A First-in-Human Study in Pediatric Patients With Ocular CLN2 Disease

Phase 1

Active, not recruiting

• Conditions: Neuronal Ceroid Lipofuscinosis Type 2
• Interventions: Genetic: RGX-381

• Registration Number: NCT05791864
• Lead Sponsor: Tern Therapeutics, LLC

Brief Summary

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

Detailed Description

This is a first-in-human, open-label, single ascending dose study of RGX-381, a gene therapy for the potential treatment of ocular manifestations of CLN2 (Batten disease). RGX-381 is being studied as a potential treatment of ocular manifestations of 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 working in their bodies. Without enough TPP1, cells cannot break down certain molecules in the body, so these storage materials build up and start to hurt the body, particularly the central nervous system (the brain and spine) and retinal cells (eyes); cause seizures; and change how children with CLN2 disease grow, act, think, and see. After eligibility has been confirmed, the participant's eyes will be assigned as the treated eye and the control fellow eye. Due to the symmetry in the clinical course of CLN2 ocular disease, untreated fellow eyes will serve as controls for the contralateral, treated eyes. Participants will be followed in this study for up to 5 years after RGX-381 administration.

Study Timeline

• Study First Submitted: 2023-03-17
• Study First Submitted QC: 2023-03-17
• Study First Posted: 2023-03-30
• Study Start: 2023-05-17
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-02
• Last Update Posted: 2024-12-04
• Primary Completion: 2026-07-30
• Study Completion: 2029-07-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

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 baseline disease condition according to age, retinal thickness, and visual acuity criteria ( varies by treatment arm)

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Exclusion Criteria

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).
• Prior participation in a gene therapy study
• Prior participation in another ocular clinical trial, except an intravitreal cerliponase alfa trial where a subject has received a maximum of 3 injections
• Prior intraocular injections of any kind, except an intravitreal cerliponase alfa trial where a subject has received a maximum of 3 injections
• Participation in a clinical study with an investigational drug in the past six months prior to screening, except for intracerebroventricular cerliponase alfa.
• Ocular surgery within the prior six months.
• Known sensitivity or contraindications to medications planned for use in the peri-operative period.
• Contraindications to systemic immunosuppression
• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Expansion Cohort: Late Treatment Arm	RGX-381	Dose level to be determined based on Independent Data Monitoring Committee review.
Cohort 2: Main Treatment Arm	RGX-381	6×10\^10 GC/eye
Cohort 1: Main Treatment Arm	RGX-381	2×10\^10 GC/eye
Expansion Cohort: Early Treatment Arm	RGX-381	Dose level to be determined based on Independent Data Monitoring Committee review.
Expansion Cohort: Main Treatment Arm	RGX-381	Dose level to be determined based on Independent Data Monitoring Committee review.

Primary Outcome Measures

Name	Time	Method
Safety: Number of participants with ocular and overall AE and SAEs	360 days	To evaluate the safety and tolerability of RGX-381 through Day 360 in participants with CLN2 disease
Safety: Change in SD-OCT measures and appearance of retinal layers over-time	360 days	To assess retinal structural changes with SD-OCT

Secondary Outcome Measures

Name	Time	Method
Safety: Evaluation of Long-Term Safety of RGX-381	5 years	Incidence of ocular AEs and SAEs post administration
Pharmacodynamics: TPP1 Expression	360 days	To assess TPP1 Expression as measured in Aqueous Humor

Trial Locations

Locations (1)

Greater Ormond Street Hospital; 🇬🇧 London, United Kingdom