy study. A subject who has received subretinal TTX-381 under a compassionate use protocol may be enrolled if the PI, Medical Monitor, and Sponsor all agree that he/she can safely and successfully participate in the study and the IDMC has approved their enrollment.
• 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, with the following two exceptions. A subject who has received a maximum of 3 intravitreal injections of cerliponase alfa may be enrolled in the study if 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. A subject who has received subretinal TTX-381 under a compassionate use protocol may be enrolled if the PI, Medical Monitor, and Sponsor all agree that he/she can safely and successfully participate in the study and the IDMC has approved their enrollment.
• Participation in a nonocular clinical study with an investigational drug in the past 6 months prior to screening, except for intracerebroventricular cerliponase alfa.
• Ocular surgery within the prior 6 months except as above for subretinal TTX-381 administration.
• 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 (not including asthma indications), flupirtine.
• 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. If the laboratory determines that the creatinine level is less than the lower limit of assay validation or detection, then the lowest limit cutoff value will be used to estimate eGFR.
• 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.

Sponsors & Collaborators

• Tern Therapeutics, LLC: lead

Study Sites (2)

University Medical Center Hamburg-Eppendorf (UKE)- Childrens Hospital

Hamburg, Germany

RECRUITING

Greater Ormond Street Hospital

London, Wc1N 3JH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neuronal Ceroid-Lipofuscinoses

Interventions

Genetic Therapy

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Engineering; Genetic Techniques; Investigative Techniques

Central Study Contacts

Tern Therapeutics Patient Advocacy

CONTACT

202-644-8488; patientadvocacy@terntx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: In order to minimize the effect of potential bias, wherever possible, endpoints will be measured or interpreted by masked evaluators.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2023
• First Posted: March 30, 2023
• Study Start: May 17, 2023
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2031
• Last Updated: December 18, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); DE (1)